International journal of biochemistry and molecular biology最新文献

Objective: Lately, various scientists have been paying a lot of consideration to the design of operational antimicrobial agents due to the rise of multiple drug-resistant strains. Therefore, this work is aimed at discovering the biochemical behavior of the analyzed polypeptides in relation to glutamine amidotransferase GatD (pdb id: 5n9m) for gram positive bacteria and beta-lactamase class A (pdb id: 5fqq) for gram negative bacteria. Additionally, this study aims to identify the specific atoms involved in the observed biochemical interactions between the studied complexes using computational methods.

Methods: In this work, five polypeptides were studied using insilico approach via Spartan 14 software, molecular operating environment, ADMETSar, and Gromacs.

Results: The descriptors obtained revealed the activities of the studied compounds, the molecular interaction between the studied ligands as well as glutamine amidotransferase GatD (pdb id: 5n9m) and beta-lactamase class A (pdb id: 5fqq) which thereby exposed compound 1 and 5 to be the compounds with greatest ability to inhibit the studied targets among other studied compounds.

Conclusion: Our discoveries may open door for the design of collection of proficient polypeptide-based drug-like compounds as potential anti-microbial agents.

The family of fibroblast growth factors (FGFs) consists of 22 members with diverse biological functions in cells, from cellular development to metabolism. The family can be further categorized into three subgroups based on their three modes of action. FGF19, FGF21, and FGF23 are endocrine FGFs that act in a hormone-like/endocrine manner to regulate various metabolic activities. However, all three members of the endocrine family require both FGF receptors (FGFRs) and klotho co-receptors to elicit their functions. α-klotho and β-klotho act as scaffolds to bring endocrine FGFs closer to their receptors (FGFRs) to form active complexes. Numerous novel studies about metabolic FGFs' structures, mechanisms, and physiological insights have been published to further understand the complex molecular interactions and physiological activities of endocrine FGFs. Herein, we aim to review the structures, physiological functions, binding mechanisms to cognate receptors, and novel biomedical applications of endocrine FGFs in recent years.

In this paper, we explore marine bioactive peptides with anticancer potential sourced from various marine organisms, including tunicates, sea sponges, and mollusks. Peptides like Stylisin and Papuamides have been isolated, identified, and modified to enhance their activity, with many advancing to clinical trials due to their diverse biological activities, promising prospects in medicine. Enzymatic hydrolysis is a favored method for extracting peptides from marine proteins, particularly from sponges known for their rich bioactive compounds. Compounds such as Jaspamide and Homophymins exhibit potent cytotoxic activity against cancer cells, underscoring their therapeutic potential. Additionally, peptides from ascidians and mollusks, such as Aplidine and Kahalalide F, demonstrate significant anticancer properties. This study also explores peptides influencing apoptosis, microtubule dynamics, and angiogenesis, providing insights into potential mechanisms for cancer treatment. While peptides like Neovastat and mycothiazole target known pathways, others such as patellamides act through unknown mechanisms, highlighting the intricate interactions of marine peptides with cancer cells. Overall, marine-derived peptides show promise as valuable candidates for developing novel anticancer therapies.

Marine environments harbor a wealth of bioactive peptides with potential anticancer properties, sourced from diverse organisms like tunicates, sea sponges, and mollusks. Through isolation, identification, and modification, peptides such as Stylisin and Papuamides have shown enhanced activity and progressed to clinical trials, underscoring their therapeutic promise. Enzymatic hydrolysis emerges as a favored method for peptide extraction from marine proteins, with sponges identified as particularly rich sources. Compounds like Jaspamide and Homophymins exhibit potent cytotoxic activity against cancer cells, highlighting their therapeutic potential. Additionally, peptides from ascidians and mollusks, including Aplidine and Kahalalide F, demonstrate significant anticancer properties. The study delves into peptides affecting apoptosis, microtubule dynamics, and angiogenesis inhibition, offering insights into potential cancer treatment mechanisms. Marine-derived peptides hold great promise as valuable candidates for novel anticancer therapies, with ongoing research aimed at unlocking their full therapeutic benefits.

