Biochemical Analysis Research Articles

Assessment of Nutritional status, Anthropometry and Sleep patterns of the Obese patients during pre and post COVID-19 Illness

Background and aimsUntil COVID-19, obesity was the main pandemic of 21 century. To date, there have been 767984989 confirmed cases, and 6943390 include death cases of COVID-19 (WHO). To find the prevalence of Obesity among adults, to adjudge the attitude and behavior of selected subjects towards eating healthy and weight loss during pre- and post-COVID-19. MethodologySubject selection was done through non-probability judgemental sampling. Initially, 70 young adults between 18 - 39 years of age were selected from different localities of Delhi (NCR). The study was conducted based on a questionnaire developed for the survey. Based on the inclusion criteria only 50 subjects were selected for further study. The study was constructed into three phases and the arrangement of subjects was elaborated as under. Phase 1 includes field study, clinical examination, and biochemical analysis, phase II includes the division of experimental and control groups, whereas Phase III includes the pre& post-COVID nutritional status, anthropometric assessment, beverage consumption, and sleep patterns were also assessed. ResultThe nutrition intervention in E3 (balanced diet + nutrient supplement) showed a significant difference with the control group followed by E2 (nutrient supplement) and E1 (balanced diet). Our findings showed that the subjects have Calorie, protein, fat, carbohydrates, sodium, and potassium intake significantly decreased (P= <0.001) during post-intervention, whereas, the fiber, vitamin A, vitamin C, and iron (P= <0.001), and calcium (p=0.006), intake significantly increased during post-intervention. The changes in anthropometric parameters such as waist-to-hip ratio (WHR), body mass index (BMI), and fat% for pre-COVID-19 were higher for both men and women, but after following the dietary recommendation and physical activity found a significant reduction in WHR, BMI, and fat% (P= <0.001) for both men and women. The p-value for subjective sleep quality, sleep latency, habitual sleep efficiency, sleep disturbances, and daytime dysfunction appears to be less than 0.05 which shows that it is significant. The daily consumption of various beverages listed above with a comparison of pre-post intervention, which shows that only for kada the p-value is 0.001 which is less than 0.05 hence it seems significant. The p-value for people with no comorbidity appears less than 0.05, indicating it is significant. majority of participants (12%) with diabetes took comparatively longer than the participants suffering from other comorbidities followed by Hypertension (7%), Hyperthyroidism (4%), Hypothyroidism, and polycystic ovarian disease (PCOD) (3% each) respectively. ConclusionIn the present study, we provided survey data about the key aspects of the nutritional management of COVID-19 (pre-and-post), based on the current knowledge.

Gene Expression, Oxidative Stress, and Neurotransmitters in Rotenone-induced Parkinson’s Disease in Rats: Role of Naringin from Citrus aurantium via Blocking Adenosine A2A Receptor

Background:: Lack of control in voluntary movements, resting tremor, postural instability, and stiffness are the hallmarks of Parkinson's disease (PD). Objective:: The current work's objective is to assess naringin isolated from Citrus aurantium L. peels as an anti-parkinsonism agent in rats. Methods:: The HPLC and LC-ESI-MS analysis of Citrus aurantium L. peels methanol extract was done. The behavioral, biochemical, genetic, and histopathological analysis were evaluated in parkinsonism rats. Results:: Fourteen phenolics and nine flavonoids were found in the extract, according to the HPLC analysis, while LC-ESI-MS analysis revealed the presence of twenty-six flavonoids. The dominant flavonoid subclasses were 4 aglycones, 11 monoglycosides, 5 diglycosides, and 6 polymethoxy flavonoids, beside 4 coumarines, 4 alkaloids and a limonin triterpene. Adenosine A2A receptor (A2AR) gene expression, malondialdehyde (MDA), interleukin-6 (IL-6), caspase-3 (Cas-3) and DNA fragmentation levels significantly increased in rotenone-treated rats. Dopamine (DA), norepinephrine (NE), serotonin (5-HT), reduced glutathione (GSH), succinate, and lactate dehydrogenase (SDH &amp;LDH) levels all significantly decreased. Treatment with naringin and A2AR antagonists enhanced the animals’ behavior and improved all the selected parameters. The brain hippocampal features confirmed our results. Conclusion:: Naringin could be considered a nutraceutical agent by attenuating the neurodegeneration associated with PD via blocking adenosine A2AR.

