Lamiales epidermal dynamics: Unveiling antimicrobial resilience in a structural symphony.

This research on Lamiales epidermal anatomy not only provides in-depth understanding of their structural traits but also highlights the significance of uncovering the inherent antimicrobial resilience embedded within these plants. Such insights hold promise for advancing natural product-based approaches in medicine, potentially contributing to the development of novel antimicrobial agents inspired by Lamiales unique biological defense mechanisms. Scanning microscopic tools were utilized to conduct foliar epidermal anatomy of nine species that belong to seven genera and four families within the Lamiales order, Plantaginaceae, Scrophulariaceae, Verbenaceae, and Lamiaceae. This approach aimed to gather both qualitative and quantitative data, facilitating the assessment of taxonomic microanatomical significance. The shape of epidermal cells and their anticlinal walls; number of epidermal cells, stomata, and trichomes; type of stomata and trichomes; length and width of epidermal cells, trichomes, stomatal pore, guard cells, and subsidiary cells; and stomatal index were determined statistically. Most of the species examined were amphistomatous and showed extensive array of trichomes diversity. The exploration of Lamiales epidermal micromorphology and their antimicrobial potential were significant for their implications in multidisciplinary fields. The pharmacological research to utilize sustainable agricultural practices prompts avenues to strengths of Lamiales order for the development of novel antimicrobial solutions and ecological benefits. RESEARCH HIGHLIGHTS: Diverse trichome morphometry reveals a wide array of trichome structures across Lamiales species. Epidermal microscopic architecture variability of epidermal cell shapes and sizes signifies the interspecies variability. Secondary metabolite localization within microanatomical structures elucidates potential hotspots for antimicrobial compound production.

Biological and molecular characterization of citrus bent leaf viroid.

Background and aim: Citrus bent leaf viroid (CBLVd) is one of the emerging and widely distributed viroids in citrus-growing areas of the world, including Pakistan. Previously, CBLVd has been reported in Pakistan for the first time in 2009. Therefore, characterization of CBLVd is required to monitor the viroid status in the citrus orchards concerning citrus decline. Methods: Biological and molecular characterization of CBLVd was studied through biological indexing and confirmation through RT-PCR, followed by phylogenetic analysis of selected CBLVd isolates. Among four citrus cultivars viz., Kinnow (Citrus nobilis × Citrus deliciosa), Mosambi (C. sinensis), Futrell's Early (C. reticulata) and Lemon (C. medica) used as indicator plants for two transmission trials viz., graft inoculation and mechanical inoculation. Graft inoculation was more efficient than mechanical inoculation. Results: Symptoms such as mild mosaic, slight backward leaf bending, and leaf curling were observed after eight months' post-inoculation. Citrus nobilis × Citrus deliciosa, C. reticulata and C. sinensis were more sensitive to CBLVd as compared to C. medica. Inoculated plants were reconfirmed through RT-PCR amplicons of 233 bp. The phylogenetic tree of submitted sequences showed more than 90% relevance of CBLVd in Pakistan compared to the rest of the world. Conclusions: There was slight genetic variability, but more than 90% relevance was found among the submitted and already reported CBLVd isolate from Pakistan. Scanty literature is available regarding the biological and molecular studies of CBLVd in Pakistan. Therefore, the transmission and molecular characterization of CBLVd in Pakistan were studied for the first time.

Chemical Composition, Antioxidant, Anticancer, and Antibacterial Activities of Roots and Seeds of Ammi visnaga L. Methanol Extract.

