Potential Therapeutic Effects Research Articles

Inhibitory Effect of Cayratia albifolia C. L. Li Extract on LPS-induced Inflammation of RAW264.7 Cells by Regulating the Nrf2/HO-1 Axis

Background: Cayratia albifolia C. L. Li (Jiao Mei Gu (JMG)) has potential therapeutic effects in inflammatory diseases. Purpose: The primary goal of the research was to focus on the antioxidant and anti-inflammatory qualities of C. albifolia and the underlying mechanisms that contribute to these benefits. Methods: To explore the anti-inflammatory abilities of JMG, we employed enzyme-linked immunosorbent assay and nitric oxide (NO) assay in a lipopolysaccharide (LPS)-induced macrophage inflammation model. Furthermore, flow cytometry was employed to assess the antioxidant effects of C. albifolia, and Western blotting was used to reveal the underlying mechanisms. Results: Ethyl acetate extract of C. albifolia effectively reduced the release of NO, interleukin-6, tumor necrosis factor-α, and prostaglandin E2 in macrophages. Additionally, it prevented the expression of reactive oxygen species. Mechanistically, the extract may downregulate the expression of inducible nitric oxide synthase, cyclooxygenase-2, the nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) protein expression. Conclusion: The ethyl acetate extract of C. albifolia demonstrated remarkable anti-inflammatory and antioxidant effects by modulating the Nrf2/HO-1 axis.

Antiviral Activity of Angelica Tenuissima Nakai against Influenza A Virus.

The influenza A virus poses a serious threat to human health and is an important global public health issue. The drugs currently used for treatment are becoming increasingly ineffective against influenza A viruses and require the development of new antiviral drugs. Angelica tenuissima Nakai (ATN), a traditional herbal medicine belonging to the Umbelliferae family, exhibits a broad range of pharmacological activities, including inflammation, headache, and cold symptoms. In the present study, based on target protein identification, functional enrichment analysis, and gene set comparisons, we first suggested that ATN has potential therapeutic effects against influenza A virus infection. Next, methylthiazol tetrazolium (MTT) and sulforhodamine B colorimetric (SRB) assay results revealed that ATN exhibited low cytotoxicity in Madin-Darby canine kidney (MDCK) cells. The antiviral properties of ATN were observed against H1N1 and H3N2 virus strains. Microscopy confirmed the increased survival rate of the host cells. Further time-of-addition experiments revealed that the addition of ATN before virus adsorption showed similar results to the whole period of treatment. The pre- and co-treated groups showed lower levels of viral RNA (M1 protein). The results of this study suggest that ATN exhibits antiviral properties against the influenza A virus. These therapeutic properties of ATN can serve as a theoretical basis for further research on the applicability of ATN in the development of antiviral agents.

Exploring Radioiodinated Anastrozole and Epirubicin as AKT1-Targeted Radiopharmaceuticals in Breast Cancer: In Silico Analysis and Potential Therapeutic Effect with Functional Nuclear Imagining Implications.