Altering plasma lipids and liver enzyme activities via hippocampal injections of hen Lysozyme amyloid aggregates in an Alzheimer's disease mouse model: Insights into the therapeutic role of Bis (Indolyl) phenylmethane.

Alzheimer's disease (AD) is a prevalent form of dementia in the elderly. There is currently no effective treatment available for this disease. Diagnosis of AD typically relies on clinical manifestations and specific biomarkers. The present study investigated the impact of inducing Alzheimer's disease (AD) in mice through the injection of lysozyme amyloids formed in the presence or absence of Bis (Indolyl) phenylmethane (BIPM) on alterations in plasma lipid profiles and liver enzyme activities. 24 adult Wistar rats were divided into control, Scopolamine, Lysozyme, BIPM groups and the blood samples were obtained from the groups for biochemical analysis. The findings of the study revealed significant changes in the plasma lipid profiles and liver enzyme markers of the Lysozyme group compared to the control group. The Lysozyme group exhibited elevated triglycerides (n=6, P<0.02) and LDL levels (n=6, P<0.02), reduced HDL (n=6, P<0.05) and cholesterol levels (n=6, P<0.02), and altered serum glutamic oxaloacetic transaminase (SGOT) level (n=6, P<0.05) compared to controls. While the level of serum glutamic pyruvic transaminase (SGPT) did not change significantly compared to the control. BIPM groups showed no significant changes in lipid or enzyme levels compared to controls. Overall, our research has shown that BIPM has the ability to modify the structure of HEWL aggregates, thereby improving the detrimental effects associated with AD caused by these aggregates. Analyzing lipid profiles and liver enzyme markers presents a promising avenue for targeted therapeutic approaches. These alterations observed in the plasma may potentially serve as candidate biomarkers for diagnosing this disease.

Diagnostic utility of selected faecal biochemical parameters in the determination of acute diarrhoea and associated defecation stooling characteristics in dogs: An observational study.

Diarrhoea, which is a clinical manifestation of various illnesses, is frequently observed in dogs. Regrettably, many dog owners find it difficult to provide comprehensive case histories, primarily because of limited interaction with their canine companions. This study aimed to evaluate the potential of faecal biochemical analytes in detecting and characterizing acute diarrhoea in dogs. Sixty-two domestic dogs were selected using the proportionate stratified sample technique. A structured questionnaire was used to collect demographic and clinical data. Faecal stool specimens from the dogs were obtained using the colon flush technique. The specimens were taken through biochemical analysis to determine urea, creatinine, total bilirubin, total cholesterol, triglycerides, gamma-glutamyl transferase and uric acid levels. Results showed a significant association between the diarrhoea status of the participants and their age, weight, breed, body size, source of last diet, period of inappetence, and other gastrointestinal signs (p < 0.050, respectively). Dogs that had not eaten in at least three days were five times more likely (p < 0.05) to have diarrhoea. Furthermore, miniature breeds were about six times more likely to develop diarrhoea (p < 0.05). Of the seven selected biochemical parameters, total faecal cholesterol was the most predictive index in diagnosing acute diarrhoea in dogs, with a likelihood ratio of 6.5, and it was the most accurate in predicting defecation stooling frequency and texture. In summary, in situations of inadequate case histories, measuring total faecal cholesterol could assist veterinarians in detecting diarrhoea and predicting its faecal stooling texture and frequency in dogs.

Proteomics analysis of coronary atherosclerotic heart disease with different Traditional Chinese Medicine syndrome types before and after percutaneous coronary intervention.

