Objective: This paper aims to discuss the mechanism of actions, pathways, and metabolites triggered due to the development of neuropathy and nephropathy post-long-haul diabetes in patients. The therapeutic targets are also highlighted, proving to be a potential cure for such conditions.

Methods: Research works were searched from international and national databases with keywords like “diabetes,” “diabetic nephropathy,” “NADPH,” “oxidative stress,” “PKC,” “Molecular mechanisms,” “ cellular mechanisms,” “complications of diabetes,” and “factors.” The databases searched were PubMed, Scopus, Directory of open access journals, Semantic Scholar, Core, Europe PMC, EMBASE, Nutrition, FSTA- Food Science and Technology, Merck Index, Google Scholar, PubMed, Science Open, MedlinePlus, Indian citation index, World Wide Science, and Shodhganga.

Results: Pathways causing protein kinase C (PKC) activation, free radical injury, oxidative stress, and aggravating the conditions of neuropathy and nephropathy were discussed. In diabetic neuropathy and nephropathy, neurons and nephrons are affected to the extent that their normal physiology is disturbed, thus leading to further complications and conditions of loss of nerve sensation in diabetic neuropathy and kidney failure in diabetic nephropathy.

Current treatment options available for the management of diabetic neuropathy are anticonvulsants, antidepressants, and topical medications, including capsaicin. According to AAN guidelines, pregabalin is recommended as the first line of therapy, whereas other drugs currently used for treatment are gabapentin, venlafaxine, opioids, amitriptyline, and valproate.

Drug targets for treating diabetic neuropathy must suppress the activated polyol pathways, kinase C, hexosamine, and other pathways, which amplify neuroinflammation. Targeted therapy must focus on the reduction of oxidative stress and proinflammatory cytokines and suppression of neuroinflammation, NF-κB, AP-1, etc.

Conclusion: Potential drug targets must be considered for new research on the treatment of neuropathy and nephropathy conditions.]]> https://www.benthamscience.comarticle/129597Background: This study was performed to evaluate the protective effects of chrysin (CH) on metabolic impairment and pancreatic injury caused by sub-chronic chlorpyrifos (CPF) intoxication in male rats.

Methods: Forty male Wistar rats were randomly allocated into five groups (n=8). Intraperitoneal injections of chrysin (12.5, 25 and 50 mg/kg for 45 days) and CPF (10 mg/kg for 45 days) gavage were performed. Present findings indicated that the serum levels of glucose, total cholesterol, and lowdensity lipoprotein-cholesterol, as well as body weight, were increased in the CPF-exposed group.

Results: It was also found that CPF decreased superoxide dismutase activity as well as increased malondialdehyde and nitric oxide levels in the pancreatic tissue of exposed animals. Histopathological examination also confirmed the toxic effects of CPF on pancreatic tissue as mostly evidenced by infiltration of inflammatory cells and necrosis. CH (50 mg/kg) decreased blood glucose concentration (p < 0.05), TG (p < 0.05), and LDL-C in CPF-exposed animals. CH decreased the pancreas levels of MDA in all treated CPF-exposed groups versus the non-treated CPF-exposed group (p < 0.05, p < 0.001, p < 0.001, respectively). A significant difference was not seen in the NO and MDA levels and SOD activity between CH-treated (50 mg/kg) animals exposed to CPF and controls. A significant difference was not seen in the NO and MDA levels and SOD activity between CHtreated (50 mg/kg) animals exposed to CPF and controls.

Conclusion: A significant difference was not seen in the NO and MDA levels and SOD activity between CH-treated (50 mg/kg) animals exposed to CPF and controls. In conclusion, CH could prevent initiate and progress of CPF-induced metabolic impairment by modulating oxidative stress in pancreatic tissue as a target organ of organophosphorus pesticides.

Objective: The objective of this study is to present hepatic metastasis of GIST and GEP-NET with Diffusion weighted MR imaging(DWI) and the Apparent diffusion coefficients (ADC) values of masses.

Methods: 18 GIST patients and 8 GEP-NET patients were examined retrospectively. 11 males and 6 females were present in GIST group, 7 males to 5 females were involved in GEP-NET group. 18 primary GIST and 10 hepatic metastasis of GIST, 8 original GEP-NET and 19 hepatic metastasis of GEP-NET; total 55 GIST and GEP-NET masses were analysed by ADC mapping. MR images were acquired by 1,5 T MR units (32 mT/min gradient strength- Achieva; Philips Healthcare, Best, Netherlands and 32 channel GE Signa GE-Wisconsin-USA); by using a 4-8 channel standard phased-array torso XL coil, all images were evaluated by an Abdominal MRI experienced radiologist. DWI was performed in the transverse plane by using spin-echo-planar imaging sequence.

Results: No statistical differences were observed between GIST and GEP-NET patients according to age and gender variations. No significant statistical differences were observed according to the diameters and ADC values of GIST and GEP-NET patients. A significant statistical difference was observed between GIST and GEP-NET groups in terms of size of liver metastasis which was significantly higher in GIST patients. All three groups (GIST_Hep. MET, GEP-NET_Liver_Met and normal) were statistically differed according to ADC values. With the ROC curve analysis: Hepatic metastasis of GIST(n=10) and normal liver (n:47) had cut-off value for ADC: 0.925 under AUC: 0.939 with regard to ADC values and regarded 89.4% Sensitivity, 100% Specificity, 100% PPV and 66.7% PPV. ROC curve of GEP NET_ Hepatic metastasis (n=19) group and normal liver (n:47) group presented cut-off value for ADC: 0.860 under AUC: 0.967 correlated to ADC values with 93.6% sensitivity, 89.5% specificity, 95.7% PPV and 85% PPV.

Conclusion: High cellular tumors resulted from liver metastasis of GIST and GEP-NET’s, and a positive correlation was observed between ADC values and cellularity/differentiation ratios of metastatic masses.

Objective: Here, we give a comprehensive overview of this quickly developing theranostic application that includes all relevant imaging, diagnostic, therapeutic, and monitoring elements for the management of diabetes and diabetes neuropathy.

Methods: The data for the current study was gathered by searching PubMed and Google Scholar. Several research and review publications from various publishers, including Springer Nature, Bentham Science, PLOS one, MDPI, and ACS Publishing Centre, were evaluated to compile the data.