For centuries, plants and their components have been harnessed for therapeutic purposes, with Ammi visnaga L. (Khella) being no exception to this rich tradition. While existing studies have shed light on the cytotoxic and antimicrobial properties of seed extracts, there remains a noticeable gap in research about the antimicrobial, antioxidant, and anticancer potential of root extracts. This study seeks to address this gap by systematically examining methanol extracts derived from the roots of A. visnaga L. and comparing their effects with those of seed extracts specifically against breast cancer cells. Notably, absent from previous investigations, this study focuses on the comparative analysis of the antimicrobial, antioxidant, and anticancer activities of both root and seed extracts. The methanol extract obtained from A. visnaga L. seeds demonstrated a notably higher level of total phenolic content (TPC) than its root counterpart, measuring 366.57 ± 2.86 and 270.78 ± 2.86 mg GAE/g dry weight of the dry extract, respectively. In the evaluation of antioxidant activities using the DPPH method, the IC50 values for root and seed extracts were determined to be 193.46 ± 17.13 µg/mL and 227.19 ± 1.48 µg/mL, respectively. Turning our attention to cytotoxicity against breast cancer cells (MCF-7 and MDA-MB-231), both root and seed extracts displayed similar cytotoxic activities, with IC50 values of 92.45 ± 2.14 µg/mL and 75.43 ± 2.32 µg/mL, respectively. Furthermore, both root and seed extracts exhibited a noteworthy modulation of gene expression, upregulating the expression of caspase and Bax mRNA levels while concurrently suppressing the expression of anti-apoptotic genes (Bcl-xL and Bcl-2), thereby reinforcing their potential as anticancer agents. A. visnaga L. seed extract outperforms the root extract in antimicrobial activities, exhibiting lower minimum inhibitory concentrations (MICs) of 3.81 ± 0.24 to 125 ± 7.63 µg/mL. This highlights the seeds' potential as potent antibacterial agents, expanding their role in disease prevention. Overall, this study underscores the diverse therapeutic potentials of A. visnaga L. roots and seeds, contributing to the understanding of plant-derived extracts in mitigating disease risks.

Comparative taxonomical, biological and pharmacological potential of healthy and geminivirus infected leaves of Hibiscus rosa-sinensis L.: First report.

In the present research project, the first report on comparative analysis of the taxonomical, biological and pharmacological potential of healthy and geminivirus infected Hibiscus rosa sinensis (L.) leaves of the family Malvaceae was done by using different micro and macroscopic techniques. First of all, leaves were characterized for Cotton leaf curl Multan virus (CLCuMuV) and its associated betasatellite (Cotton leaf curl Multan Betasatellite; CLCuMB). Different morphological parameters like shape and size of stem, leaves, seeds and roots, presence and absence of ligule, distance between nodes and internodes and type of inflorescence etc. were analyzed. CLCuMuV infected H. rosa-sinensis revealed systematic symptoms of infection like chlorosis of leaves, stunted growth, decrease in size of roots, shoots and distortion etc. Anatomical investigation was performed under light ad scanning electron microscope. Different anatomical features like length and shape of guard cells, subsidiary cells, presence or absence of stomata, secretory ducts and trichomes were examined. In both plant samples anomocytic types of stomata and elongated, non-glandular and pointed tip trichomes were present, but the size (especially length and width) of trichomes and other cells like epidermal, subsidiary, and guard cells were highest in virus infected plants likened to healthy one. In the antibacterial activity, the maximum antibacterial potentail was seen in methanolic extract of K. pneumonea while antifungal activity was shown by methanolic extract of A. solani. Plants interact with different biological entities according to environmental conditions continuously and evolved. These types of interactions induce changes positively and negatively on plant metabolism and metabolites production. Many plant viruses also attacked various host plants consequently alter their secondary metabolism. To overcome such virus infected plants produces many important and different types of secondary plant metabolites as a defense response. Subsequent analysis of this n-hexane plant extract using Gas chromatography mass spectroscopy technique revealed that Hibiscus eluted contained 10 main compounds in Healthy sample and 13 compounds in infected one. Presence of essential secondary metabolites were also analyzed by FTIR analysis. The present study provides a comprehensive and novel review on taxonomy (morphology, anatomy) and antimicrobial potential of both healthy and geminivirus infected H. rosa-sinensis.

AI-driven Discovery of Celecoxib and Dexamethasone for Exploring their Mode of Action as Human Interleukin (IL-6) Inhibitors to Treat COVID-19-induced Cytokine Storm in Humans.