Cadmium (Cd) is a heavy metal pollutant widely distributed in the environment due to industrial activities, mining, and agricultural practices. Cadmium-induced Toxicity exerts profound effects on ER functioning through multiple mechanisms, leading to cellular dysfunction and pathological consequences. Cadmium disrupts protein folding and activates the unfolded protein response (UPR). Cd exposure leads to the accumulation of misfolded proteins, triggering UPR pathways mediated by critical ER transmembrane sensors: IRE1, PERK, and ATF6. The subsequent UPR aims to restore ER homeostasis but can also induce apoptosis under severe stress conditions. Cd disrupts ER calcium homeostasis by inhibiting the SERCA pump, further exacerbating ER stress. The generation of reactive oxygen species (ROS also plays a critical role in Cd toxicity, damaging ER-resident proteins and amplifying UPR activation). Cadmium also affects the lipid metabolism. This review examines the mechanisms by which Cd toxicity impairs ER functioning, disruption of protein folding and quality control mechanisms, and dysregulation of calcium signaling and lipid metabolism. The subsequent cellular consequences, including oxidative stress, apoptosis, and inflammation, are discussed in the context of Cd-induced pathogenesis of diseases such as Cancer and neurodegenerative and cardiovascular disorders. Finally, potential therapeutic strategies must be explored to mitigate the adverse effects of Cd on ER functioning and human health.

Objectives: The current study aimed to correlate OCT1 (organic cation transporter 1) polymorphisms with metformin response variability in Iraqi women with PCOS (polycystic ovarian syndrome) and determine the impact of OCT1 polymorphism. PCOS, an endocrine metabolic disorder, can seriously impact female health including infertility. Although its cause is unclear, it is usually known to be associated with hormonal imbalances. OCT1 is essential for metformin absorption in the liver. Recent research shown that OCT1 polymorphisms affects metformin responsiveness.

Methods: In the present work, a prospective case-control study was conducted at Department of Infertility, Karbala Teaching Hospital for Obstetrics and Gynecology. 100 PCOS patients and 50 healthy controls aged 20-40 were enrolled. Consultant gynecologist diagnosed PCOS patients using Rotterdam criteria and recommended metformin 500 mg twice daily for 3 months. At the start of the trial and after 3 months, all patients and healthy controls underwent hormonal, biochemical and genetic tests.

Results: The similar allelic frequencies of OCT1 polymorphism in PCOS and control groups was observed. Most patients with reference wild type alleles (C) showed considerable hormonal and metabolic responses to metformin, while those with mutant alleles (T) showed non-significant responses.

Conclusion: FSH, prolactin and testosterone hormonal levels may be considered as candidate biomarkers for PCOS detection and metformin related biomedical respond.

Introduction: Human epidemiological studies have shown that diets rich in plant polyphenols have beneficial effects on various diseases including cancer. Epigallocatechin Gallate, a flavonoid polyphenol molecule, has been shown to be both chemotherapeutic and chemo-preventive in the treatment of several forms of cancer, including lung cancer. 80% of cancers of the lungs are non-small cell lung cancers.

Objective: The study was carried out to see the effects of Epigallocatechin Gallate in non-small cell lung cancer cells (A549) using in-vitro studies.

Materials and methods: Cell Viability Assay was performed using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Wound Healing assay was also performed at different concentrations of the compound. Dexamethasone and Doxorubicin, the drugs with anti-cancer properties served as control. A549 cell lines were used.

Results: In the current study, it was demonstrated using Cell viability assay and Wound Healing assay that Epigallocatechin gallate exhibits anti-proliferative activity on A549 lung cancer cells and inhibits cancer cell proliferation in a concentration and time-dependent manner. It was observed that Epigallocatechin gallate (P = 0.0016, P = 0.0018) could significantly inhibit the growth of lung cancer cells with IC50 values 60.55 ± 1.0 μM. The result of wound Healing assay suggests that Epigallocatechin gallate can inhibit the proliferation and migration of A549 cells with concentrations near or higher to 50 μM.

Conclusion: Epigallocatechin gallate's protective effect has been shown in A549 lung adenocarcinoma cells in a time and dose-dependent manner. This suggests the implication of Epigallocatechin gallate for the prevention and therapy for lung cancer.

Background: Cancer chemotherapy with doxorubicin (DOX) has been linked to serious testicular damage and spermatotoxicity due to the induction of oxidative stress, inflammation, and apoptosis. Thus, the current study was carried out to assess the potential ameliorative impact of diosmin, an antioxidant drug, against DOX-mediated spermatoxicity and testicular injury in rats.

Material and methods: In the experimental protocol, rats were grouped into 4: Group 1 received vehicle and saline for 8 weeks while group 2 received diosmin and saline concomitantly for 8 weeks. Group 3 was given 3 mg/kg intraperitoneal DOX once every 7 days for 8 weeks. Group 4 was given 40 mg/kg of diosmin orally for 56 days followed by DOX diosmin administration after one hour. After 56 days of treatment, sperm quality, hormonal testing, biochemical parameters, and histological alterations in the testes were evaluated.