Result: Recent developments in theranostics have shown promise as alternate management approaches for diabetes and ailments linked to diabetes. Numerous nanotechnology-built biosensors, including multiwalled carbon nanotubes, copper nanowires, zinc oxide tetrapods, and nanoparticle- embedded contact lenses, offer benefits in monitoring diabetic neuropathy.

Conclusion: The potency, usability, and dependability of insulin substitutes have been demonstrated by a variety of innovative methods for the management of diabetes, which includes nanotechnology approaches using Gene-Based Nanoparticles (siRNA), Liposomes, Exosomes/ Extracellular Vesicles, Neuromodulation, and Inhalable Nanoparticles. Over the past few years, the development of various theranostic nanoparticles for Diabetic neuropathy has experienced an unprecedented expansion. Even though much work needs to be done to precisely evaluate the genuine benefits provided by these particles, such as issues with nanotoxicity, theranostic nanoparticles will have a significant impact on the field of nanomedicine.

Objective: The study aimed to develop and evaluate baicalein-loaded aquasomes for improving solubility and comparing their antidiabetic properties to acarbose through in silico docking.

Methods: Baicalein-loaded aquasomes were prepared through a three-step process: core preparation, lactose coating, and drug loading. The evaluation included assessing particle size, drug-excipient interactions, drug entrapment efficiency, loading capacity, in vitro drug release, and the kinetics of drug release. In silico docking and in vitro α-amylase inhibition activity was evaluated to assess the anti-diabetic potential of baicalein.

Results: The baicalein-loaded aquasomes were spherical with sizes ranging from 300-400 nm. FTIR analysis indicated no interaction between the components. The formulation exhibited drug entrapment efficiency of 94.04±0 4.01% and drug loading of 17.60 ± 01.03%. Drug release study showed sustained and complete (97.30 ± 02.06%) release, following first-order kinetics. Docking analysis revealed comparable binding affinity to acarbose, while the α-amylase inhibition assay showed greater inhibition potential of the aquasomes compared to the baicalein solution.

Conclusion: Aquasomes offer an alternative approach to conventional delivery methods. The selfassembling characteristics of aquasomes greatly simplify their preparation process, adding to their appeal as a drug delivery system.

Objectives: The objective of this review was to relate the consumption of probiotic bacteria and its effects on inflammatory diseases, including obesity, type II diabetes and celiac disease.

Methods: A search was carried out in English, between the years 2011 and 2022, for research articles and clinical trials with humans and in vivo studies. Research showed improvement in cardiovascular risk markers, and improvement in insulin sensitivity, lipid profile and plasma atherogenic index, in obesity with the use of probiotics. In type II diabetes, decreased levels of fasting glucose, glycated hemoglobin, insulin and glycemic index, and increased levels of peptide 1, superoxide dismutase and glutathione peroxidase were observed.

Results: In addition to cellular protection of the islets of Langerhans and positive alteration of TNF- α and IL-1β markers. Improvement in the condition of patients with celiac disease was observed, since the neutralization of the imbalance in serotonin levels was observed, reducing the expression of genes of interest and also, a decrease in cytokines.

Conclusion: Therefore, the use of probiotics should be encouraged.

In conclusion, the gut microbiome is a critical player in maintaining human health, and its modulation by herbal medicines is a burgeoning area of research. Understanding the complex interactions between herbal compounds and gut microbiota will pave the way for innovative approaches to personalized healthcare and the development of herbal-based therapeutics aimed at promoting gut health and overall well-being.

Objective: The present study aims to enhance understanding of the disease mechanism and its progression by identifying prognostic biomarkers, potential drug targets, and candidate drugs that can be used for therapy in pancreatic cancer.

Methods: Gene expression profiles from the GEO database were analyzed to identify reliable prognostic markers and potential drug targets. The disease's molecular mechanism and biological pathways were studied by investigating gene ontologies, KEGG pathways, and survival analysis to understand the strong prognostic power of key DEGs. FDA-approved anti-cancer drugs were screened through cell line databases, and docking studies were performed to identify drugs with high affinity for ARNTL2 and PIK3C2A. Molecular dynamic simulations of drug targets ARNTL2 and PIK3C2A in their native state and complex with nilotinib were carried out for 100 ns to validate their therapeutic potential in PDAC.

Results: Differentially expressed genes that are crucial regulators, including SUN1, PSMG3, PIK3C2A, SCRN1, and TRIAP1, were identified. Nilotinib as a candidate drug was screened using sensitivity analysis on CCLE and GDSC pancreatic cancer cell lines. Molecular dynamics simulations revealed the underlying mechanism of the binding of nilotinib with ARNTL2 and PIK3C2A and the dynamic perturbations. It validated nilotinib as a promising drug for pancreatic cancer.

Conclusion: This study accounts for prognostic markers, drug targets, and repurposed anti-cancer drugs to highlight their usefulness for translational research on developing novel therapies. Our results revealed potential and prospective clinical applications in drug targets ARNTL2, EGFR, and PI3KC2A for pancreatic cancer therapy.

Methods: A retrospective cohort study was conducted in 108 hospitalized Type 2 diabetes (T2D) patients with renal injury, including 70 with DKD and 38 with NDKD (non-DKD). Clinical features, pathological findings, and follow-up parameters were collected. Serum and urine FABP4 were detected by ELISA. An immunohistochemistry stain was used to determine FABP4 in renal tubulointerstitium. A double immunofluorescence stain was employed to assess FABP4- and CD68-positive macrophages. Correlation analysis, logistic regression models, receiver operating characteristic (ROC), and Kaplan-Meier survival curve were performed for statistical analysis.

Results: DKD patients had increased expression of FABP4 and ectopic fat deposition in tubules. As shown by correlation analyses, FABP4 expression in renal tubules was positively correlated with UNAG (r=0.589, p=0.044) and ESRD (r=0.740, p=0.004). Multivariate regression analysis revealed that UNAG level was correlated with FABP4 expression level above median value (odds ratio:1.154, 95% confidence interval:1.009-1.321, p=0.037). High-expression of FABP4 in renal tubules of DKD was at an increased risk of ESRD. Increased FABP4 expression in inflammatory cells was also associated with ESRD in DKD.

Conclusion: High-expression of FABP4 is involved in the pathogenesis of renal tubular lipid injury and is a risk factor for poor prognosis in DKD patients.

Objective: The aim of the review is to categorize and summarize the available information on phytochemicals and pharmacological properties of Costus pictus D. Don and suggest outlooks for future research.