BACKGROUND: In the case of COVID-19 patients, it has been observed that the immune system of the infected person exhibits an extreme inflammatory response known as cytokine release syndrome (CRS) where the inflammatory cytokines are swiftly produced in quite large amounts in response to infective stimuli. Numerous case studies of COVID-19 patients with severe symptoms have documented the presence of higher plasma concentrations of human interleukin-6 (IL-6), which suggests that IL-6 is a crucial factor in the pathophysiology of the disease. In order to prevent CRS in COVID-19 patients, the drugs that can exhibit binding interactions with IL-6 and block the signaling pathways to decrease the IL-6 activity may be repurposed. METHODS: This research work focused on molecular docking-based screening of the drugs celecoxib (CXB) and dexamethasone (DME) to explore their potential to interact with the binding sites of IL-6 protein and reduce the hyper-activation of IL-6 in the infected personnel. RESULTS: Both of the drugs were observed to bind with the IL-6 (IL-6 receptor alpha chain) and IL-6Rα receptor with the respective affinities of -7.3 kcal/mol and -6.3 kcal/mol, respectively, for CXB and DME. Moreover, various types of binding interactions of the drugs with the target proteins were also observed in the docking studies. The dynamic behaviors of IL-6/IL-6Rα in complex with the drugs were also explored through molecular dynamics simulation analysis. The results indicated significant stabilities of the acquired drug-protein complexes up to 100 ns. CONCLUSION: The findings of this study have suggested the potential of the drugs studied to be utilized as antagonists for countering CRS in COVID-19 ailment. This study presents the studied drugs as promising candidates both for the clinical and pre-clinical treatment of COVID-19.

Antimicrobial and antioxidant potential of the silver nanoparticles synthesized using aqueous extracts of coconut meat (Cocos nucifera L).

Human pathogenic fungi and bacteria pose a huge threat to human life, accounting for high rates of mortality every year. Unfortunately, the past few years have seen an upsurge in multidrug resistance pathogens. Consequently, finding an effective alternative antimicrobial agent is of utmost importance. Hence, this study aimed to phytofabricate silver nanoparticles (AgNPs) using aqueous extracts of the solid endosperm of Cocos nucifera L, also known as coconut meat (Cm). Green synthesis is a facile, cost-effective and eco-friendly methods which has several benefits over other physical and chemical methods. The synthesized nanoparticles were characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The Cm-AgNPs showed a UV-Vis peak at 435 nm and were crystalline and quasi-spherical, with an average size of 15 nm. The FTIR spectrum displayed functional groups of phenols, alkaloids, sugars, amines, and carbonyl compounds, which are vital in the reduction and capping of NPs. The antibacterial and anticandidal efficacy of the Cm-AgNPs was assessed by the agar-well diffusion method and expressed as a zone of inhibition (ZOI). Amongst all the test isolates, Staphylococcus epidermidis, Candida auris, and methicillin-resistant Staphylococcus epidermidis were more susceptible to the NPs with a ZOI of 26.33 ± 0.57 mm, 19.33 ± 0.57 mm, and 18 ± 0.76 mm. The MIC and MFC values for Candida spp. were higher than the bacterial test isolates. Scanning electron microscopic studies of all the test isolates at their MIC concentrations showed drastically altered cell morphology, indicating that the NPs could successfully cross the cell barrier and damage the cell integrity, causing cell death. This study reports the efficacy of Cm-AgNPs against several Candida and bacterial strains, which had not been reported in earlier studies. Furthermore, the synthesized AgNPs exhibited significant antioxidant activity. Thus, the findings of this study strongly imply that the Cm-AgNPs can serve as promising candidates for therapeutic applications, especially against multidrug-resistant isolates of Candida and bacteria. However, further investigation is needed to understand the mode of action and biosafety.

Prospect of herbal medication as prevention against COVID variants.

Personal immunity frolicked an essential role in combating COVID-19 impacts on human health individually and collectively in community. Literature represented the fact about food or nutritional supplements are certified to protect against diseases; this was the reason behind public trust on certain plants and other commercial products to boost up immunity against coronavirus disease. Present study was conducted to observe the attitude of common public towards natural herbs in treating various diseases and to assess the possible potential of herbal medication in prevention of negative impacts of different variants of COVID-19 on human health at herbal clinic named "Pakistan Matab". Results concluded that most of the patients (About 80%) avoided COVID-19 testing even on experiencing major symptoms and they preferred herbal medication. Patients who died by COVID-19 were also experiencing different diseases like liver and Kideny malfunctioning; old age was another significant factor in this case. About 90% of patients were COVID symptomatic and 10% were carrying other diseases during observational study period at herbal clinic. Study represented that patients who visited clinic, have a faith on herbal medication with about 60% of patients in favor of vaccine and allopathic medication in combination with herbal treatment. Study investigated that vaccine was only for one type of variant and use of herbal medicines could be better option to boost up immunity against various COVID variants.

