Pro- and anti-inflammatory cytokines are the game-changers in childhood obesity-associated metabolic disorders (diabetes and non-alcoholic fatty liver diseases).

Childhood obesity is a chronic inflammatory epidemic that affects children worldwide. Obesity affects approximately 1 in 5 children worldwide. Obesity in children can worsen weight gain and raise the risk of obesity-related comorbidities like diabetes and non-alcoholic fatty liver disease (NAFLD). It can also negatively impact the quality of life for these children. Obesity disrupts immune system function, influencing cytokine (interleukins) balance and expression levels, adipokines, and innate and adaptive immune cells. The altered expression of immune system mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17 (IL-17), interleukin-18 (IL-18), transforming growth factor (TGF), tumor necrosis factor (TNF), and others, caused inflammation, progression, and the development of pediatric obesity and linked illnesses such as diabetes and NAFLD. Furthermore, anti-inflammatory cytokines, including interleukin-2 (IL-2), have been shown to have anti-diabetes and IL-1 receptor antagonist (IL-1Ra) anti-diabetic and pro-NAFLFD properties, and interleukin-10 (IL-10) has been shown to have a dual role in managing diabetes and anti-NAFLD. In light of the substantial increase in childhood obesity-associated disorders such as diabetes and NAFLD and the absence of an effective pharmaceutical intervention to inhibit immune modulation factors, it is critical to consider the alteration of immune system components as a preventive and therapeutic approach. Thus, the current review focuses on the most recent information regarding the influence of pro- and anti-inflammatory cytokines (interleukins) and their molecular mechanisms on pediatric obesity-associated disorders (diabetes and NAFLD). Furthermore, we discussed the current therapeutic clinical trials in childhood obesity-associated diseases, diabetes, and NAFLD.

The role of proinflammatory cytokines and CXC chemokines (CXCL1-CXCL16) in the progression of prostate cancer: insights on their therapeutic management.

Reproductive cancers are malignancies that develop in the reproductive organs. One of the leading cancers affecting the male reproductive system on a global scale is prostate cancer (PCa). The negative consequences of PCa metastases endure and are severe, significantly affecting mortality and life quality for those who are affected. The association between inflammation and PCa has captured interest for a while. Inflammatory cells, cytokines, CXC chemokines, signaling pathways, and other elements make up the tumor microenvironment (TME), which is characterized by inflammation. Inflammatory cytokines and CXC chemokines are especially crucial for PCa development and prognosis. Cytokines (interleukins) and CXC chemokines such as IL-1, IL-6, IL-7, IL-17, TGF-ß, TNF-α, CXCL1-CXCL6, and CXCL8-CXCL16 are thought to be responsible for the pleiotropic effects of PCa, which include inflammation, progression, angiogenesis, leukocyte infiltration in advanced PCa, and therapeutic resistance. The inflammatory cytokine and CXC chemokines systems are also promising candidates for PCa suppression and immunotherapy. Therefore, the purpose of this work is to provide insight on how the spectra of inflammatory cytokines and CXC chemokines evolve as PCa develops and spreads. We also discussed recent developments in our awareness of the diverse molecular signaling pathways of these circulating cytokines and CXC chemokines, as well as their associated receptors, which may one day serve as PCa-targeted therapies. Moreover, the current status and potential of theranostic PCa therapies based on cytokines, CXC chemokines, and CXC receptors (CXCRs) are examined.

Pro-inflammatory cytokines and CXC chemokines as game-changer in age-associated prostate cancer and ovarian cancer: Insights from preclinical and clinical studies' outcomes.

Prostate cancer (PC) and Ovarian cancer (OC) are two of the most common types of cancer that affect the reproductive systems of older men and women. These cancers are associated with a poor quality of life among the aged population. Therefore, finding new and innovative ways to detect, treat, and prevent these cancers in older patients is essential. Finding biomarkers for these malignancies will increase the chance of early detection and effective treatment, subsequently improving the survival rate. Studies have shown that the prevalence and health of some illnesses are linked to an impaired immune system. However, the age-associated changes in the immune system during malignancies such as PC and OC are poorly understood. Recent research has suggested that the excessive production of inflammatory immune mediators, such as interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor (TGF), tumor necrosis factor (TNF), CXC motif chemokine ligand 1 (CXCL1), CXC motif chemokine ligand 12 (CXCL12), and CXC motif chemokine ligand 13 (CXCL13), etc., significantly impact the development of PC and OC in elderly patients. Our review focuses on the latest functional studies of pro-inflammatory cytokines (interleukins) and CXC chemokines, which serve as biomarkers in elderly patients with PC and OC. Thus, we aim to shed light on how these biomarkers affect the development of PC and OC in elderly patients. We also examine the current status and future perspective of cytokines (interleukins) and CXC chemokines-based therapeutic targets in OC and PC treatment for elderly patients.