Methods: This review combined scientific data regarding the use of Costus pictus D. Don plant for the management of diabetes and other ailments. A systematic search was performed on Costus pictus plant with anti-diabetic, anti-cancer, anti-microbial, anti-oxidant, and other pharmacological properties using several search engines such as Google Scholar, PubMed, Science Direct, Sci-Finder, other online journals and books for detailed analysis.

Results: Research data compilation and critical review of the information would be beneficial for further exploration of its pharmacological and phytochemical aspects and, consequently, new drug development. Bioactivity-guided fractionation, isolation, and purification of new chemical entities from the plant as well as pharmacological evaluation of the same will lead to the search for safe and effective novel drugs for better healthcare.

Conclusion: This review critically summarizes the reports on natural compounds, and different extract of Costus pictus D. Don with their potent anti-diabetic activity along with other pharmacological activity. Since this review has been presented in a very interactive manner showing the geographical region of availability, parts of plant used, mechanism of action and phytoconstituents in different extracts of Costus pictus responsible for particular action, it will be of great importance to the interested readers to focus on the development of the new drug leads for the treatment of diseases.

Aims: The present study aimed to investigate the influence of delayed or missed dosages on sirolimus pharmacokinetics (PK) in pediatric tuberous sclerosis complex (TSC) patients and to recommend remedial dosages for nonadherent patients.

Methods: A published sirolimus population PK model in pediatric TSC patients was used to assess the influence of different nonadherence scenarios and recommend optimally remedial dosages based on Monte Carlo simulation. Thirteen nonadherent scenarios were simulated in this study, including delayed 2h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 23.5 h, and missed one dosage. Remedial dosing strategies contained 10-200% of scheduled dosages. The optimal remedial dosage was that with the maximum probability of returning the individual therapeutic range.

Results: For delayed or missed sirolimus dosages in pediatric TSC patients, when the delayed time was 0-8 h, 8-10 h, 10-18 h, 18-22.7 h, 22.7-24 h, 70%, 60%, 40%, 30%, 20% scheduled dosages were recommended to take immediately. When one dosage was missed, 120% of scheduled dosages were recommended at the next dose.

Conclusion: It was the first time to recommend remedial dosages for delayed or missed sirolimus therapy caused by poor medication compliance in pediatric TSC patients based on Monte Carlo simulation. Meanwhile, the present study provided a potential solution for delayed or missed dosages in clinical practice.

Methodology: The cells were transfected in vitro by both constructed IGF-I AS and IGF-I TH expression episomal vectors; part of these cells was co-cultured with plant phytochemicals, modulating IGF-I expression. Both AS and TH approaches completely suppressed IGF-I expression and induced MHC-1 / B7 immunogenicity related to the IGF-I receptor signal.

Results: This immunogenicity proved to be stronger in IGF-I TH than in IGF-I AS-prepared cell vaccines, especially in TH / phytochemical cells. The AS and TH vaccines generated an important TCD8+ and TCD8+CD11b- immune response in treated GBM patients and increased the median survival of patients up to 17-18 months, particularly using TH vaccines; in some cases, 2- and 3-year survival was reported. These clinical results were compared with those obtained in therapies targeting other growth factors.

Conclusion: The anti-gene IGF-I vaccines continue to be applied in current GBM personalized medicine. Technical improvements in the preparation of AS and TH vaccines to increase MHC-1 and B7 immunogenicity have, in parallel, allowed to increase in the median survival of patients.

Objective: In this work, we aimed to summarize the interesting results from preclinical and clinical studies that assessed the effects of natural alkaloids (berberine, nigelladine A, piperine, trigonelline, capsaicin, nuciferine, evodiamine, mahanine, and magnoflorine) on impaired insulin sensitivity and worsened insulin resistance, which play a pivotal role in the pathogenesis of type 2 diabetes.

Methods: In the current review, PubMed, ScienceDirect, Springer, and Google Scholar databases were used. The inclusion criteria were based on the following keywords and phrases: insulin sensitivity, insulin resistance, alkaloids and insulin resistance, alkaloids and type 2 diabetes, mechanisms of action, and alkaloids.

Results: The outcomes reported in this review demonstrated that the selected alkaloids increased insulin sensitivity and reduced insulin resistance in vitro and in vivo evidence, as well as in clinical trials, through improving insulin-signaling transduction mainly in hepatocytes, myocytes, and adipocytes, both at cellular and molecular levels. Insulin signaling components (InsR, IRS-1, PI3K, Akt, etc.), protein kinases and phosphatases, receptors, ion channels, cytokines, adipokines, and microRNAs, are influenced by alkaloids at transcriptional and translational levels, also in terms of function (activity and/or phosphorylation). Multiple perturbations associated with insulin resistance, such as ectopic lipid accumulation, inflammation, ER stress, oxidative stress, mitochondrial dysfunction, gut microbiota dysbiosis, and β-cell failure, are reversed after treatment with alkaloids. Furthermore, various indices and tests are employed to assess insulin resistance, including the Matsuda index, insulin sensitivity index (ISI), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT), which are all enhanced by alkaloids. These improvements extend to fasting blood glucose, fasting insulin, and HbA1c levels as well. Additionally, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Homeostasis Model Assessment of β-cell function (HOMA-β) are recognized as robust markers of insulin sensitivity and β-cell function, and it is noteworthy that alkaloids also lead to improvements in these two markers.

Conclusion: Based on the findings of the current review, alkaloids may serve as both preventive and curative agents for metabolic disorders, specifically type 2 diabetes. Nonetheless, there is an urgent need for additional clinical trials to explore the potential benefits of alkaloids in both healthy individuals and those with type 2 diabetes. Additionally, it is crucial to assess any possible side effects and interactions with antidiabetic drugs.

Case Presentation: We present the case of a 59-year-old non-diabetic man with a 2-month history of severe and recurrent fasting hypoglycaemia presenting with severe dyspnea and sweating. Further workup revealed low insulin, C-peptide, and IGF-1 levels and a large right in-trathoracic solitary fibrous tumor. Unfortunately, bioassays for IGF-2 were unavailable at our hos-pital. Nevertheless, as hypoglycemia completely resolved after resection of the mass, Doege-Potter syndrome was highly suspected.

Conclusion: Doege-Potter syndrome is a complication of rare tumors. If hy-poglycemia is unexplained, this syndrome should always be suspected, and the presence of un-known masses should be investigated.