To investigate the underlying protein molecular mechanisms of "Qi stagnation and blood stasis syndrome" (QS) and "Qi deficiency and blood stasis syndrome" (QD), as two subtypes of coronary artery disease (CAD) in Traditional Chinese Medicine (TCM), following percutaneous coronary intervention (PCI). In this study, a total of 227 CAD patients with QS and 211 CAD patients with QD were enrolled; all participants underwent PCI. Label-free quantification proteomics were employed to analyze the changes in serum in two subtypes of CAD patients before and 6 months after PCI, aiming to elucidate the intervention mechanism of PCI in treating CAD characterized by two different TCM syndromes. Biochemical analysis revealed significant changes in tumor necrosis factor-α, high density lipoprotein cholesterol, blood stasis clinical symptoms observation, and Gensini levels in both patient groups post-PCI; Proteomic analysis identified 79 and 95 differentially expressed proteins in the QS and QD patient groups, respectively, compared to their control groups. complement C8 alpha chain, complement factor H, apolipoprotein H, apolipoprotein B, plasminogen, carbonic anhydrase 2, and complement factor I were altered in both comparison groups. Furthermore, enrichment analysis demonstrated that cell adhesion and connectivity-related processes underwent changes in QS patients post-PCI, whereas lipid metabolism-related pathways, including the peroxisome proliferator-activated receptor signaling pathway and extracellular matrix receptor interaction, underwent changes in the QD group. The protein-protein interaction network analysis further enriched 52 node proteins, including apolipoprotein B, lipoprotein (a), complement C5, apolipoprotein A4, complement C8 alpha chain, complement C8 beta chain, complement C8 gamma chain, apolipoprotein H, apolipoprotein A-Ⅱ, albumin, complement C4-B, apolipoprotein C3, among others. The functional network of these proteins is posited to contribute to the pathophysiology of CAD characterized by TCM syndromes. The current quantitative proteomic study has preliminarily identified biomarkers of CAD in different TCM subtypes treated with PCI, potentially laying the groundwork for understanding the protein profiles associated with the treatment of various TCM subtypes of CAD.

Dihydroartemisinin alleviates doxorubicin-induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy.

Although the use of Doxorubicin (Dox) is extensive in the treatment of malignant tumor, the toxic effects of Dox on the heart can cause myocardial injury. Therefore, it is necessary to find an alternative drug to alleviate the Dox-induced cardiotoxicity. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin, which is an active ingredient of Artemisia annua. The study investigates the effects of DHA on doxorubicin-induced cardiotoxicity and ferroptosis, which are related to the activation of Nrf2 and the regulation of autophagy. Different concentrations of DHA were administered by gavage for 4 weeks in mice. H9c2 cells were pretreated with different concentrations of DHA for 24 h invitro. The mechanism of DHA treatment was explored through echocardiography, biochemical analysis, real-time quantitative PCR, western blotting analysis, ROS/DHE staining, immunohistochemistry, and immunofluorescence. Invivo, DHA markedly relieved Dox-induced cardiac dysfunction, attenuated oxidative stress, alleviated cardiomyocyte ferroptosis, activated Nrf2, promoted autophagy, and improved the function of lysosomes. Invitro, DHA attenuated oxidative stress and cardiomyocyte ferroptosis, activated Nrf2, promoted clearance of autophagosomes, and reduced lysosomal destruction. The changes of ferroptosis and Nrf2 depend on selective degradation of keap1 and recovery of lysosome. We found for the first time that DHA could protect the heart from the toxic effects of Dox-induced cardiotoxicity. In addition, DHA significantly alleviates Dox-induced ferroptosis through the clearance of autophagosomes, including the selective degradation of keap1 and the recovery of lysosomes.