Network Pharmacology and Molecular Modeling Techniques in Unraveling the Underlying Mechanism of Citri Reticulatae Pericarpium aganist Type 2 Diabetic Osteoporosis.

Type 2 diabetic osteoporosis (T2DOP) is a common complication in diabetic patients that seriously affects their health and quality of life. The pathogenesis of T2DOP is complex, and there are no targeted governance means in modern medicine. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese medicine that has a long history and has been used in the treatment of osteoporosis diseases. However, the molecular mechanism for the CRP treatment of T2DOP is not clear. Therefore, this study aimed to explore the underlying mechanisms of CRP for the treatment of T2DOP by using network pharmacology and molecular modeling techniques. By retrieving multiple databases, we obtained 5 bioactive compounds and 63 common targets of bioactive compounds with T2DOP, and identified AKT 1, TP 53, JUN, BCL 2, MAPK 1, NFKB 1, and ESR 1 as the core targets of their PPI network. Enrichment analysis revealed that these targets were mainly enriched in the estrogen signaling pathway, TNF signaling pathway, and AGE-RAGE signaling pathway in diabetics, which were mainly related to oxidative stress and hormonal regulation. Molecular docking and molecular dynamics simulations have shown the excellent binding effect of the bioactive compounds of CRP and the core targets. These findings reveal that CRP may ameliorate T2DOP through multiple multicomponent and multitarget pathways.

A computational quest for identifying potential vaccine candidates against Moraxella lacunata: a multi-pronged approach.

Moraxella lacunata is an emerging gram-negative bacterium that is responsible for multiple nosocomial infections. The bacterium is evolving resistance to several antibiotics, and currently, no effective licensed vaccines are available, which warrants the search for new therapeutics. A multi-epitope-based vaccine has been designed for M. lacunata. The complete proteome of M. lacunata contains 10,110 core proteins. Subcellular localization analysis revealed the presence of five proteins in the extracellular matrix, while 19 proteins were predicted to be located in the outer membrane, and 21 proteins were predicted to be located in the periplasmic region. Only two proteins, the type VI secretion system tube protein (Hcp) and the transporter substrate-binding domain-containing protein, were selected for epitope prediction as they fulfilled all the criteria for being potential vaccine candidates. Shortlisted epitopes from the selected proteins were fused together using "GPGPG" linkers to overcome the limitations of single-epitope vaccines. Next, the cholera toxin-B adjuvant was attached to the peptide epitope using an EAAAK linker. Docking analysis was performed to examine the interaction between the vaccine and immune cell receptors, revealing robust intermolecular interactions and a stable binding conformation. Molecular dynamics simulation findings revealed no drastic changes in the binding conformation of complexes during the simulation period. The net binding free energy of vaccine-receptor complexes was estimated using the molecular mechanics energies combined with the Poisson-Boltzmann and surface area continuum solvation (MM-PBSA) method. The reported values were -586.38 kcal/mol, -283.74 kcal/mol, and -296.88 kcal/mol for the TLR-4-vaccine complex, MHC-I-vaccine complex, and MHC-II-vaccine complex, respectively. Furthermore, the molecular mechanics energies combined with the generalized Born and surface area continuum solvation (MM-GBSA) analysis predicted binding free energies of -596.69 kcal/mol, -287.39 kcal/mol, and -298.28 kcal/mol for the TLR-4-vaccine complex, MHC-I-vaccine complex, and MHC-II-vaccine complex, respectively. The theoretical vaccine design proposed in the study could potentially serve as a powerful therapeutic against targeted pathogens, subject to validation through experimental studies.Communicated by Ramaswamy H. Sarma.

Involvement of CXC chemokines (CXCL1-CXCL17) in gastric cancer: Prognosis and therapeutic molecules.