Objective: In this study, for the first time, the impacts of 2-(α-naphthoyl) ethyltrimethylammonium iodide (α- NETA), an antagonist of CMKLR1, adipose-derived stem cells (ADSCs), and their combinations on metabolic and endocrine aberrancies were assessed in the WAT and ovarian tissues of the letrozole (LET)-induced PCOS rats.

Methods: In the current study, 30 Wistar rats were randomly divided into five groups: control (n = 6), LET-induced PCOS (1.5 mg/kg p.o., n = 6), LET + ADSCs (10⁶ ADSCs i.v., n = 6), LET + α-NETA (10 mg/kg p.o., n = 6), and LET + ADSCs + α-NETA (n = 6). The blood samples and adipose and ovarian tissues were obtained to evaluate the effects of ADSCs and α-NETA on hormonal and metabolic parameters in the PCOS rats.

Results: Our findings showed that the administration of α-NETA, ADSCs, and the combination of both favorably restored the irregular estrus cycle and considerably modulated the endocrine parameters in PCOS rats. In addition, these therapeutic factors remarkably regulated steroidogenic and adipogenic gene expressions, as well as the genes related to glucose metabolism and brown adipose tissue (BAT) markers in these animals.

Conclusion: These findings indicate that the combination of ADSCs and α-NETA can successfully ameliorate metabolic and endocrine dysfunction in LET-induced PCOS rats, and this strategy could be a new therapeutic choice for patients with PCOS.

Objective: To analyze pathophysiological characteristics/co-morbidities precipitating myocardial ischemia in patients with HTN LVH and provide a rationale for recommending beta-blockers (BBs) to prevent/treat ischemia in LVH.

Methods: We searched PubMed, SCOPUS, PubMed, Elsevier, Springer Verlag, and Google Scholar for review articles and guidelines on hypertension from 01/01/2000 until 01/05/2022. The search was limited to publications written in English.

Results: HTN LVH worsens ischemia in coronary artery disease (CAD) patients. Even without obstructive CAD, several pathophysiological mechanisms in HTN LVH can lead to myocardial ischemia. In the same guidelines that recommend BBs for patients with HTN and CAD, we could not find a single recommendation for BBs in patients with HTN LVH but without proven CAD. There are several reasons for the proposal of using some BBs to control ischemia in patients with HTN and LVH (even in the absence of obstructive CAD).

Conclusion: Some BBs ought to be considered to prevent/treat ischemia in patients with HTN LVH (even in the absence of obstructive CAD). Furthermore, LVH and ischemic events are important causes of ventricular tachycardia, ventricular fibrillation, and sudden cardiac death; these events are another reason for recommending certain BBs for HTN LVH.

Objective: The purpose of this study was to investigate the effect of Genipin on osteosarcoma and its potential mechanism of action.

Methods: Crystal violet staining, MTT assay and colony formation assay were used to detect the effect of genipin on the proliferation of osteosarcoma. The effects of vitexin on migration and invasion of osteosarcoma were detected by scratch healing assay and transwell assay. Hoechst staining and flow cytometry were used to detect the effect of genipin on apoptosis of osteosarcoma cells. The expression of related proteins was detected by Western blot. An orthotopic tumorigenic animal model was used to verify the effect of genipin on osteosarcoma in vivo.

Results: The results of crystal violet staining, MTT method and colony formation method proved that genipin significantly inhibited the proliferation of osteosarcoma cells. The results of the scratch healing assay and transwell assay showed that gen significantly inhibited the migration and invasion of osteosarcoma cells. The results of Hoechst staining and flow cytometry showed that genipin significantly promoted the apoptosis of osteosarcoma cells. The results of animal experiments show that genipin has the same anti-tumor effect in vivo. Genipin may inhibit the growth of osteosarcoma through PI3K/AKT signaling.

Conclusion: Genipin can inhibit the growth of human osteosarcoma cells, and its mechanism may be related to the regulation of PI3K/AKT signaling pathway.

Introduction: The overarching goal of diabetic research and treatment has always been to restore insulin independence and an average blood glucose level. Chemotherapeutic antidiabetic agents can manage diabetes but often show toxicity and drug resistance. Natural phytomedicines may be useful along with stem cell therapy for diabetes management. Even if the whole pancreatic organ and islet transplantation, are becoming benchmark techniques for diabetes management and control, a considerable scarcity of eligible donors of pancreatic tissues and organs severely limits their use. Stem cell treatment provides a bunch of possibilities for treating people with diabetes.

Methods: For this purpose, comprehensive article searching was conducted, with relevant material obtained using search engines such as Scopus, PubMed, MEDLINE, Google, and others, using appropriate keywords.

Results: Stem cell therapies, including induced pluripotent stem cells and mesenchymal stem cells, are now becoming a popular area of investigation. Recent advancements in stem cell therapy might provide a feasible treatment option. Furthermore, in recent years, some novel bioactive compounds derived from plants have demonstrated antidiabetic action with higher potency than oral hypoglycaemic medications. Recent regenerative medicine and stem cell treatment advancements might subsequently provide a feasible diabetic management option. On the other hand, medicinal herbs have been considered a better choice for the extensive treatment of diabetes.

Conclusion: If proper attention is not given to control diabetes by antidiabetic chemotherapeutic agents, natural phytomedicine, and sophisticated treatment like stem cell therapy, then the lifespan of patients will be decreased, and some associated secondary problems will also arise. So, the present review attempts to discuss naturopathy as an alternative resource in combination with stem cell therapy for the progressive management of diabetes and associated disorders.

Objective: This study aimed to investigate the role of the SIRT1/Nrf2/ARE signaling pathway in the effect of resveratrol on the hydrogen peroxide-induced injury of rat ovarian granulosa-lutein cells.

Methods: In this study, ovarian granulosa-lutein cells extracted from 3-week female SD rats were treated with 200 μM H₂O₂ in the presence or absence of 20 μM resveratrol. siRNA-SIRT1 and siRNA-Nrf2 were used to inhibit the expression of SIRT1 and Nrf2, respectively. Cell counting kit 8 (CCK-8), cellular morphology, progesterone secretion, and estradiol were used to evaluate cell injury. Hoechst 33258 staining was used to measure cell apoptosis. DHE staining, DCFH-DA staining, malondialdehyde content, protein carbonyl content, total antioxidant capacity and SOD viability were used to estimate the levels of oxidative stress. Western blot analysis was used to detect the levels of apoptosis-related proteins, and SIRT1/Nrf2/ARE signaling pathway-related proteins.