Determinants, predictors and negative impacts of burnout among health care workers during COVID-19 pandemic.

The first defense line of the battle, healthcare workers (HCWs), faces a significant challenge in managing the current COVID-19 pandemic. An online electronic survey was sent to HCWs via email and social media networks. Socio-demographic data and work environment-related variables were assessed. Consequences of burnout (BO) were reported, e.g., elicited medical errors. Maslach burnout inventory was used to diagnose BO. Two hundred and eighty-four participants were included with a mean age of 39.83 ± 7.34 years, 70.8% worked in the COVID-19 frontline, 91.9% were followed daily updates about COVID-19, 63.7% were not satisfied with the coordination between triage and isolation, 64.4% got COVID-19 infection, 91.9% had a colleague or family member developed COVID-19 infection, and 21.5% experienced a colleague /a family member died due to COVID-19. Multivariate analysis by linear regression revealed that; working as a frontline HCW (OR 1.28, CI = 0.14-2.55) and sleep deprivation (OR 3.93, CI = 1.88-8.22) were the predictors of burnout.

Masitinib analogues with the N-methylpiperazine group replaced - A new hope for the development of anti-COVID-19 drugs.

Masitinib is an orally acceptable tyrosine kinase inhibitor that is currently investigated under clinical trials against cancer, asthma, Alzheimer's disease, multiple sclerosis and amyotrophic lateral sclerosis. A recent study confirmed the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity of masitinib through inhibition of the main protease (Mpro) enzyme, an important pharmacological drug target to block the replication of the coronavirus. However, due to the adverse effects and lower potency of the drug, there are opportunities to design better analogues of masitinib. Herein, we substituted the N-methylpiperazine group of Masitinib with different chemical moieties and evaluated their drug-likeness and toxicities. The filtered analogues were subjected to molecular docking studies which revealed that the analogues with substituents methylamine in M10 (CID10409602), morpholine in M23 (CID59789397) and 4-methylmorpholine in M32 (CID143003625) have a stronger affinity to the drug receptor compared to masitinib. The molecular dynamics (MD) simulation analysis reveals that the identified analogues alter the mobility, structural compactness, accessibility to solvent molecules, and the number of hydrogen bonds in the native target enzyme. These structural alterations can help explain the inhibitory mechanisms of these analogues against the target enzyme. Thus, our studies provide avenues for the design of new masitinib analogues as the SARS-CoV-2 Mpro inhibitors.

Vaccine Acceptance and Hesitancy among Hospitalized COVID-19 Patients in Punjab, Pakistan.

Vaccine hesitancy is widespread in many parts of the globe, particularly in low-middle-income countries. Therefore, we surveyed a sample of hospitalized COVID-19 patients to assess COVID-19 vaccine acceptance and vaccine hesitancy in a low-middle-income country. A cross-sectional sample of 385 confirmed reverse transcriptase-polymerase chain reaction COVID-19 patients treated at secondary and tertiary care hospitals in Punjab, Pakistan, were analyzed to assess COVID-19 vaccine uptake and vaccine hesitancy. The construct validity and reliability of the 11-item vaccine hesitancy questionnaire were also examined. In addition, multivariate logistic regression was used. The majority of the COVID-19 patients admitted to hospitals were not vaccinated (84%). Of those who were willing to receive vaccination, the majority (55%) considered vaccines an effective way to protect people from COVID-19. However, those who were not willing to receive their COVID-19 vaccine had significantly higher hesitancy than those willing to receive their COVID-19 vaccine. In addition, older hospitalized COVID-19 patients aged 60 years or above (20-29 years: OR 0.10; 95% CI 0.01-0.72, p = 0.001) and patients from urban areas (OR 3.16 95% CI 1.27-7.87, p = 0.013) were more likely to receive the COVID-19 vaccine than younger patients and patients from rural areas. Patients with no formal education had significantly higher hesitancy (OR 5.26; 96% CI 1.85-14.97, p = 0.002) than participants with graduation and above education. More than half of the study's participants did not trust information shared on social media about COVID-19 vaccines and cited newspapers/news channels as their main source of information. The study provides important insights into COVID-19 vaccine acceptance and the impact of vaccination campaigns. Many unvaccinated COVID-19 patients in hospitals highlight the need for an effective vaccination drive to protect people from acquiring infection and subsequent hospitalization.