Gastric cancer (GC) is the fifth-most prevalent and second-most deadly cancer worldwide. Due to the late onset of symptoms, GC is frequently treated at a mature stage. In order to improve the diagnostic and clinical decision-making processes, it is necessary to establish more specific and sensitive indicators valuable in the early detection of the disease whenever a cancer is asymptomatic. In this work, we gathered information about CXC chemokines and GC by using scientific search engines including Google Scholar, PubMed, SciFinder, and Web of Science. Researchers believe that GC chemokines, small proteins, class CXC chemokines, and chemokine receptors promote GC inflammation, initiation, and progression by facilitating angiogenesis, tumor transformation, invasion, survival, metastatic spread, host response safeguards, and inter-cell interaction. With our absolute best professionalism, the role of CXC chemokines and their respective receptors in GC diagnosis and prognosis has not been fully explained. This review article updates the general characteristics of CXC chemokines, their unique receptors, their function in the pathological process of GC, and their potential application as possible indicators for GC. Although there have only recently been a few studies focusing on the therapeutic efficacy of CXC chemokine inhibitors in GC, growing experimental evidence points to the inhibition of CXC chemokines as a promising targeted therapy. Therefore, further translational studies are warranted to determine whether specific antagonists or antibodies designed to target CXC chemokines alone or in combination with chemotherapy are useful for diagnosing advanced GC.

Synthesis of Silver Nanoparticles from Ganoderma Species and Their Activity against Multi Drug Resistant Pathogens.

The widespread and indiscriminate use of broad-spectrum antibiotics leads to microbial resistance, which causes major problems in the treatment of infectious diseases. However, advances in nanotechnology using mushrooms have opened up new domains for the synthesis and use of nanoparticles against multidrug-resistant pathogens. Mushooms have recently attracted attention and are exploited for food and medicinal purposes. The current study focuses on the molecular identification, characterization of biologically synthesized silver nanoparticles by X-ray diffraction (XRD) spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), UV-Vis spectroscopy and scanning electron microscopy (SEM) and antibacterial analysis of extract and silver nanoparticles (AgNPs) synthesis from Ganoderma resinaceum against multidrug resistant microbes. Accurate identification of mushrooms is key in utilizing them for the benefit of humans. However, morphological identification of mushrooms is time consuming, tedious and may be prone to error. Molecular techniques are quick and reliable tools that are useful in mushroom taxonomy. Blast results showed that G. resinaceum (GU451247) obtained from Pakistan was 97 % same to the recognized G. resinaceum (GU451247) obtained from China as well as G. resinaceum (GU451247) obtained from India. The antimicrobial potential of mushroom composite and AgNPs showed high efficacy against pathogenic Staphylococcus aureus (ZOI 23 mm) K. pneumonia (ZOI 20 mm), Pseudomonas aeruginosa (ZOI 24 mm) and E. fecalis and A. baumannii (ZOI 10 mm), and multidrug resistant (MDR) A. baumannii (ZOI 24 mm). XRD evaluation revealed the crystalline composition of synthesized NPs with diameter of 45 nm. UV-Vis spectroscopy obsorption peaked of 589 nm confirmed the presence of AgNPs. SEM results showed the cubic morphology of AgNPs. The FTIR analysis of NPs obtained from G. resinaceum containing C=O as well as (O=C-H) stretching revealed presence of hydrogen, carbonyl and amide groups. The synthesized extract and AgNPs showed promising minimum inhibitory concentration (MIC) at 2 mg concentration against the MDR strains. AgNPs are observed to be efficient as they need less quantities to prevent bacterial growth. In the view of challenges for developing antimicrobial NPs of variable shape and size by various other methods, tuning nanoparticles synthesized via mushrooms can be a wonderful approach to resolve existing hurdles.

Causal Effect of Selenium Levels on Osteoporosis: A Mendelian Randomization Study.

Prior research has demonstrated equivocal associations between selenium (Se) concentrations and osteoporosis (OP), yielding inconclusive findings. The purpose of the current study was to examine the potential correlation between Se levels and the risk of OP by using the Mendelian randomization (MR) study design. The genetic variants related to Se levels were obtained from a meta-analysis of a Genome-Wide Association Study (GWAS) conducted on toenail Se levels (n = 4162) and blood Se levels (n = 5477). The data summary for OP and bone mineral density (BMD) was obtained by utilizing the GWAS database. To examine the association between Se levels and BMD and OP, we employed three statistical methods: inverse variance weighted, weighted median, and MR-Egger. The reliability of the analysis was verified by sensitivity testing. All three methods of MR analysis revealed that Se levels had no effect on OP risk. In addition, the sensitivity analysis revealed no heterogeneity or pleiotropy, and the significance of the overall effect remained unaffected by single-nucleotide polymorphisms (SNPs), as determined by the leave-one-out analysis, indicating that our findings are relatively reliable. The results of our study indicate that there is no causal association between Se levels and the risk of OP. However, additional investigation is necessary to ascertain whether there is a potential association between these variables.

Pathophysiological impact of CXC and CX3CL1 chemokines in preeclampsia and gestational diabetes mellitus.