Isolation, characterization and identification of root nodule bacteria from Macrotyloma uniflorum (Lam.) Verdc

The present study was conducted to characterize the native plant growth promoting rhizobacteria (PGPRs) from the nodules of Macrotyloma uniflorum (Lam.) Verdc. The seeds of Macrotyloma uniflorum was grown in two different soils i.e., sterile and non-sterile soil and four bacterial isolates were isolated. The bacterial isolates were characterised on the basis of morphological and different biochemical analysis. Phylogenetic identification was done on the basis of 16S rRNA analysis. Four isolates obtained belongs to Bacillus velezensis and Enterobacter cloacae.

Biological effects of corticosteroids on pneumococcal pneumonia in Mice—translational significance

BackgroundStreptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The primary objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in a mouse model. A secondary objective was to identify shared transcriptomic features of pneumococcal pneumonia and steroid treatment in the mouse model and clinical samples.MethodsWe carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy. We also studied lower respiratory tract gene expression from a cohort of 15 mechanically ventilated patients (10 with Streptococcus pneumoniae and 5 controls) to compare with the transcriptional studies in the mice.ResultsIn mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden. Transcriptomic analyses identified effects of steroid therapy in mice that were also observed in the clinical samples.ConclusionsIn combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The transcriptional studies in patients suggest that the mouse model replicates some of the features of pneumonia in patients with Streptococcus pneumoniae and steroid treatment. Overall, these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae.

Effects of pleiotropic ompR and envZ alleles of Escherichia coli on envelope stress and antibiotic sensitivity.

The EnvZ-OmpR two-component system of Escherichia coli regulates the expression of the ompF and ompC porin genes in response to medium osmolarity. However, certain mutations in envZ confer pleiotropy by affecting the expression of genes of the iron and maltose regulons not normally controlled by EnvZ-OmpR. In this study, we obtained two novel envZ and ompR pleiotropic alleles, envZT15P and ompRL19Q, among revertants of a mutant with heightened envelope stress and an outer membrane (OM) permeability defect. Unlike envZ, pleiotropic mutations in ompR have not been described previously. The mutant alleles reduced the expression of several outer membrane proteins (OMPs), overcame the temperature-sensitive growth defect of a protease-deficient (ΔdegP) strain, and lowered envelope stress and OM permeability defects in a background lacking the BamB protein of an essential β-barrel assembly machinery complex. Biochemical analysis showed OmpRL19Q, like wild-type OmpR, is readily phosphorylated by EnvZ, but the EnvZ-dependent dephosphorylation of OmpRL19Q~P was drastically impaired compared to wild-type OmpR. This defect would lead to a prolonged half-life for OmpRL19Q~P, an outcome remarkably similar to what we had previously described for EnvZR397L, resulting in pleiotropy. By employing null alleles of the OMP genes, it was determined that the three pleiotropic alleles lowered envelope stress by reducing OmpF and LamB levels. The absence of LamB was principally responsible for lowering the OM permeability defect, as assessed by the reduced sensitivity of a ΔbamB mutant to vancomycin and rifampin. Possible mechanisms by which novel EnvZ and OmpR mutants influence EnvZ-OmpR interactions and activities are discussed.IMPORTANCEMaintenance of the outer membrane (OM) integrity is critical for the survival of Gram-negative bacteria. Several envelope homeostasis systems are activated when OM integrity is perturbed. Through the isolation and characterization of novel pleiotropic ompR/envZ alleles, this study highlights the involvement of the EnvZ-OmpR two-component system in lowering envelope stress and the OM permeability defect caused by the loss of proteins that are involved in OM biogenesis, envelope homeostasis, and structural integrity.

A comparative biochemical characterization of Allium genetic resources of Türkiye

AbstractThe present study aimed to determine the variation in onion and garlic genetic resources collected from the Kelkit Valley, a unique biodiversity concerved region in Türkiye. For this purpose, 17 onion genotypes and 12 garlic genotypes were collected from local growers. A total of 9 biochemical analyses (total phenolic matter, total soluble protein, total dry matter, total flavonoid matter, ferric reducing antioxidant power, cupric reducing antioxidant capacity, 2,2-diphenyl-1-picrylhydrazylradical scavenging activity, hydrogen peroxide scavenging capacity and ascorbic acid) were performed on bulb and leaf extracts of all genotypes. According to variance analysis of the biochemical results from the samples, the differences between genotypes for all parameters were found to be significant (p &lt; 0.05). A post-hoc test (Tukey) and multiple means comparison were performed to analyze the results between groups in cases of significant differences. The results indicated that there is a large variation between different genotypes of both species and between both species and organs.