Novel findings in context of molecular diversity and abundance of bacteriophages in wastewater environments of Riyadh, Saudi Arabia.

The diversity among bacteriophages depends on different factors like ecology, temperature conditions and genetic pool. Current study focused on isolation, identification and diversity of phages from 34 sewage water samples collected from two different wastewater treatment plants (WWTPs), King Saud University wastewater treatment plants (KSU-WWTP) and Manfoha wastewater treatment plants (MN-WWTP) in Riyadh, Saudi Arabia. Samples were analyzed by PCR and Next Generation Sequencing (NGS). Siphoviridae, Podoviridae and Myoviridae families were detected by family-specific PCR and highest prevalence of Myoviridae 29.40% was found at MN-WWTP followed by 11.76% at KSU-WWTP. Siphoviridae was detected 11.76% at MN-WWTP and 5.88% at KSU-WWTP. Lowest prevalence for Podoviridae family (5.88%) was recorded at MN-WWTP. Significant influence of temporal variations on prevalence of Myoviridae and Siphoviridae was detected in both WWTP and MN-WWTP, respectively. Highest phage prevalence was obtained in August (75%), followed by September (50%). Highest phage prevalence was recorded at a temperature range of 29-33°C. Significant influence of temperature on the prevalence of Myoviridae phages was detected at MN-WWTP. Four bacteriophages with various abundance levels were identified by NGS. Cronobacter virus Esp2949-1 was found first time with highest abundance (4.41%) in wastewater of Riyadh. Bordetella virus BPP1 (4.14%), Dickeya virus Limestone (1.55%) and Ralstonia virus RSA1 (1.04%) were also detected from samples of MN-WWTP. Highest occurrence of Bordetella virus BPP1 (67%) and (33.33%) was recorded at KSU-WWTP and MN-WWTP, respectively. Highest Bordetella virus BPP1 occurrence was recorded in September (50%) followed by August (40%). The findings of study showed new insights of phage diversity from wastewater sources and further large-scale data studies are suggested for comprehensive understanding.

Potential of antiviral peptide-based SARS-CoV-2 inactivators to combat COVID-19.

The appearance of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lack of effective antiviral therapeutics for coronavirus disease 2019 (COVID-19), a highly infectious disease caused by the virus, demands the search for alternative therapies. Most antiviral drugs known are passive defenders which must enter the cell to execute their function and suffer from concerns such as permeability and effectiveness, therefore in this current study, we aim to identify peptide inactivators that can act without entering the cells. SARS-CoV-2 spike protein is an essential protein that plays a major role in binding to the host receptor angiotensin-converting enzyme 2 and mediates the viral cell membrane fusion process. SARS vaccines and treatments have also been developed with the spike protein as a target. The virtual screening experiment revealed antiviral peptides which were found to be non-allergen, non-toxic and possess good water solubility. U-1, GST-removed-HR2 and HR2-18 exhibit binding energies of -47.8 kcal/mol, -43.01 kcal/mol, and -40.46 kcal/mol, respectively. The complexes between these peptides and spike protein were stabilized through hydrogen bonds as well as hydrophobic interactions. The stability of the top-ranked peptide with the drug-receptor is evidenced by 50-ns molecular dynamics (MD) simulations. The binding of U-1 induces conformational changes in the spike protein with alterations in its geometric properties such as increased flexibility, decreased compactness, the increased surface area exposed to solvent molecules, and an increase in the number of total hydrogen bonds leading to its probable inactivation. Thus, the identified antiviral peptides can be used as anti-SARS-CoV-2 candidates, inactivating the virus's spike proteins and preventing it from infecting host cells.

