Cell Biochemistry and Biophysics最新文献

Cervical high-grade squamous intraepithelial lesions (HSIL) are one of the common types of cervical cancer precancerous changes, and HPV16/18 positivity is a risk factor for HSIL recurrence. By detecting the expression of relevant markers in the lesion tissue of recurrent patients, it is helpful for the diagnosis of HPV16/18 positivity and can provide a basis for disease recurrence risk assessment. Therefore, this study analyzed the relationship between p16, C-myc, PIK3CA proteins and HPV16/18 positivity in recurrent cervical HSIL patients. By examining the p16, C-myc, and PIK3CA proteins in the cervical lesion tissue of 180 HSIL recurrent patients who underwent examination in the hospital from January 2020 to December 2022, this study analyzed the relationship between p16, C-myc, and PIK3CA proteins and HPV16/18 positivity. PIK3CA expression detection found that the proportion of positive expression of p16, C-myc, and PIK3CA in HPV16/18 (+) patients was significantly higher than that in HPV16/18 (-), and the expression of HPV16/18 in HSIL patients was significantly positively correlated with p16, C-myc, and PIK3CA. Meanwhile, a prediction model F was constructed based on binary logistic regression analysis data with good fit, and through ROC curve analysis. It was found that p16, C-myc, PIK3CA, and logistic model F can effectively predict HPV16/18 (+), with model F having the best diagnostic performance.

Type 2 diabetes (T2D), also known as non-insulin-dependent diabetes mellitus, represents the prevailing manifestation of diabetes, encompassing a substantial majority of cases, ~90-95%. Plant-derived antidiabetic leads are being intensively explored due to their safety and effectiveness. The main objective of the present study is to evaluate the anti-diabetic potential of the traditional formulation Karisalai Karpam through in-vitro and in-silico investigations. The in-vitro and in-silico investigation of traditional polyherbal preparation Karisalai Karpam (KK) chooranam were performed to ascertain its inhibitory potential against α-amylase and α-glucosidase enzymes along with antioxidant (DPPH and ABTS) and phytochemical analysis. The results of enzyme inhibitory activity of KK witnessed highest activity against α-glucosidase enzyme with a percentage inhibition of 84.66 ± 2.50% (IC₅₀,187.9 ± 5.79 μg/ml) followed by moderate level of α-amylase inhibition exhibited with 72.94 ± 3.66% (IC₅₀, 241.6 ± 9.76 μg/ml). Additionally, the strongest antioxidant activity was observed in quenching DPPH^• (IC₅₀,154.8 ± 14.53 μg/ml) and ABTS^+• radicals (IC₅₀,148.6 ± 29.74 μg/ml). The outcome of the molecular docking studies indicated that among the 17 compounds analysed, the lead such as acalyphin, apigenin, humulene, and indirubin exhibited a prominent binding affinity over the residual binding site of α-glucosidase. It's important to note that the catalytic site of the enzyme α-amylase is primarily occupied by amyrin, apigenin, arjunolic acid, β-sitosterol, geraniol, and tricetin. In conclusion, the formulation KK demonstrates robust alpha-glucosidase and alpha-amylase inhibitory activity. It's also worth noting that the formulation exhibits noteworthy antioxidant properties, which could provide additional health benefits. The binding mode and energies of the identified phytochemicals against the target enzymes further support the formulation's antidiabetic potential.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a range of conditions that start with the accumulation of fat in the liver (hepatic steatosis) and can progress to more severe stages like steatohepatitis (NASH) and fibrosis without drinking alcohol. Environmental and genetic variables both contribute to MAFLD's development, with various biological processes and mediators involved at every phase. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that are not translated into protein and are over 200 nucleotides long. They can impact genes that encode protein by controlling transcriptional and post-transcriptional procedures. Dysregulation of lncRNA has been connected to several liver diseases, including MAFLD. Recent research has linked lncRNAs to MAFLD pathology in both patients and animal models. However, the roles of most lncRNAs in MAFLD pathology are still not well recognized. This review provides a comprehensive catalog of recently reported lncRNAs in the pathogenesis of MAFLD and summarizes the current knowledge of lncRNAs usage as therapeutic strategies in MAFLD, the most common liver disease. Collectively, lncRNA's targeting could potentially offer a therapeutic approach by modulating MAFLD.