Diabetes-related pathophysiological alterations and various female reproductive difficulties were common in pregnant women with gestational diabetes mellitus (GDM), who had 21.1 million live births. Preeclampsia (PE), which increases maternal and fetal morbidity and mortality, affects approximately 3%-5% of pregnancies worldwide. Nevertheless, it is unclear what triggers PE and GDM to develop. Therefore, the development of novel moderator therapy approaches is a crucial advancement. Chemokines regulate physiological defenses and maternal-fetal interaction during healthy and disturbed pregnancies. Chemokines regulate immunity, stem cell trafficking, anti-angiogenesis, and cell attraction. CXC chemokines are usually inflammatory and contribute to numerous reproductive disorders. Fractalkine (CX3CL1) may be membrane-bound or soluble. CX3CL1 aids cell survival during homeostasis and inflammation. Evidence reveals that CXC and CX3CL1 chemokines and their receptors have been the focus of therapeutic discoveries for clinical intervention due to their considerable participation in numerous biological processes. This review aims to give an overview of the functions of CXC and CX3CL1 chemokines and their receptors in the pathophysiology of PE and GDM. Finally, we examined stimulus specificity for CXC and CX3CL1 chemokine expression and synthesis in PE and GDM and preclinical and clinical trials of CXC-based PE and GDM therapies.

Phylogenetic Analysis and Emerging Drug Resistance against Different Nucleoside Analogues in Hepatitis B Virus Positive Patients.

Several nucleotide analogues have been approved for use in treating hepatitis B virus (HBV) infection. Long-term exposure to therapy leads to the emergence of mutations within the HBV DNA polymerase gene, resulting in drug resistance, a major factor contributing to therapy failure. Chronic HBV patients from the Khyber Pakhtunkhwa province, Pakistan, who had completed 6 months of therapy participated in this study. Samples were collected from 60 patients. In this study, the entire reverse transcriptase domain of the HBV polymerase gene was amplified using nested polymerase chain reaction and sequenced. Drug-resistant mutations were detected in nine (22.5%) patients. All of these patients had lamivudine-resistant mutations (rtM204V + L180M), while seven individuals (17.5%) had both lamivudine- plus entecavir-resistant mutations (L180M + M204V + S202G). N236T, a mutation that gives rise to tenofovir and adefovir resistance, was observed in two (5%) patients. T184A, a partial drug-resistant mutation to entecavir, was found in five (12.5%) patients. Furthermore, other genotypic variants (100%) and vaccine escape mutations (5%) were additionally observed. Moreover, pN459Y (35%), pN131D (20%), pL231S (20%), pP130Q (17.5%), pS189Q (12.5%), pP161S (5%), pH160P (2.5%), pT322S (2.5%), and pA223S (2.5%) mutations in the polymerase gene, as well as sA166V (17.5%), sQ181K (12.5%), sV184R (7.5%), sA17E (5%), sP153S/K (5%), sW156C (5%), sC76Y (2.5%), and S132F (2.5%) mutations in the small surface gene, were identified for the first time in this study. Phylogenetic analysis showed that genotype D was predominant amongst the HBV carriers. Subtype D1 was found in most patients, while two patients were subtype D9. These novel findings may contribute to the body of knowledge and have clinical significance for treating and curing HBV infections in Pakistan.

Antibiotic Resistance Profiling and Phylogenicity of Uropathogenic Bacteria Isolated from Patients with Urinary Tract Infections.