Exploring the phytochemicals of Platycodon grandiflorus for TMPRSS2 inhibition in the search for SARS-CoV-2 entry inhibitors.

Platycodon grandiflorus (Jacq.) A. DC. (Campanulaceae) is commonly known as a balloon flower whose rhizomes have been widely utilized in traditional Chinese medicine (TCM) and in various Japanese prescriptions for the treatment of respiratory diseases, diabetes, and inflammatory disorders. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) global pandemic requires priming of the virus's spike (S) protein by cleavage of the S proteins by a multi-domain type II transmembrane serine protease, transmembrane protease serine 2 (TMPRSS2) to gain entry into the host cell. The current research aims at the screening of active phytocompounds of P. grandiflorus as potential inhibitors of cellular TMPRSS2 using molecular docking and molecular dynamics simulations approach. In silico toxicity analyses show that out of a total of 34 phytocompounds selected for the study, 12 compounds obey Lipinski's rule of five and have favourable pharmacokinetic properties. The top three lead molecules identified here were Apigenin, Luteolin and Ferulic acid which exhibited binding energies of -7.47 kcal/mol, -6.8 kcal/mol and -6.62 kcal/mol respectively with corresponding inhibition constants of 3.33 µM, 10.39 µM and 13.95 µM. The complexes between the lead molecules and the receptor were held by hydrogen bond interactions with key residues such as Gly383, Gly385, Glu389, Lys390, Asp435, Ser436, Ser441, Cys465 and Lys467, and hydrophobic interactions with surrounding residues. The stability of the protein-ligand complexes was evaluated during 100 ns molecular dynamics (MD) simulation by analysing key geometric properties such as RMSD, RMSF, radius of gyration, total solvent accessible surface area and the number of hydrogen bonds. The binding free energies analysis using MD simulations revealed that the compounds and TMPRSS2 have favourable thermodynamic interactions, which are primarily driven by van der Waals forces. As a result, the selected bioactive phytochemicals from P. grandiflorus that target the cellular TMPRSS2 could offer an alternative treatment option against SARS-CoV-2 infections.

The Prospective Effect of Allopurinol on the Oxidative Stress Index and Endothelial Dysfunction in Covid-19.

SARS-CoV-2 by the direct cytopathic effect or indirectly through the propagation of pro-inflammatory cytokines could cause endothelial dysfunction (ED) and oxidative stress (OS). It has been reported that OS is triggered by various types of viral infections, including SARS-CoV-2. Into the bargain, allopurinol is regarded as a potent antioxidant that acts through inhibition of xanthine oxidase (XO), which is an essential enzyme of purine metabolism. Herein, the present study aimed to find the potential protective effects of allopurinol on the biomarkers of OS and ED in patients with severe Covid-19. This single-center cohort study recruited 39 patients with mild-moderate Covid-19 compared with 41 patients with severe Covid-19. Nineteen patients with severe Covid-19 were on the allopurinol treatment because of underlying chronic gout 3 years ago compared with 22 Covid-19 patients not on this treatment. The recruited patients were allocated into three groups: group I, mild-moderate Covid-19 on the standard therapy (n = 39); group II, severe Covid-19 patients on the standard therapy only (n = 22); and group III, severe Covid-19 patients on the standard therapy plus allopurinol (n = 19). The duration of the study was 3 weeks from the time of hospitalization till the time of recovery. In addition, inflammatory biomarkers (D-dimer, LDH, ferritin, CRP, procalcitonin), neutrophil-lymphocyte ratio (NLR), endothelin-1 (ET-1), uric acid and oxidative stress index (OSI), CT scan score, and clinical score were evaluated at the time of admission and discharge regarding the effect of allopurinol treatment adds to the standard treatment of Covid-19. Allopurinol plus standard treatment reduced LDH, ferritin, CRP, procalcitonin, and ET-1 serum level significantly (P < 0.05) compared with Covid-19 patients on standard treatment. Besides, neutrophil (%), lymphocyte (%), and neutrophil-lymphocyte ratio (NLR) were reduced in patients with severe Covid-19 on standard treatment plus allopurinol compared with Covid-19 patients on standard treatment alone (P < 0.01). OSI was higher in patients with severe Covid-19 than mild-moderate Covid-19 patients (P = 0.00001) at admission. At the time of discharge, the oxidative status of Covid-19 patients was significantly improved compared with that at admission (P = 0.01). In conclusion, Covid-19 severity is linked with high OS and inflammatory reaction with ED development. High uric acid in patients with severe Covid-19 is correlated with high OS and inflammatory biomarkers. Allopurinol with standard treatment in patients with severe Covid-19 reduced oxidative and inflammatory disorders with significant amelioration of ED and clinical outcomes.