Results: The H₂O₂ treatment-induced rat ovarian granulosa-lutein cells injury was shown as decreased cell viability, impaired cellular morphology, and decreased levels of progesterone and estradiol. The H₂O₂ treatment also exacerbated cell apoptosis demonstrated as more apoptotic cells stained by Hoechst staining, decreased level of anti-apoptosis protein Bcl-2 and increased level of pro-apoptosis protein Bax. These effects of cell injury and apoptosis induced by H₂O₂ can be ameliorated by resveratrol. Resveratrol also alleviated oxidative stress induced by H₂O₂, supported by decreased superoxide anion and cellular total ROS, decreased malondialdehyde and protein carbonyl levels, and increased total antioxidant capacity and SOD viability. Western blot results demonstrated resveratrol reversed the H₂O₂-induced decrease in levels of antioxidant enzymes containing ARE sequences and activated SIRT1/Nrf2 pathway. Further treatment by siRNA-Nrf2 suggested resveratrol could not activate the expression of antioxidant enzymes under a condition of inhibition of Nrf2.

Conclusion: This study demonstrates that resveratrol attenuated oxidative stress to protect H₂O₂-induced rat ovarian granulosa-lutein cell injury and apoptosis via SIRT1/Nrf2/ARE signaling pathway.

Aim: This case-control study aimed to assess the role of HLA-DP-rs3077 (A/G) and HLA-DQrs3920 (A/G) polymorphism in T1DM.

Subjects and Methods: This study enrolled 400 individuals: 200 patients with T1DM and 200 ageand sex-matched healthy controls. Hemoglobin A1C and random, fasting, and postprandial blood sugar levels were determined for all subjects. Genotypic and allelic distributions of HLA-DPrs3077 (A/G) and HLA-DQrs3920 (A/G) SNPs were determined using real-time polymerase chain reaction (PCR).

Results: Frequency of the HLA-DPrs3077A allele was high among the diabetic group (91.3%); however, the difference was non-significant [OR (95% C.I) = 1.422(0.89-2.252), P=0.098]. The frequency of the HLA-DQrs3920 GG genotype was higher in control than the diabetic group (52.5% vs.12%), whereas that of the AA genotype was higher in the person with diabetes than in the control group (34% vs.4%). Individuals carrying the HLA-DQrs3920A allele were 4.5 times more likely to have T1DM than those carrying the G allele [OR (95% C.I) = 4.510 (3.338- 6.094), P<0.001*]. The presence of HLA-DPrs3077A and HLA-DQ rs3920A in the same person increases T1DM risk by 3.6 times that of G allele [OR (95%C.I) = 3.608(2.173-5.991), P<0.001*].

Conclusion: HLA-DPrs3077 and HLA-DQrs3920 SNPs have a role in T1DM as the coexistence of HLA-DPrs3077A and HLA-DQrs3920A alleles increases the risk.

Objective: Anti-aging and antiwrinkle agents are in demand for maintaining skin tone. Seed oils composed of polyunsaturated fatty acids are traditionally used in cosmetic products as moisturizers and emollients, while palmitic acid and oleic acid are known for their penetration-enhancing effect. With the changing trend for extraction of oils like cold pressed methods, seed oils enriched with polyphenols, flavonoids, carotenoids, and phytosterols are good antioxidants and antimicrobials and therefore have an ever-growing demand for their usage in the treatment of skin diseases. In this review, an attempt will be made to brief the phytoconstituents present in various seed oils and their utilization against skin ailments. Furthermore, a mechanistic approach towards the benefit of oils in skin barrier repair, antiaging, and photo-aging with the help of extensive well-designed clinical trials carried out in the recent past is elaborated.

Methods: A literature search in the Scopus database, Pubmed, and Medline was carried out using the terminology “aging, photoaging, antioxidant, UV-protection, sunscreens, skin barrier repair, and fatty acids, formulations” in the study. Data were retrieved over the last twenty years.

Results: The review summarises the mechanistic approach and beneficial application of seed oils for healthy and glowing skin. The oils obtained from olives, sesame, borage, grape seeds, and carrot seeds have multitargeted effects. However, the variation in pharmacological effect may vary based on geographically differing varieties, skin type, and person-to-person variation. The need to standardize the varieties for their phytoactive ingredients and the composition of formulation used for skin care can help utilize the seeds as a potential source of actives against skin diseases.

Conclusion: The potential of seed oils can be increased with appropriate analytical tools, validation protocols, and systematic experimental studies at preclinical and clinical trials for their application to skin care products.

The relevant aspects of chemistry and biochemistry and the importance of copper compounds in medicine give us a comprehensive knowledge of the multifaceted applications of copper in physiology and physiopathology.

In this review, we present an outline of the chemistry, and the antitumor properties of copper complexes on breast, colon, and lung cancer cells focus on the role of copper in cancer, the relationship between structure-activity, molecular targets, and the study of the mechanism of action involved in its anticancer activity. This overview is expected to contribute to understanding the design, synthesis, and uses of copper complexes as antitumor agents in the most common cancers.

The mammalian target of rapamycin (mTOR) is a l signalling protein with critical functions in cell growth, metabolism, and proliferation. It is known for its regulatory functions in protein synthesis and angiogenesis cascades. The structure of mTOR consists of two distinct complexes (mTORC1 and mTORC2) with diverse functions at different levels of the signalling pathway. By activating mRNA translation, the mTORC1 plays a key role in regulating protein synthesis and cellular growth. On the other hand, the functions of mTORC2 are mainly associated with cell proliferation and survival.

By using an appropriate inhibitor at the right time, mTOR modulation could provide immunosuppressive opportunities as antirejection regimens in organ transplantation as well as in the treatment of autoimmune diseases and solid tumours. The mTOR also has an important role in the inflammatory process. Inhibitors of mTOR might indeed be promising agents in the treatment of viral infections. They have further been successfully used in patients with severe influenza A/H1N1 pneumonia and acute respiratory failure. The officially accepted mTOR inhibitors that have undergone clinical testing are sirolimus, everolimus, temsirolimus, and tacrolimus. Thus, further studies on mTOR inhibitors for SARS-CoV-2 infection or COVID-19 therapy are well merited.

