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Polyphenol Fraction of Cyclocarya Paliurus Leaves Modulates Intestinal Microbiota and Alleviates Type 2 Diabetes Mellitus in Mice
No full textBackground: Type 2 diabetes mellitus has become a serious social concern, and diet-based therapies, such as those involving the Cyclocarya paliurus leave tea are gaining attention for preventing and alleviating diabetes mellitus. The objective of the present study was to determine the active components of this tea and understand the associated mechanism. Methods: The active fraction of C. paliurus was traced using the Cell Counting Kit-8 in response to streptozotocin-induced cell damage, and its components were identified using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Flow cytometry and western blotting were performed to examine the effects of the active fraction on streptozotocin-induced pancreatic β cell damage. A high-fat diet combined with streptozotocin-induced animal model was used to identify the effects of this extract against type 2 diabetes mellitus following 8 weeks of gavage administration. Results: The polyphenol fraction of C. paliurus protected against streptozotocin-induced cell damage and up-regulated cleaved caspase-3 and the Bax/Bcl-2 ratio in pancreatic β cells (p < 0.05). Moreover, this administration of the extract effectively reduced body weight, blood glucose level, and increased insulin sensitivity (p < 0.05). The treatment also alerted the abundance of gut microbiota, particularly by upregulating the abundance of Akkermansia and decreasing pathogenic bacteria genus Helicobacter (p < 0.05). Conclusions: Our findings suggested that the polyphenol fraction of C. paliurus could be a potential candidate for gut microbiota modulation as a dietary component for the prevention or management of type 2 diabetes mellitus
The Role and Importance of Fiber Consumption in Chronic Non-Communicable Diseases: Introducing a Fiber Pyramid as a Tool to Increase Its Consumption in Mexican Adults
Get PDFBackground: Chronic non-communicable diseases are a growing public health concern worldwide, presenting a significant global challenge to address. Mexico has a high level of prevalence of chronic non-communicable diseases. Studies indicate that dietary fiber (DF) in foods such as vegetables, whole grains, fruits, and legumes protects against chronic non-communicable diseases. This review centers on finding scientific evidence regarding the DF properties and functional characteristics in chronic non-communicable diseases and the importance of its consumption in chronic non-communicable disease management and prevention in Mexico. Methods: We conducted a comprehensive search for relevant articles on the effect of DF on chronic non-communicable diseases. Our search spanned multiple reputable databases, including PubMed, Scopus, Google Scholar, and Web of Science, ensuring a thorough and reliable review of the existing literature. Results: Studies and clinical trials with isolated and extracted fibers from different sources have shown alterations in the composition and activity of the intestinal microbiota, which have important implications for the development and control of chronic non-communicable diseases. Thus, promoting DF within dietary guidelines could be an option to improve public health. Conclusions: This article not only presents scientific evidence but also offers a practical tool for healthcare professionals. By promoting DF and educating the public to meet the recommended intake of ≥25 g/day, we can potentially prevent the development and enhance the control of chronic non-communicable diseases among Mexican adults
Effect of Inhibition of Galectin-3 Expression on Lipid Accumulation and Atherosclerosis Lesions in a Rat Model of Carotid Atherosclerosis
No full textObjective: Galectin-3 (Gal-3), is a crucial protein involved in regulating cell adhesion, inflammation, and fibrosis, thereby playing a pivotal role in the occurrence and progression of Atherosclerosis (AS). Using the rat carotid artery AS model, this study aimed to investigate the regulatory effects of Galectin-3 expression on lipid accumulation and AS lesion. Methods: Thirty male Wistar rats, aged 10 weeks, were randomly assigned to three groups: the control, model, and treatment groups, each comprising 10 rats. In the control group, dissection was limited to the left common carotid artery. Moreover, the carotid atherosclerosis model was induced in both the model and treatment groups. The treatment group was administered with 10% Modified citrus pectin (MCP) concurrently one