Urinary tract infections (UTIs) are healthcare problems that commonly involve bacterial and, in some rare instances, fungal or viral infections. The irrational prescription and use of antibiotics in UTI treatment have led to an increase in antibiotic resistance. Urine samples (145) were collected from male and female patients from Lower Dir, Khyber Pakhtunkhwa (KP), Pakistan. Biochemical analyses were carried out to identify uropathogens. Molecular analysis for the identification of 16S ribosomal RNA in samples was performed via Sanger sequencing. Evolutionary linkage was determined using Molecular Evolutionary Genetics Analysis-7 (MEGA-7). The study observed significant growth in 52% of the samples (83/145). Gram-negative bacteria were identified in 85.5% of samples, while Gram-positive bacteria were reported in 14.5%. The UTI prevalence was 67.5% in females and 32.5% in males. The most prevalent uropathogenic bacteria were Klebsiella pneumoniae (39.7%, 33/83), followed by Escherichia coli (27.7%, 23/83), Pseudomonas aeruginosa (10.8%, 9/83), Staphylococcus aureus (9.6%, 8/83), Proteus mirabilis (7.2%, 6/83) and Staphylococcus saprophyticus (4.8%, 4/83). Phylogenetic analysis was performed using the neighbor-joining method, further confirming the relation of the isolates in our study with previously reported uropathogenic isolates. Antibiotic susceptibility tests identified K. pneumonia as being sensitive to imipenem (100%) and fosfomycin (78.7%) and resistant to cefuroxime (100%) and ciprofloxacin (94%). Similarly, E. coli showed high susceptibility to imipenem (100%), fosfomycin (78.2%) and nitrofurantoin (78.2%), and resistance to ciprofloxacin (100%) and cefuroxime (100%). Imipenem was identified as the most effective antibiotic, while cefuroxime and ciprofloxacin were the least. The phylogenetic tree analysis indicated that K. pneumoniae, E. coli, P. aeruginosa, S. aureus and P. mirabilis clustered with each other and the reference sequences, indicating high similarity (based on 16S rRNA sequencing). It can be concluded that genetically varied uropathogenic organisms are commonly present within the KP population. Our findings demonstrate the need to optimize antibiotic use in treating UTIs and the prevention of antibiotic resistance in the KP population.

Association of diet quality with the risk of Sarcopenia based on the Chinese diet balance index 2016: a cross-sectional study among Chinese adults in Henan Province.

BACKGROUND: Sarcopenia can lead to a series of unfavourable health outcomes. Diet is an important factor influencing sarcopenia. In this study, we aimed to evaluate the association of sarcopenia with diet quality assessed by the Chinese Diet Balance Index 2016 (DBI-16). METHODS: A cross-sectional study was conducted to collect information on nutrition and health in Henan Province, China, and a total of 644 individuals were studied. Sarcopenia was defined according to the Asian Working Group for Sarcopenia (AWGS) criteria updated in 2019. Diet quality was assessed by using the Chinese Diet Balance Index 2016 (DBI-16), which includes three indicators: the lower bound score (LBS), higher bound score (HBS) and diet quality distance (DQD). Binary logistic regression analysis was used to estimate the risk of sarcopenia associated with diet quality. RESULTS: A total of 49 of the 644 participants were diagnosed with sarcopenia. Excessive intake (score > 0) of cereals, meat, eggs and salt, inadequate intake (score < 0) of vegetables, fruits, dairy products, soybeans and low diet variety were commonly seen in both groups of participants. The participants with sarcopenia had a more serious inadequate intake of fruit than those without sarcopenia (p < 0.05). The overall LBS, HBS and DQD in both groups were in the interval of low-level problems. Compared with participants with a suitable LBS, those with an unsuitable LBS were more likely to have a low gait speed (OR: 2.58; 95%CI: 1.13-7.04) after multiple adjustments. However, the other two DBI-16 indicators, the HBS and DQD, were not associated with sarcopenia or its related diagnostic variables. CONCLUSION: Unfavourable diet quality, mainly referring to inadequate dietary intake in this study, may be a risk factor for low gait speed.

Celecoxib Suppresses NF-κB p65 (RelA) and TNFα Expression Signaling in Glioblastoma.

BACKGROUND: Glioblastoma (GBM) harbors significant genetic heterogeneity, high infiltrative capacity, and patterns of relapse following many therapies. The expression of nuclear factor kappa-B (NF-κB p65 (RelA)) and signaling pathways is constitutively activated in GBM through inflammatory stimulation such as tumor necrosis factor-alpha (TNFα), cell invasion, motility, abnormal physiological stimuli, and inducible chemoresistance. However, the underlying anti-tumor and anti-proliferative mechanisms of NF-κB p65 (RelA) and TNFα are still poorly defined. This study aimed to investigate the expression profiling of NF-κB p65 (RelA) and TNFα as well as the effectiveness of celecoxib along with temozolomide (TMZ) in reducing the growth of the human GBM cell line SF-767. METHODS: genome-wide expression profiling, enrichment analysis, immune infiltration, quantitative expression, and the Microculture Tetrazolium Test (MTT) proliferation assay were performed to appraise the effects of celecoxib and TMZ. RESULTS: demonstrated the upregulation of NF-κB p65 (RelA) and TNFα and celecoxib reduced the viability of the human glioblastoma cell line SF-767, cell proliferation, and NF-κB p65 (RelA) and TNFα expression in a dose-dependent manner. Overall, these findings demonstrate for the first time how celecoxib therapy could mitigate the invasive characteristics of the human GBM cell line SF-767 by inhibiting the NF-κB mediated stimulation of the inflammatory cascade. CONCLUSION: based on current findings, we propose that celecoxib as a drug candidate in combination with temozolomide might dampen the transcriptional and enzymatic activities associated with the aggressiveness of GBM and reduce the expression of GBM-associated NF-κB p65 (RelA) and TNFα inflammatory genes expression.