XPD stalled on cross-linked DNA provides insight into damage verification.

The superfamily 2 helicase XPD is a central component of the general transcription factor II H (TFIIH), which is essential for transcription and nucleotide excision DNA repair (NER). Within these two processes, the helicase function of XPD is vital for NER but not for transcription initiation, where XPD acts only as a scaffold for other factors. Using cryo-EM, we deciphered one of the most enigmatic steps in XPD helicase action: the active separation of double-stranded DNA (dsDNA) and its stalling upon approaching a DNA interstrand cross-link, a highly toxic form of DNA damage. The structure shows how dsDNA is separated and reveals a highly unusual involvement of the Arch domain in active dsDNA separation. Combined with mutagenesis and biochemical analyses, we identified distinct functional regions important for helicase activity. Surprisingly, those areas also affect core TFIIH translocase activity, revealing a yet unencountered function of XPD within the TFIIH scaffold. In summary, our data provide a universal basis for NER bubble formation, XPD damage verification and XPG incision.

Dental service utilization in the general adult population in Bangladesh.

With the help of a national community-based survey, the analysis aimed to estimate the number of adults in Bangladesh who used dental services (DSU). The 8185 participants (18-69 years old) in the Bangladesh cross-sectional STEPS survey in 2018 provided national data for analysis. Predisposing, enabling, and need factors for DSU were included in the interview data, physical examinations, and biochemical analyses. To estimate the DSU (last 12 months) predictors, Poisson regression was employed. Seven out of 10 participants (71.0%) had never DSU, 13.2% within the past 12 months, and 15.9% more than 12 months ago. In terms of predisposing factors, the final model showed a negative relationship between past 12-month DSU and living in the northern region (adjusted prevalence ratio-APR: 0.75, 95% CI: 0.59, 0.96). The enabling factors of living in an urban area (APR: 1.19, 95% CI: 1.01, 1.41) and seeing a doctor or other healthcare provider within the previous year (APR: 1.37, 95% CI: 1.08, 1.74) were positively correlated with DSU. In terms of need factors, dental pain (APR: 15.37, 95% CI: 9.68, 24.40), multimorbidity (APR: 1.26, 95% CI: 1.02, 1.55), oral health impact (OHI) speech problem (APR: 1.35, 95% CI: 1.13, 1.63), and OHI felt tense (APR: 1.34, 95% CI: 1.10, 1.64) were positively associated with DSU. A low proportion of participants had DSU in the past 12 months and several associated factors were identified.

Genomic and phenotypic characterization of 26 novel marine bacterial strains with relevant biogeochemical roles and widespread presence across the global ocean

Prokaryotes dominate global oceans and shape biogeochemical cycles, yet most taxa remain uncultured and uncharacterized as of today. Here we present the characterization of 26 novel marine bacterial strains from a large isolate collection obtained from Blanes Bay (NW Mediterranean) microcosm experiments made in the four seasons. Morphological, cultural, biochemical, physiological, nutritional, genomic, and phylogenomic analyses were used to characterize and phylogenetically place the novel isolates. The strains represent 23 novel bacterial species and six novel genera: three novel species pertaining to class Alphaproteobacteria (families Rhodobacteraceae and Sphingomonadaceae), six novel species and three new genera from class Gammaproteobacteria (families Algiphilaceae, Salinispheraceae, and Alteromonadaceae), 13 novel species and three novel genera from class Bacteroidia (family Flavobacteriaceae), and one new species from class Rhodothermia (family Rubricoccaceae). The bacteria described here have potentially relevant roles in the cycles of carbon (e.g., carbon fixation or energy production via proteorhodopsin), nitrogen (e.g., denitrification or use of urea), sulfur (oxidation of sulfur compounds), phosphorus (acquisition and use of different forms of phosphorus and remodeling of membrane phospholipids), and hydrogen (oxidation of hydrogen to obtain energy). We mapped the genomes of the presented strains to the Tara Oceans metagenomes to reveal that these strains were globally distributed, with those of the family Flavobacteriaceae being the most widespread and abundant, while Rhodothermia being the rarest and most localized. While molecular-only approaches are also important, our study stresses the importance of culturing as a powerful tool to further understand the functioning of marine bacterial communities.