week before surgery. Blood and tissue samples were collected on the day after the operation, and the atherosclerosis modeling was observed using Hematoxylin-Eosin (H&E) staining. The levels of triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein were assessed in these three rat groups. Oil red O staining was used to analyze the lipid deposition in the intima of arteries. Furthermore, the expression levels of Cholesterol ester hydrolase (CEH) and Gal-3 in the carotid artery were determined by quantitative Real-time Polymerase Chain Reaction (qRT-PCR) and Western blot analysis. Enzyme-Linked immunosorbent assay (ELISA) was employed to assess the expression levels of Gal-3, tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), Interleukin 6 (IL-6), and Interleukin 8 (IL-8). Additionally, flow cytometry was utilized to evaluate mitochondrial membrane potential (MMP) and the expression of iron death-related proteins (Glutathione Peroxidase 4 and Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase 4 (NOX4)) was determined using Western blot analysis. Results: Gal-3 was highly expressed in atherosclerotic rats. After the inhibition of Gal-3, a significant reduction was observed in the levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol in tissues. The degree of lesions, the levels of inflammatory factors and iron death were significantly alleviated, while the expression of CEH was increased. Conclusion: Inhibition of Galectin-3 can slow down the lesion and lipid accumulation in carotid atherosclerotic rats
Molecular Docking, Synthesis, and QSAR Study of Phthalazine and Their Substituted Copper (II) and Zinc (II) Derivatives as Anti-Rheumatic Agents
No full textBackground: Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation, pain, stiffness, and swelling in the affected joints typically with a symmetrical pattern on both sides of the body, which becomes more drastic and can also affect other organs and systems in the body. Thus, regular monitoring, follow-up of the disease, and exploring new metal-based therapy with minimum or no side effects are important challenges for managing the disease effectively. Methods: Complexes with the common formula [M(L)(OAc)] (M = Cu (II) or Zn (II)) and HL = 2-(-3-hydroxy-2-naphthoyl)-3,4,4a,5,10,10a-hexahydro-1H-5,10-benzeno-benzo [g] phthalazine-1,4-dione) were synthesized through a reaction between phthalazinedione derivative (HL) and Cu (II) and Zn (II) acetates. For synthesis and description of the HL, various elemental analyses, UV-Vis, infera red (IR), 1H-NMR, 13C-NMR, conductance, thermal gravimetric analysis (TGA), and magnetic moments were accurately performed. Additionally, the analgesic and anti-inflammatory activities of phthaline metal compounds were identified using adjuvant arthritis model comprising of forty-eight Sprague-Dawley rats (200–250 g). In that model, the rats were categorized into two main groups: control group (received sodium carboxymethyl cellulose (SCMC) solvent, n = 6) and arthertis group (n = 42). In arthertic group, the rats had been inoculated by the reagent of collagen-adjuvant arthritis into the left paw pad. After 45 days, the arthertic rats were further divided into seven different groups (n = 6 each): arthritic control, piroxicam-treated, zinc acetate-treated, copper acetate-treated, HL, copper complex-, and zinc complex-treated groups. Then for all treated and non-treated rats, paw edema, pain and pressure tolerance measurements, and mobilization tolerance (pain scoring) were identified as measures of improvement in the disease activity following the respective piroxicam as standard and metal compounds. Results: Phthalazine Copper (II) and Zinc (II) complexes showed anti-inflammatory action against rheumatoid arthritis as predicted by an equation with a regression correlation (R2 = 0.95) calculated using quantitative structure activity relationship (QSAR) analysis. The anti-inflammatory activity of synthesized phthalazine metal complexes was supported by the application of docking analysis and in vivo model of collagen adjuvant arthritis in rats, respectively. The results of docking showed that phthalate-zinedine derivatives in keto form structure have a MolDock Score of –130.726 Kcal/mol and a MolDock Rerank Score of –96.2 Kcal/mol, respectively. These suggest that phthalazinedione derivatives in keto form are strong and anchored with a cyclooxygenase-2 active site, which consequently decreases the inflammatory pathways associated with the progression of rheumatoid arthritis (RH). RH rats treated with piroxicam reported significant (p = 0.001) anti-inflammatory