Occurrence of extended-spectrum ß-lactamase, AmpC, and carbapenemase-producing genes in gram-negative bacterial isolates from human immunodeficiency virus infected patients.

BACKGROUND: Progressive decline of immune response in HIV patients makes them susceptible to frequent bacterial infections. High usage of antibiotics influences the emergence of multidrug-resistant bacteria and worsens the clinical outcomes. In this study, the occurrence of drug-resistant genes in Gram-negative bacterial isolates from HIV patients in South India was analyzed. METHODS: A total of 173 Gram-negative bacterial (GNB) isolates from HIV patients were screened for antibiotic susceptibility profile using the Kirby-Bauer diskdiffusion method. Positivity of drug-resistant genes was analyzed using polymerase chain reaction method. RESULTS: In this study, 72.8% of bacterial isolates were obtained from urine specimens, and Escherichia coli (47.4%) was the predominantly isolated bacterium. Overall, 87.3% and 83.2% of GNB were resistant to 3rd generation cephalosporin antibiotics such as cefotaxime and ceftazidime, respectively, 56.6% were resistant to cephamycin (cefoxitin) and 43% to carbapenem (imipenem) antibiotics. Extended-spectrum ß-lactamases (ESBL) production was noted among 79.5% of GNB isolates, followed by AmpC (57.1%) and Metallo ß-lactamases (37.3%). Molecular analysis revealed that ESBL genes such as blaTEM (94.1%), blaCTX-M (89.2%), and blaSHV (24.2%) were detected at higher levels among GNB isolates. Carbapenemase-producing genes such as blaOXA-48 (20%), blaOXA-23 (2.6%), and both blaOXA-23 and blaOXA-51 like genes (2.6%) and AmpC producing genes such as blaCIT (26.7%), blaDHA (3.6%), and blaACC (1.8%) were detected at low-level. CONCLUSIONS: This study concludes that ESBL producing genes are detected at high level among gram-negative bacterial isolates from HIV patients in South India.

Gum mediated synthesis and characterization of CuO nanoparticles towards infectious disease-causing antimicrobial resistance microbial pathogens.

BACKGROUND: In this work biologically active CuO nanoparticle were discussed. The literature suggests that CuO shows very good antibacterial activity on both Gram positive and Gram-negative bacterial strains. Further, it is used in antibacterial coatings on various substrates to prevent various kinds of medical equipment's. Here CuO NPs was prepared via greener approach and almond gum is used as a reducing agent. Almond gum is nontoxic and contains huge amount of polysaccharides. Hence, the gum mediated CuO NPs can be used to treat urinary tract infection (UTI). METHOD: The CuO NPs were characterized using UV, FTIR, XRD and HESEM with EDX analysis. The antibacterial (both Gram positive and Gram negative) effects of CuO NPs were determined with agar well diffusion method. RESULTS: The CuO NPs were characterized by X-ray diffraction pattern result indicates that the monoclinic structure with average crystallite size about 12.91 nm. Straight line model in Scherrer method results found to be crystallite size. The crystallite size and microstrain were estimated in W-H analysis. Lorentz polarization factor, size-strain plot (SSP), morphological index (M-I) and dislocation density were calculated based on x-ray diffraction data. The FTIR analysis confirms presence of Cu and O band. From the absorption spectrum of CuO NPs, it was found to be cutoff wavelength of 230 nm and direct bandgap was found to be 4.97 eV. Morphology analysis shows that the synthesized of CuO NPs reveals agglomerated and spherical in shape. It was found to be 16 nm-25 nm. Energy dispersive spectroscopy (EDX) result indicates percentages of Cu and O element present in the sample. Antimicrobial studies reveal zone of inhibition of CuO NPs. This was used in different pathogens such as gram-positive and Gram-negative bacteria. This study shows exhibit excellent antimicrobial effects of CuO NPs. CONCLUSION: Hence, in this article the novel and cost-effective method to prepare CuO NPs was discussed. The prepared CuO NPs can be used as an antifungal and antibacterial reagent.