This study evaluates radio-iodinated anastrozole ([125I]anastrozole) and epirubicin ([125I]epirubicin) for AKT1-targeted breast cancer therapy, utilizing radiopharmaceutical therapy (RPT) for personalized treatment. Through molecular docking and dynamics simulations (200 ns), it investigates these compounds' binding affinities and mechanisms to the AKT1 enzyme, compared to the co-crystallized ligand, a known AKT1 inhibitor. Molecular docking results show that [125I]epirubicin has the highest ΔGbind (-11.84 kcal/mol), indicating a superior binding affinity compared to [125I] anastrozole (-10.68 kcal/mol) and the co-crystallized ligand (-9.53 kcal/mol). Molecular dynamics (MD) simulations confirmed a stable interaction with the AKT1 enzyme, with [125I]anastrozole and [125I]epirubicin reaching stability after approximately 68 ns with an average RMSD of around 2.2 Å, while the co-crystallized ligand stabilized at approximately 2.69 Å after 87 ns. RMSF analysis showed no significant shifts in residues or segments, with consistent patterns and differences of less than 2 Å, maintaining enzyme stability. The [125I]epirubicin complex maintained an average of four H-bonds, indicating strong and stable interactions, while [125I]anastrozole consistently formed three H-bonds. The average Rg values for both complexes were ~16.8 ± 0.1 Å, indicating no significant changes in the enzyme's compactness, thus preserving structural integrity. These analyses reveal stable binding and minimal structural perturbations, suggesting the high potential for AKT1 inhibition. MM-PBSA calculations confirm the potential of these radio-iodinated compounds as AKT1 inhibitors, with [125I]epirubicin exhibiting the most favorable binding energy (-23.57 ± 0.14 kcal/mol) compared to [125I]anastrozole (-20.03 ± 0.15 kcal/mol) and the co-crystallized ligand (-16.38 ± 0.14 kcal/mol), highlighting the significant role of electrostatic interactions in stabilizing the complex. The computational analysis shows [125I]anastrozole and [125I]epirubicin may play promising roles as AKT1 inhibitors, especially [125I]epirubicin for its high binding affinity and dynamic receptor interactions. These findings, supported by molecular docking scores and MM-PBSA binding energies, advocate for their potential superior inhibitory capability against the AKT1 enzyme. Nevertheless, it is crucial to validate these computational predictions through in vitro and in vivo studies to thoroughly evaluate the therapeutic potential and viability of these compounds for AKT1-targeted breast cancer treatment.

The Effect of Chlorogenic Acid on Methotrexate-Induced Oxidative Stress and Inflammation in Lung Tissue of Rats

Although methotrexate (MTX) is a widely used chemotherapeutic agent, lung toxicity remains a significant problem, limiting its use. The molecular mechanism of MTX-related lung toxicity is not fully understood. However, increased reactive oxygen species (ROS)-induced oxidative stress (OS) and inflammation play an important role in lung injury. Chlorogenic acid (CHA) is a natural phenolic compound that has been shown in recent years to have beneficial effects in many pathologies associated with OS and inflammation. This study focused on investigating for the first time, the potential therapeutic effects of CHA in the lung tissue of rats exposed to MTX. After lung toxicity was induced in rats by MTX (20 mg/kg) injection on the first day, two different doses of CHA (1.5 and 3 mg/kg) were used for treatment for 3 days. The results showed that CHA treatment reduced the level of pulmonary lipid peroxidation, inflammation, and apoptosis and promoted the pulmonary antioxidant system in rats subjected to MTX. Taken together, the antioxidant and anti-inflammatory properties of CHA may play a central role in attenuating MTX-induced lung injury, but the exact mechanism needs to be investigated in more extensive preclinical studies.

The Role of Claudins in the Pathogenesis of Dextran Sulfate Sodium-Induced Experimental Colitis: The Effects of Nobiletin.

The pathogenesis of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease is not well understood. This study investigated the roles and regulation of the claudin-1, -2, -3, and -4 isoforms in the pathogenesis of ulcerative colitis, and the potential therapeutic effects of nobiletin. Colitis was induced in rats by administering dextran sulfate sodium [DSS] in drinking water for seven days. Animals were treated daily with nobiletin [oral, 60 mg/Kg body weight] and studied in four groups, C [non-colitis control], D [DSS-induced colitis], CN [nobiletin-treated non-colitis control], and DN [nobiletin-treated DSS-induced colitis]. On day seven, the animals were sacrificed, and colonic tissues were collected and analyzed. Both macroscopic and microscopic findings suggest the progression of colitis. In the inflamed colon, claudin-1 and -4 proteins were decreased, claudin-2 increased, while the claudin-3 protein remained unchanged. Except for claudin-1, these changes were not paralleled by mRNA expression, indicating a complex regulatory mechanism. Uniform β-actin expression along with consistent quality and yield of total RNA indicated selectivity of these changes. Nobiletin treatment reversed these changes. Altered expression of the claudin isoforms -1, -2, and -4 disrupts tight junctions, exposing the lamina propria to microflora, leading to electrolyte disturbance and the development of ulcerative colitis. Nobiletin with its anti-inflammatory properties may be useful in IBD.