Results: DOX-induced reduce spermatogenic function, testicular 3- and 17β-Hydroxysteroid dehydrogenases, and serum follicle stimulating hormone, luteinizing hormone, and testosterone. It also enhanced inflammation, testicular oxidative damage, and apoptosis. The histopathologic examinations corroborated the biochemical results obtained. Significantly, diosmin treatment reduced DOX-induced injury, as evidenced by restored testicular architecture, increased steroidogenesis, preservation of spermatogenesis, suppression of oxide-inflammatory response, and apoptosis.

Conclusion: It was found that through diosmin antioxidant, anti-apoptotic, and anti-oxido-inflammatory it presents a possible therapeutic alternative for protecting testicular tissue against DOX's harmful effects.

Introduction: Glomerular podocytes are specialized epithelial cells localized to the blood-urine interface of the kidney. Podocyte slit-diaphragm (SD), a size-and-charge-selective junction, is instrumental in blood ultrafiltration and the formation of protein-free urine. The SD consists of macromolecular complexes of several proteins, such as nephrin, podocin, and CD2-associated protein (CD2AP). CD2AP is an adapter protein and is considered to be crucial for the integrity of SD. Mutations in the SD proteins cause nephrotic syndrome (NS), characterized by proteinuria. SD proteins' structural features must be elucidated to understand the mechanism of proteinuria in NS. In this study, we expressed, purified, and biophysically characterized heterologously expressed human CD2AP.

Methods: Codon-optimized human CD2AP was expressed in E. coli Rosetta cells. The recombinant protein was induced with 1 mM IPTG and purified by Ni-NTA affinity chromatography. Analytical size-exclusion chromatography, blue native-PAGE, circular dichroism, and fluorescence spectroscopy were performed to decipher the oligomeric nature, secondary structural content, and tertiary packing of CD2AP.

Results: Our analysis revealed that CD2AP adopts a predominantly disordered secondary structure despite exhibiting moderate tertiary packing, characterized by low helical and β-sheet content. CD2AP readily assembles into homo-oligomers, with octamers and tetramers constituting the primary population. Interestingly, the inherent flexibility of CD2AP's secondary structural elements appears resistant to thermal denaturation. Frameshift mutation (p.K579Efs*7) that leads to loss of the coiled-coil domain promotes aberrant oligomerization of CD2AP through SH3 domains.

Conclusion: We successfully expressed full-length human CD2AP in a heterologous system, wherein the secondary structure of CD2AP is predominantly disordered. CD2AP can form higher-order oligomers, and the significance of these oligomers and the impact of mutations in the context of size-selective permeability of SD needs further investigation.

Background: Diabetic nephropathy (DN) is a prevalent and chronic, severe complication of diabetes, representing a serious global health concern. Early detection of DN is essential for initiating timely and effective therapeutic interventions and accurately assessing prognosis. Neutrophil Gelatinase-Associated Lipocalin (NGAL), a low molecular weight protein, has emerged as a potential biomarker for DN due to its association with renal injury and its ability to provide early indications of kidney damage. NGAL levels in both serum and urine are elevated in individuals with renal damage, making it a valuable biomarker for detecting early signs of kidney impairment in the context of diabetes. This study aims to investigate the utility of NGAL as an early biomarker for DN and explore its correlation with various clinical parameters associated with the disease. Understanding the relationship between NGAL levels and clinical parameters such as glycemic control, renal function, blood pressure, and duration of diabetes is crucial for comprehensively evaluating the potential of NGAL as a diagnostic and prognostic tool for DN. Furthermore, assessing the sensitivity and specificity of NGAL in detecting early-stage DN will provide valuable insights into its clinical applicability and reliability.

Methodology: A planned meta-analysis was conducted following PRISMA and MOOSE guidelines. The PubMed database was searched from January 2016 to June 2023 for English-language studies on DN and NGAL. Fifteen eligible studies were included as per the criteria. Data on serum NGAL levels in DN patients and healthy controls were analyzed using Stata 16.0 software.

Result: The study revealed a significantly higher mean serum NGAL level in DN patients (168.08 ng/ml, 95% CI: 105.50-230.67) compared to healthy controls (75.02 ng/ml, 95% CI: 43.02-107.03), demonstrating NGAL's potential as a biomarker (P=0.01).

Conclusion: NGAL offers a powerful tool for DN diagnosis, staging, and monitoring, surpassing traditional markers in sensitivity. Challenges include defining universal threshold values and ensuring consistent test performance across diverse clinical settings. The study underscores NGAL's potential in transforming DN diagnosis and management.