Objective: The purpose of this study was to examine the altered expression of miRNAs and their target genes in placental tissue (PL), cord blood (CB), and maternal blood (MB) of matched non-glucose tolerant (NGT) and GDM mother.

Methods: In a case-control study, micro-RNA was quantified from forty-five serum (MB n = 15, CB n = 15, and PL n = 15) and matched placental tissue using stem-loop RT-qPCR followed by target prediction, network construction and functional and pathways enrichment analysis. Further, target genes were verified in-vitro through transfection and RT-qPCR.

Results: Five miRNAs, namely hsa-let 7a-5P, hsa-miR7-5P, hsa-miR9-5P, hsa-miR18a-5P, and hsamiR23a- 3P were significantly over-expressed (p < 0.05) in all three samples namely PL, CB, and MB of GDM patients. However, the sample-wise comparison reveals higher expression of miRNA 7 in MB while lowest in CB than control. Furthermore, a comparison of fold change expression of target genes discloses a lower expression of IRS1, IRS2, and RAF1 in MB while comparatively higher expression of NRAS in MB and CB. In-vitro validation reveals lower expression of IRS1/2 and RAF1 in response to overexpression of miR-7 and vice-versa. Thus it is evident that increased miRNA7 expression causes down-regulation of its target genes IRS1, IRS2, and RAF1 in GDM mother compared to control. Further, target prediction, pathway enrichment, and hormone analysis (significantly higher FSH & LH in MB of GDM compared to NGT) revealed insulin signaling, inflammatory and GnRH signaling as major pathways regulated by miRNA7.

Conclusion: Thus, an elevated level of miRNA7 may be associated with the progression of GDM by altering the multiple pathways like insulin, GnRH, and inflammatory signaling pathways via targeting IRS1, IRS2, and RAF1, implicating a new therapeutic target for GDM.

This paper aims to summarize the molecular mechanisms of the potential natural compounds on improving NAFLD, thus providing a direction and basis for further research on the pathogenesis of NAFLD and the development of effective drugs for the prevention and treatment of NAFLD.

By searching various online databases, such as Web of Science, SciFinder, PubMed, and CNKI, NAFLD and these natural compounds were used as the keywords for detailed literature retrieval.

The pathogenesis of NAFLD and the molecular mechanisms of the potential natural compounds on improving NAFLD have been reviewed.

Many natural compounds from traditional Chinese medicine have a good prospect in the treatment of NAFLD, which can serve as a direction for the development of anti-NAFLD drugs in the future.

Methods: The research results associated with lncRNA H19 and diabetes mellitus are collected and summarized on PubMed.

Conclusion: LncRNA H19 is a potential instructive marker for the treatment of diabetes mellitus and diabetic complications.

Objective: Recent studies have shown that high glucose can significantly up-regulate the expression of the TXNIP. Overexpression of TXNIP in β-cells not only induced apoptosis but also decreased the production of insulin. At the same time, TXNIP deficiency protected the apoptosis of β-cells, leading to increased insulin production. Therefore, finding small molecules that can modulate TXNIP expression and downstream signalling pathways is essential. Thus, the inhibition of TXNIP has beneficial effects on the cardiovascular system and other tissues such as the heart and the kidney in DM. Therefore, DM treatment must target small TXNIP activity, inhibit expression, and promote endogenous cell mass and insulin production.

Conclusion: This review briefly describes the effect mechanism, regulatory mechanism, and crystal structure of TXNIP. In addition, we highlight how TXNIP signalling networks contribute to diabetes and interact with drugs that inhibit the development often and its complexes. Finally, the current status and prospects of TXNIP targeted therapy are also discussed.

Background: Eugenol is a major polyphenolic component of Ocimum sanctum (Tulsi) which attributes wide pharmacological activities and can serve as a biomarker. However, the possible effect of eugenol on longevity in Caenorhabditis elegans has not been reported.

Objective: The objective of this investigation was to provide the first scientific based results about the effect of eugenol on longevity, slowing down of paralysis in Alzheimer’s model and the mechanism behind it in Caenorhabditis elegans animal model system.

Methods: The phenolic components of methanolic extract of Ocimum sanctum were analyzed by RP-HPLC. Worms were exposed to different concentrations of extract and one of its components - eugenol. Lifespan, health span, survival in CL4176 Alzheimer’s model and molecular mechanism were analyzed.

Results: Extract of Ocimum sanctum and eugenol increased lifespan and provided indemnity against pro-oxidants. It also significantly improved healthy ageing and slowed the progression of neurodegeneration in CL4176 Alzheimer’s model of the worm by increasing survival against prooxidants and slowing down the paralysis. Longevity effect was independent of the DAF-16 as observed by using DAF-16::GFP and daf-16 null mutant strains. These results implicate eugenol as a potent therapeutic compound that may curtail ageing and age related disorders like- Alzheimer’s disease.

Conclusion: The present work demonstrated eugenol as a potential anti-ageing compound that may curtail ageing, improve heath span by enhancing resistance to oxidative stress and exerts its effect independent of DAF-16 pathway. So, it can be assumed that eugenol can be beneficial to humans as well, albeit further research is necessary before declaring it for human consumption.

Objectives: Owing to the present remarkable anti-diabetic effects with no or few side effects of lipids, the aim of this study was to assess the state-of-the-art research on anti-diabetic effects of lipids via the modulation of angiogenesis.

Methods: To study the effects of lipids in diabetes via modulation of angiogenesis, we have searched the electronic databases including Scopus, PubMed, and Cochrane.

Results: The promising anti-diabetic effects of lipids were reported in several studies. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil (FO) were reported to significantly induce neovasculogenesis in high glucose (HG)-mediated endothelial progenitor cells (EPCs) with neovasculogenesis dysfunction in type 2 diabetic mice. Linoleic acid, mono-epoxy-tocotrienol- α (MeT3α), and ginsenoside Rg1 facilitate wound closure and vessel formation. N-Palmitoylethanolamine (PEA), α-linolenic acid (ALA), omega-3 (ω3) lipids from flaxseed (FS) oil, ω-3 polyunsaturated fatty acids (PUFA), lipoic acid, taurine, and zeaxanthin (Zx) are effective in diabetic retinopathy via suppression of angiogenesis. Lysophosphatidic acid, alkyl-glycerophosphate, crocin, arjunolic acid, α-lipoic acid, and FS oil are involved in the management of diabetes and its cardiac complications. Furthermore, in two clinical trials, R-(+)-lipoic acid (RLA) in combination with hyperbaric oxygenation therapy (HBOT) for treatment of chronic wound healing in DM patients, as well as supplementation with DHA plus antioxidants along with intravitreal ranibizumab were investigated for its effects on diabetic macular edema.