Molecular Profiling, Characterization and Antimicrobial Efficacy of Silver Nanoparticles Synthesized from Calvatia gigantea and Mycena leaiana against Multidrug-Resistant Pathogens.

The use of natural products isolated from mushrooms against infection, cancer diseases and other oxidative-stress-related diseases is one of the cornerstones of modern medicine. Therefore, we tried to establish a combination of medicinal mushrooms and nanotechnology possibly with the field of medicine for the development of antibacterial agents against these MDR strains. The aim of the research was to understand the molecular identification, characterization and antibacterial action of Calvatia gigantea and Mycena leaiana. The identification of fruiting body species via morpho-anatomical and molecular methods was necessary to analyze the genetic variability and phylogenetic relationships of mushrooms. Phylogenetic analysis revealed that Calvatia from Hunza, Pakistan, exhibited 98% resemblance to the previously discovered Langermannia gigantean (DQ112623) and L. gigantean (LN714562) from northern Europe, and Mycena (Pakistan) showed a 97% similarity to M. leaiana (MF686520) and M. leaiana (MW448623) from the USA. UV-vis, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) were used for AgNPs' characterization. The UV-vis absorption peak of 500-600 nm indicates the AgNPs' presence. XRD results determined Calvatia gigantea AgNPs were nanocrystals and Mycena leaiana seems to be amorphous. In addition, SEM results showed the cubic morphology of C. gigantea with a diameter of 65 nm, and the FTIR spectra of fruiting body revealed the presence of functional groups-carboxyl, nitro, and hydroxyl-in AgNPs, which catalyzed the reduction of Ag+ to Ag0. Further antibacterial activity of mushrooms against MDR strains was determined via agar well diffusion assay, and Minimum Inhibitory Concentration (MIC) was estimated by qualitative experimentation using the broth dilution method. All experiments were conducted in triplicate. The results showed that the mushroom AgNPs, along with their synergy and nano-composites (with the exception of Ethyl-acetate), were shown to have zones of inhibition from 4 mm to 29 mm against multidrug-resistant pathogens such as Acinetobacter baumannii, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, Proteus mirabilis, Enterobacter cloacae and Escherichia coli. The mushroom composites were active against most of the tested microorganisms whilst the lowest MIC value (10-40 mg/mL) was recorded against MDR strains. Hence, the present study suggested the possibility of employing compounds present in mushrooms for the development of new antibacterial agents, as well as efflux pump inhibitors.

Cytotoxic Activity of Phytoconstituents Isolated from Monotheca buxifolia against Hepatocellular Carcinoma Cell Line HepG2: In Vitro and Molecular Docking Studies.

Natural products and conventional chemotherapeutic drugs are believed to enhance anticancer treatment efficacy while lowering toxicity. The current study investigates the cytotoxic and apoptogenic effects of Monotheca buxifolia bioactive compounds on HepG2 cell lines. MTT assay was used to assess the effect on the viability of HepG2 cells. Morphological changes were investigated. Annexin-V-FITC/PI was used to demonstrate apoptotic activity. A molecular dynamics simulation study was carried out to investigate the compound binding pattern in the active site of the PPRAδ protein. MTT and annexin V-FITC/PI assays revealed that the isolated compounds lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate inhibited the growth of hepatocellular cancer cells. The IC50 value for lauric acid was 56.46 ± 1.20 µg/mL, 31.94 ± 1.03 µg/mL for oleanolic acid, and 83.80 ± 2.18 µg/mL for bis(2-ethylhexyl) phthalate. Apoptosis was observed in 29.5, 52.1 and 22.4% of HepG2 cells treated with lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate, respectively, after 24 h of treatment. Morphological assays and Hoechst staining microscopy revealed that the treatment caused morphological changes in the cell membrane and nuclear condensation. The high fluctuation indicates that various interactions were highly potent and widely adopted, and vice versa. Oleanolic acid displayed high residue fluctuation, remaining stable in the active site of the PPRAδ protein and involved in various interactions while remaining locally fluctuating in the binding sites of the other two compounds. These findings concluded that lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate have a significant apoptogenic effect against HepG2 cells in inducing apoptosis. Our findings suggest that these bioactive compounds could be used as adjuvant therapies.