Sedative-Hypnotic Effect and Mechanism of Carbon Nanofiber Loaded with Essential Oils of Ligusticum chuanxiong (Ligusticum chuanxiong Hort.) and Finger Citron (Citrus medica L. var. sarcodactylis) on Mice Models of Insomnia.

(1) Background: Insomnia is a neurological illness that poses a significant threat to both physical and mental health. It results in the activation of neuroglial cells, heightened neuroinflammation, oxidative stress, and disruptions in the Hypothalamic-Pituitary-Adrenal (HPA) axis. Ligusticum Chuanxiong (CX) and Finger citron (FC) are frequently utilized botanicals for addressing sleeplessness. Both herbs possess notable anti-inflammatory properties in their volatile oils. However, their effectiveness is hindered by the nasal mucosal irritation and instability they exhibit. (2) Methods: This study involved the preparation of a nanofiber composite system using carbon nanofiber (CNF) suspensions containing essential oils of Ligusticum chuanxiong-Finger citron (CXEO-FCEO-CNF). The effects and mechanisms of these essential oils in improving insomnia were investigated using an insomnia mouse model after encapsulation. (3) Results: The CXEO-FCEO-CNF had an average particle size of 103.19 ± 1.64 nm. The encapsulation rates of essential oils of Ligusticum chuanxiong (CXEO) and essential oils of Finger citron (FCEO) were 44.50% and 46.15%, respectively. This resulted in a considerable improvement in the stability of the essential oils over a period of 30 days. The essential oils effectively decreased the irritation of the nasal mucosa following encapsulation. Furthermore, CXEO-FCEO-CNF enhanced voluntary activity and sleep in mice with insomnia, notably boosted the activity of superoxide dismutase (SOD), reduced the concentration of lipoxidized malondialdehyde (MDA), decreased the levels of hormones associated with the HPA axis, and regulated the levels of neurotransmitters, resulting in a beneficial therapeutic outcome. CXEO-FCEO-CNF contains a total of 23 active ingredients, such as alpha-Asarone, (E)-methyl isoeugenol, and Senkyunolide. These ingredients primarily work by modulating the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling system to decrease oxidative stress and inflammatory reactions. (4) Conclusions: This study presented initial evidence that the combination of CXEO and FCEO in nanofiber formulations effectively reduces the nasal mucosal irritation and instability of essential oils. Furthermore, it demonstrated the potential anti-neuroinflammatory and therapeutic effects of these formulations in treating insomnia. Overall, this study provides a theoretical foundation for developing new essential oil formulations derived from herbs.

Curry Leaf: Traditional Herb and its Medicinal Profile, Multipotential Nutraceutical Properties, Phytochemistry, and Pharmacological Activity

: This review briefly discusses about herbal medication, i.e., Murraya koenigii, also known as curry leaves, that have been useful in traditional medicine for centuries and natural products with different pharmacological activities. It might lead to a better knowledge of natural products' potential therapeutic effects and the creation of promising pharmaceuticals with minimal toxicity and great effectiveness for treating different ailments. The Chinese Biomedical Database (CBM), Technological Periodical Database (VIP), China National Knowledge Infrastructure (CNKI), Google Scholar, Elsevier, ScienceDirect, Sci Finder, and PubMed were used to compile the content of this review. From 1975 through 2020, data were collected. More than 23 components of M. koenigii have been discovered so far, with sterols, carbohydrates, flavonoids, and alkaloids causing the most concern. Due to its multicomponent nature, M. koenigii has a wide range of beneficial biological activities, including analgesic, anticancer, antioxidative, antimicrobial, antihypertensive, antidiabetic activities, antibacterial, and anti-inflammatory properties. This review discusses the vast details of M. koenigii (Curry leaves) and its possible medicinal use for different therapeutic purposes. The plant incorporates other essential substances, as discussed, are beneficial to remedy and deal with several ailment cures that exhibit different pharmacological actions. The accumulated ethnopharmacological details of that plant may be further helpful for the upcoming research about the said properties and use of M. koenigii.