Conclusion: Proof-of-concept studies presented here seem to well shed light on the anti-diabetic effects of lipids via modulation of angiogenesis.

Methods: In this study, a consecutive administration of rhReg4 was applied to normal Sprague- Dawley rats or rats after OA induction. Histological changes and chondrocyte proliferation in the articular cartilage were measured.

Results: We found that RhReg4 promotes chondrocyte proliferation in normal rats, and RhReg4 attenuated the severity of OA in rats by promoting chondrocytes’ proliferation in OA rats.

Conclusion: In conclusion, recombinant human regenerating gene 4 (rhReg4) attenuates the severity of osteoarthritis in OA animal models and may be used as a new method for the treatment of osteoarthritis.

Methodology: A thorough literature study was performed using scientific databases, like PubMed, Science Direct, Scopus, and Web of Science, for determining the design of the study, and each article was checked for citation and referred to formulate the present review article.

Conclusion: Nanotechnology can be applied in the food processing industry to control the unregulated use of food additives and intervene in the biochemical mechanisms at a cellular and physiological level for ensuring the safety of food products. The prospective of nano-additive of chemical origin could be useful to reduce risks of hazards related to human health that are caused majorly due to the invasion of food contaminants (either intentional or non-intentional) into food, though this area still needs scientific validation. Therefore, this review provides comprehensive knowledge on different facets of food contaminants and also serves as a platform of ideas for encountering health risk problems about the design of improved versions of nano-additives.

Result: On the basis of their sources, stem cells can be classified as adult or embryonic stem (ES) cells. Physiologically, the ES cells have the capability to differentiate into all body cells and develop into the normal adult organism, whereas adult stem cells serve as a repair system by restoring damaged tissues of the body. The adult stem cells referred to as Mesenchymal stem cells (MSCs) can be derived from various adult body organs, whereas embryos give rise to embryonic stem cells. MSCs possess the unique property of proliferation, trans-differentiation, and secretion of important biomolecules to create a microenvironment, which is immunosuppressive and stimulates native MSCs of damaged tissue. MSCs being immunocompromised cells can be used in autologous as well as in allogenic mode.

Conclusion: In veterinary therapeutics, MSCs equipped with engineering and pharmaceutical modifications are offered as potential candidates in the treatment of wound healing, nerve injury, bone/ligament injury, etc., and also bear a great hope for the improvement of udder health and milk production in animals.]]> https://www.benthamscience.comarticle/113310 Objective: To determine the effects of curcumin on the liver protein profile of diabetic db/db mice.

Methods: db/db and Wild Type (WT) male mice were allocated in four groups, and they were fed for eight weeks. Three WT and three diabetic db/db mice received a Standard Diet (SD; WT and db/db groups, respectively); three WT and three diabetic db/db mice received a SD supplemented with 0.75% (w/w) curcumin (WT+C and db/db+C groups, respectively). Liver proteins were separated by 2D electrophoresis. Differential protein expression analysis was performed on Image- Master 2D Platinum software, and selected proteins were identified by MALDI-TOF-MS and subjected to enrichment analysis using STRING and DAVID databases.

Results: Thirty-six proteins with differential expression due to diabetic background and curcumin treatment were found; these proteins participate in the metabolism of amino acids, carbohydrates, and lipids. Interestingly, the altered expression of seven proteins was prevented in the liver of the diabetic mice that received curcumin.

Conclusion: Among all differentially expressed proteins, curcumin reverted the altered expression of seven proteins. Thus, although it was observed that curcumin did not affect the biochemical parameters, it does modify the expression of some liver proteins in diabetic mice.]]> https://www.benthamscience.comarticle/114479 Among many misfolding protein conformations, self-assembly or aggregation is the most significant. It leads to the formation of highly oligomeric self-aggregates that precipitate and interfere with many biochemical processes with serious pathological consequences. The most common implication of protein aggregation leading to the formation of deposits / plaques of various morphological types is the onset of neurological and neurodegenerative diseases that include Alzheimer’s, Parkinson’s, Huntington, ALS (Amyotrophic Lateral Sclerosis), CJD (Creutzfeldt Jakob Dementia), Prion diseases, Amyloidosis and other forms of dementia. However, increasing studies have revealed that protein aggregation may also be associated with other diseases such as cancer, type 2 diabetes, renal, corneal and cardiovascular diseases. Protein aggregation diseases are now considered as part of “Proteinopathy” which refers to conditions where proteins become structurally abnormal or fail to fold into stable normal configurations. In this review, we reflect on various aspects of protein self-aggregation, potential underlying causes, mechanism, role of secondary structures, pathological consequences and possible intervention strategies as reported in published literature.]]> https://www.benthamscience.comarticle/119973Background: The pecan nutshell contains phytochemicals with various biological activities that are potentially useful in the prevention or treatment of diseases, such as cancer, diabetes, and metabolic imbalances associated with heart diseases.

Objective: The aim of this study is to update this topic by means of a literature review and include those studies that contribute to the knowledge of the chemical composition and biological activities of pecan nutshell, particularly those related to the therapeutic potential against some chronic degenerative diseases associated with oxidative stress.

Methods: Exhaustive and detailed review of the existing literature was conducted using electronic databases.

Conclusion: The pecan nutshell is a promising natural product with pharmaceutical uses in various diseases. However, additional research related to the assessment of efficient extraction methods and characterization, particularly the evaluation of the mechanisms of action in new in vivo models, is necessary to confirm these findings and development of new drugs with therapeutic use.

Methods: The isolated compounds have been identified by chemical methods and spectrometric analysis, such as UV, ¹H NMR, and ¹³C NMR spectroscopy. With regard to the anti-diabetic activity, a series of experiments have been carried out in vivo on Westar albino rats. Diabetes has been induced in animals by an intraperitoneal injection of streptozotocine. They have been treated with an aqueous extract from the aerial part of Pallenis spinosa (250 and 500 mg/kg body weight) and glibenclamide (5 mg/kg body weight) every day for 21 days.