Mitochondrial Aldehyde Dehydrogenase 2 (ALDH2) Protects against Binge Alcohol-Mediated Gut and Brain Injury

Mitochondrial aldehyde dehydrogenase-2 (ALDH2) metabolizes acetaldehyde to acetate. People with ALDH2 deficiency and Aldh2-knockout (KO) mice are more susceptible to alcohol-induced tissue damage. However, the underlying mechanisms behind ALDH2-related gut-associated brain damage remain unclear. Age-matched young female Aldh2-KO and C57BL/6J wild-type (WT) mice were gavaged with binge alcohol (4 g/kg/dose, three doses) or dextrose (control) at 12 h intervals. Tissues and sera were collected 1 h after the last ethanol dose and evaluated by histological and biochemical analyses of the gut and hippocampus and their extracts. For the mechanistic study, mouse neuroblast Neuro2A cells were exposed to ethanol with or without an Aldh2 inhibitor (Daidzin). Binge alcohol decreased intestinal tight/adherens junction proteins but increased oxidative stress-mediated post-translational modifications (PTMs) and enterocyte apoptosis, leading to elevated gut leakiness and endotoxemia in Aldh2-KO mice compared to corresponding WT mice. Alcohol-exposed Aldh2-KO mice also showed higher levels of hippocampal brain injury, oxidative stress-related PTMs, and neuronal apoptosis than the WT mice. Additionally, alcohol exposure reduced Neuro2A cell viability with elevated oxidative stress-related PTMs and apoptosis, all of which were exacerbated by Aldh2 inhibition. Our results show for the first time that ALDH2 plays a protective role in binge alcohol-induced brain injury partly through the gut–brain axis, suggesting that ALDH2 is a potential target for attenuating alcohol-induced tissue injury.

ESAT-6 undergoes self-association at phagosomal pH and an ESAT-6-specific nanobody restricts M. tuberculosis growth in macrophages.

Mycobacterium tuberculosis (Mtb) is known to survive within macrophages by compromising the integrity of the phagosomal compartment in which it resides. This activity primarily relies on the ESX-1 secretion system, predominantly involving the protein duo ESAT-6 and CFP-10. CFP-10 likely acts as a chaperone, while ESAT-6 likely disrupts phagosomal membrane stability via a largely unknown mechanism. we employ a series of biochemical analyses, protein modeling techniques, and a novel ESAT-6-specific nanobody to gain insight into the ESAT-6's mode of action. First, we measure the binding kinetics of the tight 1:1 complex formed by ESAT-6 and CFP-10 at neutral pH. Subsequently, we demonstrate a rapid self-association of ESAT-6 into large complexes under acidic conditions, leading to the identification of a stable tetrameric ESAT-6 species. Using molecular dynamics simulations, we pinpoint the most probable interaction interface. Furthermore, we show that cytoplasmic expression of an anti-ESAT-6 nanobody blocks Mtb replication, thereby underlining the pivotal role of ESAT-6 in intracellular survival. Together, these data suggest that ESAT-6 acts by a pH-dependent mechanism to establish two-way communication between the cytoplasm and the Mtb-containing phagosome.