Exploring the Therapeutic Properties of Alga-Based Silver Nanoparticles: Anticancer, Antibacterial, and Free Radical Scavenging Capabilities.

The current study was designed to evaluate the antioxidant, anticancer and antimicrobial activities of silver nanoparticles (AgNPs) biosynthesized by Spirulina platensis extract. The biosynthesized silver nanoparticles were characterized using Fourier transform infrared (FT-IR) analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) analysis. The antioxidant activity of the biosynthesized AgNPs were determined via DPPH radical scavenging assay while its anticancer activity was determined using the MTT assay. The antimicrobial activity of the biosynthesized AgNPs were analyzed by disc diffusion method. Spirulina platensis acts as a reducing and capping agent. The efficacy of silver nanoparticles (AgNPs) in inhibiting the growth of Gram-negative bacteria, specifically Acetobacter, Klebsiella, Proteus vulgaris, and Pseudomonas aeruginosa, was assessed by the utilisation of the diffusion method. The study aimed to evaluate the efficacy of biosynthesized silver nanoparticles (AgNPs) against many strains of Pseudomonas aeruginosa bacteria. The findings of the study revealed that when administered in doses of 50 µl, 75 µl, and 100 µl, the largest observed zone of inhibition corresponded to measurements of 10.5 mm, 14 mm, and 16 mm, respectively. A zone of inhibition with dimensions of 8 mm, 10.5 mm, and 12 mm was detected during testing against Acetobacter at concentrations of 50 µl, 75 µl, and 100 µl, respectively. The findings also indicate that there is a positive correlation between the concentration of AgNP and the DPPH scavenging ability of silver nanoparticles. The percentage of inhibition observed at concentrations of 500 µg/ml, 400 µg/ml, 300 µg/ml, 200 µg/ml, and 100 µg/ml were recorded as 80±1.98, 61±1.98, 52±1.5, 42±1.99, and 36±1.97, respectively. In addition, it was observed that the silver nanoparticles exhibited the greatest antioxidant activity at a concentration of 500 g/ml, with a measured value of 80.89±1.99. The IC-50 values, representing the inhibitory concentration required to achieve 50 % inhibition, were found to be 8.16, 19.15, 30.14, 41.13, and 63.11 at inhibition levels of 36±1.97, 42±1.99, 52±1.5, 61±1.98, and 80±1.98, respectively.

Sustained virological response to antiviral drugs in treatment of different genotypes of HCV cirrhotic patients.

Cirrhosis and liver cancer are both caused by hepatitis C virus (HCV) infection of the liver. Patients with HCV cirrhosis may be treated with one of many antiviral medications, depending on their specific genotype. Samples of cirrhotic HCV were obtained from 190 people at the Khyber Teaching Hospital and the Hayatabad Medical Complex in Peshawar, Pakistan. Multiplex and real-time PCR were used to assess the genotypes and viral loads of the samples, respectively. Sixty patients were given sofosbuvir plus daclatasvir with ribavirin, while the remaining 56 patients were given sofosbuvir with ribavirin for a period of 12-24 weeks. LFTs were also tracked both before and after therapy. Group I (sofosbuvir + daclatasvir) had a sustained virological response of 82.70 percent. Group II (sofosbuvir + daclatasvir with ribavirin) had an 86% sustained virological response, whereas group III (84% sustained virological response) received only ribavirin. When compared to other genotypes, genotype 3 showed the most impressive sustained virologic response (SVR) to the antiviral medicines. Based on the results of this trial, we propose sofosbuvir + daclatasvir ribavirin for the treatment of cirrhotic patients with various HCV genotypes since it produces the greatest sustained virological response.

Phycoremediation of industrial wastewater using Vaucheria debaryana and Cladophora glomerata.