activity with an improved bor RI and analgic effects measured by both increase in pain tolerance and decrease in pain score compared to RH- non-treated rats. In addition to that, significant (p = 0.01) analgesic and anti-inflammatory effects of the ligand (HL) and its copper and zinc complexes than piroxicam RH treated rats and non-treated RH rats, respectively, were reported when the complexes were applied to in vivo rat models with collagen adjuvant arthritis. Conclusions: Phthalazinedione derivative (HL), Cu (II), and Zn (II) acetates combined to treat rheumatoid arthritis (RH) show a good docking with inflammatory enzyme cyclooxygenase-2 (COX-2), with improved anti-inflammatory activities against RH as measured by docking and in vivo rat model of collagen adjuvant arthritis. In addition, the newly synthesized phthalazine metal complexes disclosed a significant anti-inflammatory and analgesic effect sequenced as [Zn(L)(OAc)] > HL > [Cu(L)(OAc)]
Role of Opioid Growth Factor-Opioid Growth Factor Receptor (OGF-OGFr) Axis in Cancer Management
No full textOpioid growth factor (OGF) and its receptor, opioid growth factor receptor (OGFr), create a physiological axis that affects cellular growth by decreasing the G1/S phase of cell division in both normal and malignant cells. The OGF-OGFr axis is potent, rapid, reversible, stereospecific, receptor-mediated, serum- and anchorage-independent, dosage- and duration-dependent, and tonically active and is present at physiological doses. Cancer progression can be suppressed or accelerated when the OGF-OGFr pathway is altered by adding OGF externally or obstructing its receptor. Exogenous or endogenous antagonists of OGF and OGFr have been shown to modulate cancer cell propagation. OGF-OGFr pathway activation has the potential to reduce tumor development and metastasis and enhance the effectiveness of chemotherapy and radiation therapy while preserving healthy tissues, as shown by preclinical research conducted in animal models. Clinical trials in humans have also demonstrated promising results in treating various types of cancer, encompassing pancreatic, lung, and ovarian cancers. This review aims to summarize the recent developments that show the importance of the OGF-OGFr axis in cancer treatment
The Establishment of Human Embryonic Stem Cell Lines Demonstrated that Mosaic Embryos Have the Potential of Self-Correction
No full textBackground: Low-level mosaicism is a common trait of early human development. Although mosaic embryos may lead to healthy live births, the direct effects of mosaicism are unknown. While embryo self-correction was demonstrated in mouse models, humans can only study the effects of chromosomal aberrations and blastocyst mosaicism on the early peri-implantation period by extending in vitro embryo culture up to 12 days post-fertilization. Methods: The established culture protocols were followed to generate embryonic stem cells. The 24 high-quality mosaicism/aneuploid mosaicism blastocysts were detected by preimplantation genetic testing for aneuploidy (PGT-A). The isolated inner cell masses (ICMs) were seeded onto feeder-free dishes, and after 10–12 days of culture, there were six blastocyst ICM-generated stem cell clones. The cells shed during the stem cell growth were harvested, and next-generation sequencing was performed on stem cells and the shed cells. To test pluripotency, a small number of stem cells were isolated and subcultured. Results: The PGT-A status was confirmed from the results of next-generation sequencing of stem cell exfoliated cells and stem cells. The mosaics in five blastocysts were fully repaired while the mosaic in one blastocyst was partially repaired. Simultaneously, the cells were verified to have pluripotency and the ability to differentiate into three germ layers by immunofluorescence, flow cytometry, and in vitro differentiation analyses. Conclusion: Human mosaicism/aneuploid mosaicism blastocysts have the potential for self-correction by eliminating mosaic cells
Phytochemical Profiling and Synthesis of Fernandoa Adenophylla Syrup and its Evaluation in Multiple Biological Activities