Results: The chemical analysis of the aerial part of Pallenis spinosa led to the isolation of five known flavonoids, including patuletin 7-galactopyranoside, patuletin-3-O-α-L-rharnnopyranosyl (1-6)-β-D-galactopyranoside, tricin 7-glucopyranoside, tricin, and quercetin. The aqueous extract of both doses, 250 mg and 500 mg, has shown significant activity in reducing blood sugar, with 43.38% for the dose of 250 mg/kg and 37.76% for the dose of 500 mg/kg, as well as a significant decrease in the total fatness, triglycerides, and the total cholesterol levels in animals. The treatment was compared to the diabetes control group (p = 0.05). We used glibenclamide as a reference, and it showed similar results.

Conclusion: In order to explore and develop new anti-diabetic drugs, more studies are needed on this plant for scrutinizing its mechanism of activity.]]> https://www.benthamscience.comarticle/114789 https://www.benthamscience.comarticle/118204 https://www.benthamscience.comarticle/113172 Objective: The current study aimed to analyze the protective effects of metformin on streptozocin- induced diabetic rats in T1DM in hepatic tissues.

Methods: In the present study, male Wistar rats (n=24) were randomly assigned into 2 groups (n=12 for each control and test), and metformin (100 mg/kg/day) was given for 7 weeks. Afterward, diabetes was induced by streptozocin (STZ) at a single dose of 150 mg/kg. Blood glucose was examined daily before and after STZ induction. The animals were euthanized by cervical dislocation 5 days after streptozocin injection, after which liver and pancreas were harvested from each rat.

Results: The biochemical analyses revealed that metformin resulted in significantly reduced plasma glucose levels and higher pancreatic insulin levels in the test group. Using a restrictive cut-off of at least 2-FC and an adjusted p-value (q-value) of ≤0.05, a sum of 747 genes for the metformin group were shown to be differentially regulated compared to controls (320 Down and 427 Up), by which they were obtained from the liver. Furthermore, the evidence is attained that metformin may hinder the loss of critical β-cells by reducing inflammatory and apoptosis signaling, promoting fatty acid β-oxidation, and inducing metabolism.

Conclusion: Collectively, this study has demonstrated a decrease in blood glucose levels and a rise in insulin-levels and thus consequent prophylactic effects in metformin-given STZ-induced diabetic rats.]]> https://www.benthamscience.comarticle/116309 https://www.benthamscience.comarticle/115416 Objectives: Current research aimed to investigate the anti-diabetic and hepato-protective effect of green synthesized silver nanoparticles (ABAgNPs) using Ajuga bracteosa aqueous extract (ABaqu).

Methods: In vitro anti-diabetic and cytotoxic effects were carried out via α- glucosidase inhibition, brine shrimp lethality, and protein kinase inhibition assays. For in vivo screening of 200 mg/kg and 400 mg/kg of both ABAgNPs and ABaqu in alloxan-induced and CCl4-induced Swiss albino mice were used. Liver and kidney functional markers, hematology, and histopathological studies were carried out after 14 days of administration.

Results: In vivo antidiabetic and anti-cancerous effects showed valuable anti-hyperglycemic and hepatoprotective potential when mice were treated with ABaqu and ABAgNPs. A significant reduction in the blood glucose level was recorded when ABaqu and ABAgNPs were administrated orally compared to Glibenclamide treated group. Significant reduction in ALT, AST, ALP, urea, uric acid, and creatinine was recorded in ABaqu and ABAgNPs treated diabetic mice. The hepato-protective findings indicated that ALT, ALP, AST were elevated in CCl4-induced mice while declined in both ABAgNPs and ABaqu treated CCl4-induced mice. Histopathological examination revealed that ABAgNPs have hepato-protective activity.

Conclusion: It was concluded that ABAgNPs and ABaqu possessed strong anti-diabetic and hepatoprotective phytoconstituents, which could be used in the prevention of diseases.]]> https://www.benthamscience.comarticle/111966 https://www.benthamscience.comarticle/119079 https://www.benthamscience.comarticle/117824Background: All parts of Momordica charantia L. have potential hypoglycemic properties in reversing the metabolic disorder of diabetes mellitus. However, there exists a need for preparing an effective and safer formulation of active phytochemicals. We have also reviewed and analyzed certain patents on such preparatory methods for Momordica charantia L. formulations.

Objective: This study aimed to isolate essential oil from the seeds of Momordica charantia L., analyze its phytochemicals, and study their anti-diabetic effects.

Methods: The essential oil was isolated by the hydrodistillation method and analyzed for phytochemicals by GC-MS. Furthermore, its acute toxicity was tested in rats. Anti-diabetic effects were evaluated in Streptozotocin-induced diabetic rats with 17.5 and 55 mg/kg b.wt of essential oil by evaluating blood glucose, serum lipid profile, liver glycogen, protein, and other serum markers such as ALT, AST, ALP, urea, and creatinine. The histologic changes in the liver, pancreas, and kidney were evaluated using Haematoxylin and Eosin staining.

Results: The phytochemicals having hypoglycaemic and insulin induction potency were identified in the GC-MS analysis. A highly significant (p≤0.01; p≤0.001) reduction in blood glucose was observed from 17.5 mg/kg and 55 mg/kg essential oil treatments, respectively. Diabetes-associated metabolic alterations (p≤0.001) observed in diabetic control rats such as lipid profile, enzymes, glycogen, protein, urea, and creatinine were normalized upon treatment with essential oil. Moreover, the histologic changes in vital organs reversed in treated rats.

Conclusion: The essential oil of Momordica charantia L. seed has promising potency to normalize the metabolic changes of type II diabetes mellitus.

γ-AApeptides are able to mimic primary and secondary structures of therapeutic peptides, which make them promising candidates for molecular probes and potential drug leads. In the past decade, several interesting structures and applications of γ-AApeptides have been developed by different approaches such as structure-based design, combinatorial library screening, and peptides selfassembly and folding. By following the mechanism of host-defense peptides (HDPs), antibiotic γ- AApeptides showed broad-spectrum activity. At the same time, γ-AApeptides can be used for combinatorial library screening because of their structural stability and their chemodiversity. Anticancer agents, anti-T2DM (Type 2 diabetes mellitus) agents, anti-HIV (human immuno-deficiency virus) agents and anti-Alzheimer’s disease agents were developed by combinatorial screening and rational design. Furthermore, γ-AApeptides as biopolymers, nanomaterials, supramolecular structures and self-assembly architectures were studied due to their unique backbone structures. Therefore, γ-AApeptides may play an important role in the development of peptidomimetics.