Role of omega-3 fatty acids in reducing proteinuria: A systematic review and meta-analysis.

Proteinuria, a hallmark of renal and systemic disorders, is associated with adverse outcomes, especially in chronic kidney disease and cardiovascular disease. Omega-3 fatty acids have garnered attention for their cardiovascular benefits and potential therapeutic effects on proteinuria. This systematic review and meta-analysis aimed to evaluate the impact of omega-3 fatty acid supplementation on proteinuria levels across various kidney-related conditions. Studies published from 1989 to 2023 were systematically identified, including randomized controlled trials, cohort, case-control, and cross-sectional studies. Nine studies involving a total of 347 participants were included in the analysis. The meta-analysis revealed a neutral overall effect size of omega-3 fatty acid supplementation on proteinuria levels, assessed under both common and random effect models. Despite the lack of statistically significant evidence supporting the efficacy of omega-3 fatty acids in reducing proteinuria, the variability in interventions and patient populations suggests potential individual responses. The find-ings highlight the heterogeneity in responses to omega-3 fatty acid supplementation and emphasize the need for cautious interpretation. While no definitive conclusion can be drawn, the results underscore the importance of targeted research focusing on specific subgroups or conditions that may benefit from omega-3 supplementation. These findings contribute to the evolving understanding of personalized kidney health strategies and pave the way for further exploration and optimization of omega-3 fatty acids' therapeutic applications.

Cytotoxic and pro-oxidant profile of a photosensitive ruthenium nitrosyl candidate for NO delivery in healthy human fibroblasts.

Ruthenium nitrosyl (Ru-NO) complexes are of interest as photoactive nitric oxide (NO) donor candidates for local therapeutic applications. NO plays a crucial regulatory role in skin homeostasis, concentration-dependently affecting processes like the proliferation, apoptosis, autophagy and redox balance. In this context, we investigated HE-10, a ruthenium-based photoinducible NO donor, for its pro-oxidant and cytotoxic effects under light and dark conditions in VH10 human foreskin fibroblast cells. We also tested its intracellular and extracellular NO-releasing function. Our study reveals a significant dose-dependent cytotoxic effect of HE-10, an increase in intracellular reactive oxygen and nitrogen species, and the occurrence of apoptosis in skin fibroblast cells. Furthermore, exposure to both increasing doses of HE-10 and white LED light led to substantial cellular events, including a significant induction of autophagy and G2/M phase cell cycle arrest. Paradoxically, these effects were not solely attributable to NO release based on DAF2-DA NO probe results, suggesting that intracellular photochemical reactions additional to NO photolysis contribute to HE-10's biological activity. This study shows that HE-10 exhibits both cytotoxic and potential therapeutic effects, depending on concentration and light exposure. These findings are crucial for developing targeted Ru-NO complex treatments for skin diseases and potentially certain types of skin cancer, where controlled NO release could be beneficial.

A Systematic Review of the Benefits of Physical Exercise on Mental Health and Quality of Life in Patients With Substance Use Disorders.

Physical exercise is increasingly recognized for its potential therapeutic effects in individuals with substance use disorders (SUDs), particularly in terms of relapse prevention, mental health improvement, and enhanced quality of life (QoL). This systematic review aimed to statistically summarize findings from numerous randomized controlled trials (RCTs) on the effects of physical exercise on mental health outcomes, QoL, abstinence-related outcomes, and cravings among SUD patients. A systematic search was conducted across PubMed, Web of Science, and Scopus databases, resulting in the inclusion of 15 studies, comprising RCTs, cohort studies, observational studies, and quasi-experimental designs. The review revealed a significant reduction in stress and depression, with a standardized mean difference (SMD) of 0.63, indicating a moderate effect size. Patients engaging in physical exercise reported a higher QoL across various domains, although the trend toward reduced cravings was not statistically significant, suggesting a need for further research in this area. The findings suggest that physical exercise can positively contribute to the treatment of SUD patients by enhancing mental health and QoL.