This study investigates the therapeutic effects of D-Xylose, a natural sugar, on non-alcoholic fatty liver disease (NAFLD), focusing on the expression of the lysozyme gene (LYZ) in macrophages. Using the single-cell dataset GSE136103 for NAFLD, researchers analyzed macrophage populations and other groups utilizing the Seurat package in R, while a differential analysis was performed on the NAFLD dataset GSE61260 using the limma package. Both in vitro and in vivo models, including cell culture, mouse models, RT-qPCR, Western blot, ELISA, and histopathological analyses, were employed to examine the effect of D-Xylose on lipid accumulation, LYZ expression, blood lipid levels, and inflammatory responses. The study found a significant upregulation of LYZ in free fatty acid (FFA)-treated cells and mouse liver tissues, with a subsequent reduction after D-Xylose intervention. Treatment with D-Xylose and Amlodipine led to a notable decrease in lipid accumulation, as evidenced by reduced triglyceride and cholesterol levels. D-Xylose demonstrated a greater improvement in lipid metabolism than Amlodipine. Additionally, D-Xylose significantly mitigated inflammatory responses, reducing levels of inflammatory markers such as IL1R, IL6, MYS8, TNF, NF-κB, and IL-1. Furthermore, D-Xylose administration significantly reduced liver weight and liver index, with a positive impact on serum liver function and blood lipid levels. The findings suggest that D-Xylose could be a therapeutic intervention for NAFLD by targeting LYZ expression in macrophages, thereby modulating lipid metabolism and inflammatory responses.

Type 2 diabetes mellitus (T2DM) is usually depicted by relative insulin deficiency, raised blood glucose levels, and the predominant risk factor, insulin resistance. Hence, the development of insulin sensitizer drugs targeting PPAR-γ receptors has expanded enormous interest as an attractive choice for T2DM treatment. Thiazolidinediones (TZD) enhance insulin sensitivity either by directly functioning on gene transcription of the PPARγ receptor related to glucose homeostasis or by systemic sensitization of insulin and, therefore, improved hyperglycemia in a wide range of patients. However, severe complications and adverse effects of TZDs necessitate the development of an efficacious and reliable insulin sensitizer from alternative resources. On the contrary, Nature is a rich source of anticipated effective and safer medicine; more than fifty percent of drugs on the market are developed from natural products. Hence, searching for a new PPAR-γ agonist from bioactive secondary compounds of medicinal plants along with greater efficacy and safety is a recognized and consistent tactic for developing novel antidiabetic agents. Pulicaria jaubertii is a fragrant perennial aromatic plant with anti-inflammatory, antidiabetic, antimicrobial, antimalarial, and insecticidal properties. The current study was designed to use a computer-aided drug design to explore the best antidiabetic compounds from P. jaubertii. Herein, the molecular docking study of 80 investigated ligands against the PPAR-γ receptor identifies the highest docking score for five ligands ranging from -8.9 kcal/mol to 8.0 kcal/mol, which is also more significant than the standard drug pioglitazone (-7.7 kcal/mol) determined by the PyRx 8.0 virtual screening software. GLN286, CYS285, SER289, TYR473, MET364, ARG288, ILE341, and LEU333 residues are found to be significant contributors to the non-bonded interaction between ligands and receptors. Molecular electrostatic potential (MEP), DFT, molecular orbital (MO), ADMET, and toxicological analyses were performed on the selected five high-scored ligands of P. jaubertii. Results documented that all investigated ligands, especially L4, show considerably excellent profiles in molecular docking, MEP, DFT, MO, ADMET, and toxicological predictions, suggesting our drug-designing approaches may contribute to the development of a novel antidiabetic drug for the treatment of T2DM from natural resources.

Inflammatory and autoimmune diseases are pathological immune disorders and pose significant public health challenges due to their impact on individuals and society. Cytokine dysregulation plays a critical role in the development of these disorders. Interleukin (IL)-24, a member of the IL-10 cytokine family, can be secreted by various cell types, including immune and non-immune cells. The downstream effects of IL-24 upon binding to its receptors can occur in dependence on, or independently of, the Janus kinase (JAK)/signal transducer and the activator of transcription (STAT) signaling pathway. IL-24 and its downstream pathways influence crucial processes such as cell differentiation, proliferation, apoptosis, and inflammation, with its role varying across different diseases. On the one hand, IL-24 can inhibit the activation of pathogenic cells and autoimmune responses in autoimmune ocular diseases; on the other hand, IL-24 has been also implicated in promoting tissue damage by fostering immune cell activation and infiltration in psoriasis and allergic diseases. It suggests that IL-24, as a multifunctional cytokine, has complex regulatory functions in immune cells and related diseases. In this paper, we summarize the current knowledge on IL-24's immunomodulatory actions and its involvement in inflammatory and autoimmune disorders. Such insights may pave the way for novel therapeutic strategies for these diseases.