Pathological Changes and Metabolic Adaptation in the Myocardium of Rats in Response to Chronic Variable Mild Stress

Chronic variable mild stress (CVS) in rats is a well-established paradigm for inducing depressive-like behaviors and has been utilized extensively to explore potential therapeutic interventions for depression. While the behavioral and neurobiological effects of CVS have been extensively studied, its impact on myocardial function remains largely unexplored. To induce the CVS model, rats were exposed to various stressors over 40 days. Behavioral assessments confirmed depressive-like behavior. Biochemical analyses revealed alterations in myocardial metabolism, including changes in NAD+ and NADP+, and NADPH concentrations. Free amino acid analysis indicated disturbances in myocardial amino acid metabolism. Evaluation of oxidative DNA damage demonstrated an increased number of abasic sites in the DNA of rats exposed to CVS. Molecular analysis showed significant changes in gene expression associated with glucose metabolism, oxidative stress, and cardiac remodeling pathways. Histological staining revealed minor morphological changes in the myocardium of CVS-exposed rats, including increased acidophilicity of cells, collagen deposition surrounding blood vessels, and glycogen accumulation. This study provides novel insights into the impact of chronic stress on myocardial function and metabolism, highlighting potential mechanisms linking depression and cardiovascular diseases. Understanding these mechanisms may aid in the development of targeted therapeutic strategies to mitigate the adverse cardiovascular effects of depression.

ESAT-6 undergoes self-association at phagosomal pH and an ESAT-6-specific nanobody restricts M. tuberculosis growth in macrophages

Mycobacterium tuberculosis (Mtb) is known to survive within macrophages by compromising the integrity of the phagosomal compartment in which it resides. This activity primarily relies on the ESX-1 secretion system, predominantly involving the protein duo ESAT-6 and CFP-10. CFP-10 likely acts as a chaperone, while ESAT-6 likely disrupts phagosomal membrane stability via a largely unknown mechanism. we employ a series of biochemical analyses, protein modeling techniques, and a novel ESAT-6-specific nanobody to gain insight into the ESAT-6’s mode of action. First, we measure the binding kinetics of the tight 1:1 complex formed by ESAT-6 and CFP-10 at neutral pH. Subsequently, we demonstrate a rapid self-association of ESAT-6 into large complexes under acidic conditions, leading to the identification of a stable tetrameric ESAT-6 species. Using molecular dynamics simulations, we pinpoint the most probable interaction interface. Furthermore, we show that cytoplasmic expression of an anti-ESAT-6 nanobody blocks Mtb replication, thereby underlining the pivotal role of ESAT-6 in intracellular survival. Together, these data suggest that ESAT-6 acts by a pH-dependent mechanism to establish two-way communication between the cytoplasm and the Mtb-containing phagosome.

Pin1 Exacerbates Non-Alcoholic Fatty Liver Disease by Enhancing Its Activity through Binding to ACC1