Pinus mugo Turra and its Therapeutic Potential: A Narrative Review

Pinus mugo Turra is a coniferous species of shrub or small tree typical of central and south-eastern Europe. It is commonly called mugo pine, mountain pine, or dwarf mountain pine referring to its habit and small size. Indeed, this plant lives at higher altitude above 1400 m above the see level where it deals with harsh conditions typical of high mountain. From an ethnotraditional point of view, P. mugo is mainly used for respiratory disorders and wound healing. In particular, its essential oils have been shown to possess interesting antimicrobial and antioxidant activities, which can substantiate its potential therapeutic effect in pulmonary and urinary tract diseases, as well as antinflammatory and antitumor effects. This review also offers a summary on the chemical constituents of P. mugo that contribute to its therapeutic potential.

Network pharmacology prediction to discover the potential pharmacological action mechanism of Rhizoma Dioscoreae for liver regeneration.

Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and in vivo experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.

Therapeutic Efficacy of IL7/CCL19-Expressing CAR-T Cells in Intractable Solid Tumor Models of Glioblastoma and Pancreatic Cancer.

Despite the clinical development of CAR T-cell therapy, its efficacy in solid cancers has yet to be established. This study explored the therapeutic potential and immunologic mechanisms of IL7/CCL19-producing CAR-T therapy in preclinical solid cancer models of glioblastoma and pancreatic cancer. We found that IL7/CCL19-producing CAR-T cells generated from the patient's PBMC showed potent therapeutic effects against the solid cancer model established by inoculating organoids from the autologous tumor tissue.

Potential therapeutic effects of topical recombinant human erythropoietin on burn wound healing: A preliminary randomized double-blind controlled clinical trial

BackgroundBurn injuries can cause significant mortality and morbidity. This study aimed to evaluate the efficiency of topical recombinant human erythropoietin (rhEPO) on enhancing burn wound healing. MethodsIn this randomized double-blind controlled clinical trial, we enrolled 40 participants aged 18 years and older who were referred to a burn center during the first 24 h of burning. The participants with no concurrent comorbidities had superficial and deep second-degree burns, no respiratory burns, no face and perineum burns, no keloid formation, or a healed, fully epithelialized, hypertrophic burn scar. Topical rhEPO or nitrofurazone/Vitamin A was administered every other day, and the patients were scheduled for follow-up visits to receive wound cleansing, debridement, and dressing changes. Burn wound healing response to treatment was measured as the study main outcome. ResultsAt the second follow-up visit, all parameters were significantly lower in the rhEPO group compared with the control group except for itchiness. The results of the next two follow-up sessions were also the same. The total value of the modified Vancouver Scar Scale (VSS) at days 5, 7, and 14 was significantly lower in the rhEPO group compared with the routine of care group.Trial Registry Date: 2022–03-02, Trial Registry number: IRCT20190810044500N23 ConclusionsThe results of the present study suggested that topical rhEPO is a potential option in burn wounds and patient satisfaction, without causing intolerable side effects.