Rapid urbanization and industrialization are regarded as the leading causes of environmental pollution, mainly aquatic pollution. This study was carried out to investigate the use of algal species Cladophora glomerata (CG) and Vaucheria debaryana (VD) as a cost-effective and environmentally friendly phycoremediators for composite industrial effluent. After the pot experimentation using algal species, a considerable decrease in electrical conductivity (EC: 49.10-81.46%), dissolved oxygen (DO: 3.76-8.60%), biological oxygen demand (BOD: 7.81-39.28%), chemical oxygen demand (COD: 7.81-39.28%), total suspended solids (TSS: 38.09-62.21%), and total dissolved solids (TDS: 38.09-62.21%) was observed. Before and after experimentation, the heavy metals were also quantified using atomic absorption spectrophotometry (AAS), and considerable reduction was observed in Cd (41.02-48.75%) and Pb (48.72-57.03%) concentrations. The Cd concentration determined in CTCG (control treatment for Cladophora glomerata containing tap water), CG (treatment pot for Cladophora glomerata containing industrial effluents), CTVD (control pot for Vaucheria debaryana containing tap water), and VD (treatment pot for Vaucheria debaryana containing industrial effluents) biomass was 0.06, 0.499, 0.035, and 0.476 mg/kg, respectively. The Pb uptake determined in CTCG, CG, CTVD, and VD was 0.32, 1.12, 0.31, and 0.49 mg/kg, respectively, using wet digestion method and ASS. The data revealed that C. glomerata has the highest bioconcentration factor for Cd (98.42%), followed by Pb (92.57%) in treatment pots containing industrial effluents (CG and VD). Furthermore, C. glomerata showed the highest bioconcentration factor for Pb (86.49%) as compared to Cd (75%) in tap water (CTCG and CTVD). The t test analysis revealed that heavy metal concentrations significantly (p ≤ 0.05) reduced through the phycoremediation process. The analysis found that C. glomerata removed 48.75% of Cd and 57.027% of Pb from industrial effluents. Phytotoxicity assay was also performed by cultivating Triticum sp. in order to analyze the toxicity of the untreated (control) and treated water samples. Phytotoxicity result shows that the effluent treated with both Cladophora glomerata and Vaucheria debaryana gives better wheat (Triticum sp.) plant % germination, plant height (cm), and root height (cm). The highest plant % germination was showed by treated CTCG (90%), followed by CTVD (80%) and CG (70%) and VD (70%). The study concluded that phycoremediation using C. glomerata and V. debaryana is one of the environment-friendly approaches. The proposed algal-based strategy is economically viable and environmentally sustainable that can be utilized for the remediation of industrial effluents.

Modelling Electricity Consumption During the COVID19 Pandemic: Datasets, Models, Results and a Research Agenda.

The COVID19 pandemic has impacted the global economy, social activities, and Electricity Consumption (EC), affecting the performance of historical data-based Electricity Load Forecasting (ELF) algorithms. This study thoroughly analyses the pandemic's impact on these models and develop a hybrid model with better prediction accuracy using COVID19 data. Existing datasets are reviewed, and their limited generalization potential for the COVID19 period is highlighted. A dataset of 96 residential customers, comprising 36 and six months before and after the pandemic, is collected, posing significant challenges for current models. The proposed model employs convolutional layers for feature extraction, gated recurrent nets for temporal feature learning, and a self-attention module for feature selection, leading to better generalization for predicting EC patterns. Our proposed model outperforms existing models, as demonstrated by a detailed ablation study using our dataset. For instance, it achieves an average reduction of 0.56% & 3.46% in MSE, 1.5% & 5.07% in RMSE, and 11.81% & 13.19% in MAPE over the pre- and post-pandemic data, respectively. However, further research is required to address the varied nature of the data. These findings have significant implications for improving ELF algorithms during pandemics and other significant events that disrupt historical data patterns.

Circulating miRNA-192 and miR-29a as Disease Progression Biomarkers in Hepatitis C Patients with a Prevalence of HCV Genotype 3.

MicroRNAs miR-29a and miR-192 are involved in inflammatory and fibrotic processes of chronic liver disease, and circulating miR-29a is suggested to diagnose fibrosis progression due to hepatitis C virus (HCV) infection. This study aimed to evaluate the expression profile of circulating miR-192 and 29a in a patient cohort with a high frequency of HCV genotype-3. A total of 222 HCV blood samples were collected and serum were separated. Patients were classified into mild, moderate, and severe liver injury based on their Child-Turcotte-Pugh CTP score. RNA was isolated from the serum and used for quantitative real-time PCR. The HCV genotype-3 (62%) was the predominant HCV genotype. In HCV patients, the serum miR-192 and miR-29a levels were significantly upregulated in comparison to healthy controls (p = 0.0017 and p = 0.0001, respectively). The progression rate of miR-192 and 29a in the patient group with mild was highly upregulated compared to patients with moderate and severe hepatitis infection. The ROC curve of miR-192 and miR-29a of moderate liver disease had a significant diagnostic performance compared to the other HCV-infected groups. The increase in miR-29a and miR-192 serum levels was even slightly higher in patients with HCV genotype-3 than in non-genotype-3 patients. In conclusion, serum miR-192 and miR-29a levels significantly increased during the progression of chronic HCV infection. The marked upregulation in patients with HCV genotype-3 suggests them as potential biomarkers for hepatic disease, independently of the HCV genotype.