No full textBackground: The adverse effects of synthetic drugs have led to a rising interest in natural alternatives globally. In Pakistan, rural areas heavily rely on plant-based treatments for 80% of healthcare needs. Fernandoa adenophylla (F. adenophylla), a woody plant native to South Asia, possesses antimicrobial properties and has been traditionally used for various ailments. This research aims to formulate a syrup from F. adenophylla hydromethanolic leaf extracts, leveraging its antioxidant properties. The study follows United States Pharmacopeia guidelines to assess the potential anti-emetic properties of the syrup as an alternative to synthetic drugs, with a specific focus on emesis in female Albino Mice. Methods: By the United States Pharmacopeia (USP) guidelines, we meticulously prepared a simple syrup and a decoction. The syrup was formulated by blending the decoction and simple syrup in a 1:5 ratio supplemented with 0.2% Methyl Paraben and rose oil. Antibacterial activity was assessed using urine samples, and antibiotic susceptibility was determined with ten antibiotics. The syrups antibacterial and antifungal properties were evaluated through well diffusion assays. The insecticidal activity was tested on Tenebrio molitor and Dermetes ladies insects. Antioxidant activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, and antiemetic effects were investigated in Albino female mice with castor oil-induced emesis. Statistical analysis was performed using statistical package for social sciences (SPSS) (p < 0.05). Results: Our findings revealed noteworthy antibacterial activity, with the highest inhibition observed against V. cholera (32 mm). Additionally, the syrup demonstrated substantial antifungal activity, particularly against Rhizopus spp. (21 mm). Impressively, the syrup exhibited robust insecticidal properties, causing mortality rates of 80% in Tenebrio molitor and 70% in Dermetes ladarius. Conclusion: The investigation of F. adenophylla leaf extract revealed the presence of potential antimicrobial compounds, which hold promise for treating various microbial infections. Phytochemical screening unveiled the presence of essential bioactive constituents such as terpenoids, flavonoids, saponins, glycosides, tannins, and reducing sugars in the F. adenophylla leaf extract. Moreover, the study suggests that the plant-based syrup derived from F. adenophylla may possess valuable antioxidant properties, making it a candidate for exploration in the realm of therapies targeting oxidative stress-related health conditions
Binimetinib Attenuates Skin Fibrosis by Inhibiting the TGF‐β1 Signaling Pathway
No full textBackground: Dermatofibrosis diseases (e.g., keloids) are abnormal pathological results of the tissue healing process. They are characterized by the excessive proliferation of fibroblasts in the dermis and the excessive deposition of extracellular matrix. Existing treatments for dermatofibrosis have not achieved satisfactory results. The therapeutic efficacy of Binimetinib as a clinical agent for treating cutaneous malignancies in the field of fibrosis has not been extensively studied. Therefore, this study aims to investigate the antifibrotic activity of Binimetinib both in vitro and in vivo against dermal fibrosis, as well as elucidate its underlying mechanism. Methods: In this study, we explored the potential effects and underlying mechanisms of Binimetinib on dermal fibrosis both in vitro and in vivo. In the in vitro experiments, we applied the Cell Counting Kit-8 (CCK-8) assay, wound healing assay, and western blotting to examine the inhibitory effects of Binimetinib on the proliferation, migration, and activation of mouse primary dermal fibroblasts (PSFs) and human keloid fibroblasts (KFs). In the in vivo experiments, we established a bleomycin mouse dermal fibrosis model and a nude mouse subcutaneous keloid model to verify the inhibitory effect of Binimetinib on dermal thickening in bleomycin model mice and on growth in subcutaneous keloid model in nude mice. Additionally, we investigated the expressions of proteins related to the transforming growth factor-β1 (TGF-β1) signaling pathway. Results: In vitro experiments showed that Binimetinib effectively suppressed the proliferation, migration, and activation of KFs and PSFs in a dose-dependent manner (p < 0.05). In vivo experiments revealed that Binimetinib attenuated dermal thickening induced by bleomycin (BLM), reduced hydroxyproline content, and reduced the expression of fibrosis markers in a bleomycin-induced dermal fibrosis model (p < 0.05). Moreover, in a nude mouse subcutaneous keloid model, Binimetinib not only inhibited keloid proliferation and weight gain but also suppressed the expression of fibrosis markers (p < 0.05). Further mechanistic studies indicated that Binimetinib inhibited both TGF-β1/recombinant SMAD family member (Smad) signaling and TGF-β1/non-Smad signaling pathways associated with fibrosis (p < 0.05). Conclusions: In summary, our results confirm that Binimetinib effectively suppresses fibrosis both in vivo and in vitro by inhibiting the TGF pathway, demonstrating significant potential for fibrosis treatment