High β-sitosterol-D-glucoside content in sweet potato varieties and its anti-breast cancer potential through multiple metastasis-associated signals

β-Sitosterol-D-glucoside (β-SDG) is a phytosterol compound whose antitumor activity has been confirmed by previous studies. However, its suppression on breast cancer remains unclear. To that purpose, we isolated β-SDG from sweet potato and investigated the breast-cancer-inhibiting mechanism using proteomic analysis. The sweet potato species S6 with high β-SDG content were chosen form 36 species and β-SDG was isolated by HPLC. Afterwards, an in situ animal model of breast cancer was established, and β-SDG significantly reduced the tumor volume of MCF-7 xenograft mice. Proteomic analysis of tumor tissues revealed that 127 of these proteins were upregulated and 80 were downregulated. Gene ontology and network analysis showed that regulatory proteins were mainly associated with epithelial-mesenchymal transition (EMT), myogenesis, cholesterol homeostasis, oxidative phosphorylation and reactive oxygen pathways, while Vimentin, NDUF, VDAC1, PPP2CA and SNX9 were the most significant 5 node degree genes. Meanwhile, in vitro and in vivo results showed that the protein expression of PPP2CA and Vimentin, which are markers of EMT, were involved in breast cancer cell metastasis and could be reversed by β-SDG. This work highlights β-SDG as a bioactive compound in sweet potato and the potential therapeutic effect of β-SDG for the treatment of breast cancer by inhibiting metastasis.

Ischemic-Preconditioning Induced Serum Exosomal miR-133a-3p Improved Post-Myocardial Infarction Repair via Targeting LTBP1 and PPP2CA.

Ischemic preconditioning-induced serum exosomes (IPC-exo) protected rat heart against myocardial ischemia/reperfusion injury. However, whether IPC-exo regulate replacement fibrosis after myocardial infarction (MI) and the underlying mechanisms remain unclear. MicroRNAs (miRs) are important cargos of exosomes and play an essential role in cardioprotection. We aim to investigate whether IPC-exo regulate post-MI replacement fibrosis by transferring cardioprotective miRs and its action mechanism. Exosomes obtained from serum of adult rats in control (Con-exo) and IPC groups were identified and analyzed, subsequently intracardially injected into MI rats following ligation. Their miRs profiles were identified using high-throughput miR sequencing to identify target miRs for bioinformatics analysis. Luciferase reporter assays confirmed target genes of selected miRs. IPC-exo transfected with selected miRs antagomir or NC were intracardially administered to MI rats post-ligation. Cardiac function and degree of replacement fibrosis were detected 4 weeks post-MI. IPC-exo exerted cardioprotective effects against excessive replacement fibrosis. MiR sequencing and RT-qPCR identified miR-133a-3p as most significantly different between IPC-exo and Con-exo. MiR-133a-3p directly targeted latent transforming growth factor beta binding protein 1 (LTBP1) and protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA). KEGG analysis showed that transforming growth factor-β (TGF-β) was one of the most enriched signaling pathways with miR-133a-3p. Comparing to injection of IPC-exo transfected with miR-133a-3p antagomir NC, injecting IPC-exo transfected with miR-133a-3p antagomir abolished protective effects of IPC-exo on declining excessive replacement fibrosis and cardiac function enhancement, while increasing the messenger RNA and protein expression of LTBP1, PPP2CA, and TGF-β1in MI rats. IPC-exo inhibit excessive replacement fibrosis and improve cardiac function post-MI by transferring miR-133a-3p, the mechanism is associated with directly targeting LTBP1 and PPP2CA, and indirectly regulating TGF-β pathway in rats. Our finding provides potential therapeutic effect of IPC-induced exosomal miR-133a-3p for cardiac repair.

Antiviral effect of cannabidiol on K18-hACE2 transgenic mice infected with SARS-CoV-2.

The aim of this study was to determine the antiviral activity of cannabidiol (CBD) against SARS-CoV-2 infection. CBD is the second most studied cannabinoid obtained from Cannabis plants. We investigated the potential use of CBD, which has so far proven to have a positive effect on different diseases, in the SARS-CoV-2 infection. To test this, invivo studies were carried out using K18-hACE2 transgenic mice. To reveal the potential therapeutic effect of the CBD at the histopathological and molecular level challenge experiments were performed. The study was designed with two groups (n = 10) and in the treatment group animals were infected with SARS-CoV-2 virus strain B.1.1.7 alpha before the administration of CBD. While the disease progressed and resulted in death in the control group that was infected by the virus alone, it was observed that the infection slowed down and the survival rate increased in the mice treated with CBD along with the virus. In this study, K18-hACE2 transgenic mice infected with the wild SARS-CoV-2 virus were used to investigate and prove the antiviral activity of CBD.