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by diffuse hepatocellular steatosis due to fatty deposits in hepatocytes, excluding alcohol and other known liver injury factors. However, there are no specific drugs for the clinical treatment of NAFLD. Therefore, research on the pathogenesis of NAFLD at the cellular and molecular levels is a promising approach to finding therapeutic targets and developing targeted drugs for NAFLD. Pin1 is highly expressed during adipogenesis and contributes to adipose differentiation, but its specific mechanism of action in NAFLD is unclear. In this study, we investigated the role of Pin1 in promoting the development of NAFLD and its potential mechanisms in vitro and in vivo. First, Pin1 was verified in the NAFLD model in vitro using MCD diet-fed mice by Western Blot, RT-qPCR and immunohistochemistry (IHC) assays. In the in vitro study, we used the oleic acid (OA) stimulation-induced lipid accumulation model and examined the lipid accumulation in each group of cells by oil red O staining as well as BODIPY staining. The results showed that knockdown of Pin1 inhibited lipid accumulation in hepatocytes in an in vitro lipid accumulation model and improved lipid indices and liver injury levels. Moreover, in vivo, WT and Pin1-KO mice were fed a methionine-choline deficient (MCD) diet for 4 weeks to induce the NAFLD model. The effects of Pin1 on lipid accumulation, hepatic fibrosis, and oxidative stress were evaluated by biochemical analysis, glucose and insulin tolerance tests, histological analysis, IHC, RT-qPCR and Western blot assays. The results indicate that Pin1 knockdown significantly alleviated hepatic steatosis, fibrosis and inflammation in MCD-induced NAFLD mice, improved glucose tolerance and alleviated insulin resistance in mice. Further studies showed that the AMPK/ACC1 signalling pathway might take part in the process by which Pin1 regulates NAFLD, as evidenced by the inhibition of the AMPK/ACC1 pathway. In addition, immunofluorescence (IF), coimmunoprecipitation (Co-IP) and GST pull-down experiments also showed that Pin1 interacts directly with ACC1 and inhibits ACC1 phosphorylation levels. Our study suggests that Pin1 promotes NAFLD progression by inhibiting the activation of the AMPK/ACC1 signalling pathway, and it is possible that this effect is achieved by Pin1 interacting with ACC1 and inhibiting the phosphorylation of ACC1.

Protective Effects of Iraqi Propolis on Carbimazole-Induced Reduction of Sex Hormones in Female Adult Rats

Background:: Propolis (PR) is used as a health supplement and is widely used in foods and drinks in many parts of the world. This study aimed to know the possible reproductive toxicity effect of the antithyroid drug carbimazole (CZ) in adult female albino rats and to evaluate the possible protective role of Iraqi PR. Methods:: Twenty-four adult female albino rats were randomized into four groups: control, PR, CZ, and PR + CZ. Rats were orally treated for six weeks. Ovarian biochemical and histopathological analyses were performed. Results:: No change in appearance, no signs of toxicity, and no deaths of animals were reported throughout the study period. There was a significant body weight increase only in the PR group. The CZ group displayed a reduction in serum T3 and T4 levels and a rise in serum TSH levels compared to the control. Also, there was a significant decrease in serum T3, T4, and TSH levels after exposure to PR+ CZ compared to control. Exposure to 0.01mg/g body weight of CZ for six weeks results in a significant reduction of serum LH, FSH, and estradiol (E2) in female rats. At the same time, PR alone or with CZ was found to have no significant effect. Biochemical results were consistent with histopathological results. Conclusion:: Iraqi PR provides a protective effect against the reduction of serum sex hormones induced by CZ. Further studies are required to confirm this effect. PR has no effect on CZ activity in reducing thyroxin levels; however, PR might reduce the effects of CZ on TSH levels. Furthermore, PR alone demonstrated an elevation in the weight gain of animals compared to the control group.

Phenotypical and biochemical characterization of tomato plants treated with triacontanol.

Biostimulants are heterogeneous products designed to support plant development and to improve the yield and quality of crops. Here, we focused on the effects of triacontanol, a promising biostimulant found in cuticle waxes, on tomato growth and productivity. We examined various phenological traits related to vegetative growth, flowering and fruit yield, the metabolic profile of fruits, and the response of triacontanol-treated plants to salt stress. Additionally, a proteomic analysis was conducted to clarify the molecular mechanisms underlying triacontanol action. Triacontanol application induced advanced and increased blooming without affecting plant growth. Biochemical analyses of fruits showed minimal changes in nutritional properties. The treatment also increased the germination rate of seeds by altering hormone homeostasis and reduced salt stress-induced damage. Proteomics analysis of leaves revealed that triacontanol increased the abundance of proteins related to development and abiotic stress, while down-regulating proteins involved in biotic stress resistance. The proteome of the fruits was not significantly affected by triacontanol, confirming that biostimulation did not alter the nutritional properties of fruits. Overall, our findings provide evidence of the effects of triacontanol on growth, development, and stress tolerance, shedding light on its mechanism of action and providing new insights into its potential in agricultural practices.