A Study on the Role of Bifidobacterium Bifidum in Antagonizing Brain Tissue Injury and Inflammation in a Febrile Convulsion Model in Mice
Get PDFBackground: Febrile convulsions in children are often triggered by high fever and can lead to acute neurological episodes with potential long-term consequences on cognitive function. Probiotics, particularly bifidobacteria, have demonstrated promising potential in modulating immune function and intestinal health. However, their role in neurological disorders, including febrile convulsions, is yet to be fully explored. Therefore, this study aimed to investigate the therapeutic impacts of Bifidobacterium bifidum on mitigating brain tissue damage and inflammation utilizing a mouse model experiencing febrile convulsions. Methods: To assess the impact of Bifidobacterium bifidum on febrile convulsions, a mouse model was established by administering dry yeast suspension and pentylenetetrazol solution. Using this model, we examined the changes in anal temperature, convulsion onset time, and convulsion duration. Histological analysis through Hematoxylin and Eosin (H&E) staining was employed to study the neuronal morphology in the mouse hippocampus. Furthermore, the levels of serum Cyclic Adenosine Monophosphate (cAMP) and Prostaglandin E2 (PGE2) were assessed using Enzyme-Linked Immunosorbent Assay (ELISA). Additionally, protein expressions of cyclooxygenase-2 (COX-2), Inducible Nitric Oxide Synthase (iNOS), Gamma-Aminobutyric Acid Type A Receptor (GABAAR), and glial fibrillary acidic protein (GFAP) were determined through western blot analysis, while mRNA expressions of inflammatory markers Interleukin 1 beta (IL-1β), Interleukin 6 (IL-6), and Tumor Necrosis Factor alpha (TNF-α) in hippocampal tissue were determined by quantitative Polymerase Chain Reaction (qPCR). Results: In comparison to the model group, mice in the Bifidobacterium group exhibited a significant reduction in anal temperature (p < 0.05), an increase in the time to onset of convulsions (p < 0.05), a shorter duration of convulsive episodes (p < 0.05), and an enhanced expression of GABAAR protein (p < 0.05). Additionally, the Bifidobacterium group showed lowered serum levels of cAMP and PGE2 (p < 0.05), improved neuronal cell morphology in the hippocampus, and a decrease in the expression of COX-2, iNOS, and GFAP proteins in the brain tissue (p < 0.05). Furthermore, there was a substantial reduction in the hippocampal tissue levels of pro-inflammatory factors IL-1β, IL-6, and TNF-α mRNA (p < 0.05). Conclusion: Bifidobacterium bifidum exhibits an effective antipyretic and anti-convulsant activity. Its mechanism may be attributed to its ability to reduce fever and inflammation in the brain
Ginkgolic Acid Enhances the Sensitivity of Liver Cancer Cells to Sorafenib via Up-Regulating CFL2
No full textBackground: Ginkgolic acid (GA) impedes the invasion of cancer cells, and reverses the drug resistance of carboplatin-resistant cell lines. This study was conducted to explore the influence of GA on the sensitivity of liver cancer cells to sorafenib (SOR) and the relevant mechanism. Methods: Genes aberrantly expressed in GA-treated liver cancer cells and SOR-resistant liver cancer cells were analyzed by GEO2R, and cofilin 2 (CFL2) level in liver cancer cells was analyzed using the StarBase. Liver cancer cells were transfected with small interfering RNA targeting CFL2 (siCFL2). Subsequently, the cells were subjected to treatments with GA and SOR alone or together. Assessment of the viability, proliferation, and apoptosis of the treated cells was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5‐ethynyl‐2′‐deoxyuridine (EdU) fluorescent staining, and flow cytometry assays, respectively. Quantification of proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (Bcl-2), BCL2 associated X protein (Bax), Cleaved-caspase 3, and CFL2 in cell samples was achieved through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Results: GA diminished cell viability and enhanced the effect of SOR on repressing the viability and proliferation, accelerating apoptosis, decreasing PCNA and Bcl-2 levels, and increasing Bax and Cleaved-caspase 3 levels in liver cancer cells. Low expression of CFL2 was observed in liver cancer cells, however, SOR elevated its level, and GA further enhanced this increment. Silencing CFL2 offset the aforementioned roles of GA in SOR-treated liver cancer cells. Conclusions: GA has the potential to enhance the sensitivity of liver cancer cells to SOR by increasing CFL2 level