Mathematical neuroscience investigates how calcium distribution in nerve cells affects the neurological system. The interaction of numerous systems is necessary for the operation of several cellular processes in neuron cells, such as calcium, buffer, ER etc. The dynamics of interacting parameters give useful information on neural cell function. This work uses a mathematical model to analyze the dynamic interactions of buffer and ER inside neurons, considering their spatial properties. While buffers bind to calcium ions and lower their concentration, the endoplasmic reticulum (ER) serves as a reservoir, holding a significant number of free calcium ions. The uncertainty of initial values of calcium concentration poses challenges for researchers to develop calcium signaling models. In this article, we examined the exact solution and approximate solution of the mathematical model that was analyzed using the fuzzy undetermined coefficient approach. MATLAB is being used to perform the simulation. Endoplasmic reticulum and buffer have been found to have a substantial impact on calcium signaling. Fuzzy differential equation Provides a useful tool for evaluating complicated processes with imprecise values when ordinary differential equations perform not precisely. They allow for the examination of dynamic processes under fuzzy settings, which contributes to advances research.

Schistosomiasis, a parasitic disease caused by Schistosoma species such as S. haematobium, S. mansoni, and S. japonicum, poses a significant global health burden. The thioredoxin glutathione reductase (TGR) enzyme, crucial for maintaining the parasite's redox balance and preventing oxidative stress, has been identified as a promising target for anti-schistosomal drug development. This study aims to identify potential TGR inhibitors from Azadirachta indica phytochemicals using molecular modeling approaches. We screened 60 compounds derived from A. indica bark and leaves through molecular docking to assess their binding affinity, followed by the evaluation of binding-free energies for the most promising candidates. Drug-likeness and pharmacokinetic properties were assessed, and molecular dynamics simulations were conducted to explore the conformational stability of the protein-ligand complexes. Our findings revealed that several A. indica compounds exhibited significantly lower docking scores (up to -9.669 kcal/mol) compared to the standard drug praziquantel (-4.349 kcal/mol). Notably, Isorhamnetin, Isomargolonone, Nimbaflavone, Quercetin, and Nimbionol demonstrated strong interactions with TGR, although Isorhamnetin showed potential mutagenicity. Further binding free energy calculations and molecular dynamics simulations confirmed the stability of Isomargolonone, Nimbionol, and Quercetin as potential TGR inhibitors. In conclusion, these findings suggest that Isomargolonone, Nimbionol, and Quercetin warrant further experimental validation as promising candidates for anti-schistosomal therapy.

This study aims to elucidate the role of miR-378a-3p in facilitating the proliferation and differentiation of synovium-derived mesenchymal stem cells (SMSCs) into chondrocytes. The effects of overexpressing miR-378a-3p on SMSCs were investigated through histological analysis, quantitative PCR, and western blotting. Then we identified binding sites of miR-378a-3p with BMP2 through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses and predictions from the RegRNA 2.0 database. Subsequently, BMP2 was confirmed as the target by which miR-378a-3p promotes the chondrogenic differentiation of SMSCs using a luciferase reporter gene assay and an miR-378a-3p RNA interference plasmid. Finally, by constructing a rat model with articular cartilage damage, we detected the reparative effects of miR-378a-3p overexpression on cartilage damage. Additionally, we verified the mechanism by which miR-378a-3p promotes chondrogenic differentiation in SMSCs. MiR-378a-3p enhances the proliferation and differentiation of SMSCs into chondrocytes by modulating the BMP2-Smad signaling pathway, thereby facilitating repair processes for articular cartilage injuries in rats. Notably, knockdown of BMP2 diminished the reparative efficacy of miR-378a-3p on articular cartilage damage. Upregulation of miR-378a-3p promotes chondrogenic differentiation in SMSCs through activation of the BMP2-Smad pathway, positioning it as a potential therapeutic target for osteoarthritis.

Adaptogens, comprising plants and mushrooms, modulate the immune system, energy balance, and various physiological processes, including reproduction. Despite their potential benefits, the impact of adaptogens on reproductive function remains understudied. This review examines the effects of common adaptogens on male and female reproductive functions, highlighting their regulation of neuro-endocrine-immune interactions crucial for reproduction. While existing literature reveals varying impacts on reproductive function, most adaptogens exhibit beneficial effects, modulating neuroimmunology and promoting gonadal steroidogenesis, spermatogenesis, and folliculogenesis through direct mechanisms or suppression of oxidative stress and inflammation. Further experimental research is necessary to elucidate the mechanisms of action of adaptogens, which would significantly advance the management of reproductive disorders and other diseases. Validating these findings in clinical trials is also essential.