Potential Therapeutic Effects of Flavonoid-Rich Extract of Carica Papaya Against Inflammation, Pain, and Pyrexia in Experimental Animals

Potential Therapeutic Effects of Flavonoid-Rich Extract of Carica Papaya Against Inflammation, Pain, and Pyrexia in Experimental Animals

Effects of Berberis asiatica, Withania somnifera, and Their Combination on Body Weight in Streptozotocin-Nicotinamide-Induced Type 2 Diabetes in Wistar Rats.

Introduction Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, impaired insulin secretion, and beta cell dysfunction, often leading to chronic hyperglycemia and associated complications. Berberis asiatica (BA) and Withania somnifera (WS) are ancient medicinal plants with a reputation for having potential therapeutic effects in diabetes management. The purpose of this study was to look into how body weight (BW) was affected in streptozotocin-nicotinamide (STZ-NIC) induced T2DM in Wistar rats by BA, WS, and their polyherbal combination (PHC). Materials and methods Seventy-eight Wistar rats of both sexes were divided into 13 groups, with six rats in each group, including normal and diabetic controls, and treated with varying doses of BA, WS, and PHC. The rats were under observation over the course of 35 days for any change in BW. The Organization for Economic Co-operation and Development (OECD) rules and guidelines were followed in the conduct of acute toxicity tests. One-way analysis of variance (ANOVA), followed by Tukey-Kramer post hoc tests, was used for statistical analysis. Results The findings indicated that the highest dose of BA (1000 mg/kg) significantly improved BW in diabetic rats, approaching that of the normal control group. The combination of BA and WS also demonstrated significant improvements in BW, suggesting a synergistic effect. The standard antidiabetic drugs, metformin and glimepiride, were effective in increasing BW in diabetic rats. Conclusion The study concludes that BA, WS, and their combination have a positive impact on BW management in T2DM rats, with the combination therapy showing enhanced effects. These findings support the potential utilization of these herbs in managing BW and other T2DM-associated metabolic disturbances and abnormalities.

Therapeutic vaccine targeting dual immune checkpoints induces potent multifunctional CD8+ T cell anti-tumor immunity

BackgroundVaccines targeting immune checkpoints represent a promising immunotherapeutic approach for solid tumors. However, the therapeutic efficacy of dual targeting immune checkpoints is still unclear in renal carcinoma. MethodsAn adenovirus (Ad) vaccine targeting B7H1 and B7H3 was developed and evaluated for its therapeutic efficacy in subcutaneous, lung metastasis or orthotopic renal carcinoma mouse and humanized models using flow cytometry, Enzyme-linked immunosorbent spot (ELISPOT), cytotoxic T lymphocyte (CTL) killing, cell deletion, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) assays. ResultsThe Ad-B7H1/B7H3 immunization effectively inhibited tumor growth and increased the induction and percentages of CD8+ T cells in subcutaneous tumor models. The vaccine enhanced the induction and maturation of CD11c+ or CD8+CD11c+ cells, promoting tumor-specific CD8+ T cell immune responses. This was evidenced by increased proliferation of CD8+ T cells and enhanced CTL killing activity. Deletion of CD8+ T cells in vivo abolished the anti-tumor effect of the Ad-B7H1/B7H3 vaccine, highlighting the pivotal role of functional CD8+ T cell immune responses. Moreover, significant therapeutic efficacy of the Ad-B7H1/B7H3 vaccine was observed in lung metastasis, orthotopic, and humanized tumor models through multifunctional CD8+ T cell immune responses. ConclusionsThe Ad vaccine targeting dual immune checkpoints B7H1 and B7H3 exerts a potent therapeutic effect for renal carcinoma and holds promise for solid tumor treatment.