The Antimicrobial Activities of Silver Nanoparticles from Aqueous Extract of Grape Seeds against Pathogenic Bacteria and Fungi.

Grape seed extract (GSE) is a natural source of polyphenolic compounds and secondary metabolites, which have been tested for their possible antimicrobial activities. In the current study, we tested the antibacterial and antifungal activities of aqueous GSE and the biosynthesized silver nanoparticles loaded with GSE (GSE-AgNPs) against different pathogens. The biosynthesized GSE-AgNPs were assessed by UV spectroscopy, dynamic light scattering (DLS), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and gas chromatography/mass spectrometry (GC/MS). The antimicrobial activities were assessed against different bacterial and fungal species. DLS analysis showed that GSE-AgNPs had a Z-Average of 91.89 nm while UV spectroscopy showed that GSE-AgNPs had the highest absorbance at a wavelength of ~415 nm. FTIR analysis revealed that both of GSE and GSE-AgNPs consisted of different functional groups, such as hydroxyl, alkenes, alkyne, and aromatic rings. Both FE-SEM and TEM showed that GSE-AgNPs had larger sizes and rough surfaces than GSE and AgNO3. The results showed significant antimicrobial activities of GSE-AgNPs against all tested species, unlike GSE, which had weaker and limited effects. More studies are needed to investigate the other antimicrobial activities of GSE.

Opportunistic mycoses in COVID-19 patients/survivors: Epidemic inside a pandemic.

Being considered minor vexations, fungal infections hinder the life of about 15% of the world population superficially, with rare threats to life in case of invasive sepsis. A significant rise in the intrusive mycoses due to machiavellian fungal species is observed over the years due to increased pathology and fatality in people battling life-threatening diseases. Individuals undergoing therapy with immune suppressive drugs plus recovering from viral infections have shown to develop fungal sepsis as secondary infections while recovering or after. Currently, the whole world is fighting against the fright of Coronavirus disease (COVID-19), and corticosteroids being the primitive therapeutic to combat the COVID-19 inflammation, leads to an immune-compromised state, thereby allowing the not so harmful fungi to violate the immune barrier and flourish in the host. A wide range of fungal co-infection is observed in the survivors and patients of COVID-19. Fungal species of Candida, Aspergillus and Mucorales, are burdening the lives of COVID-19 patients/survivors in the form of Yellow/Green, White and Black fungus. This is the first article of its kind to assemble note on fungal infections seen in the current human health scenario till date and provides a strong message to the clinicians, researchers and physicians around the world "non-pathological fungus should not be dismissed as contaminants, they can quell immunocompromised hosts".

In-vitro antimicrobial susceptibility pattern of lipopeptide against drug resistant Vibrio species.

BACKGROUND: The unrestricted application of antibiotics increased antimicrobial resistance in bacteria through horizontal gene transfer of resistant genes from the pathogenic sources and the evolution of multi-drug resistance organisms. The application of antibiotics caused severe risk to human health because animals may transmit diseases to humans. Hence, the search of novel antimicrobial agents from microbial sources is an urgent need. METHODS: A lipopeptide producing stain SU05 was isolated from the pond water by serial dilution method. The lipopeptide yield was improved after optimization method and the yield was analyzed using High Performance Liquid chromatography. The influence of wheat bran (0.5%-2.5%) and rice bran (0.5%-2.5%), pH (5.5-8.5), temperature (25-40 °C) were screened to improve the production of lipopeptides by stain SU05 in submerged fermentation. Antibacterial activity of crude lipopeptide was tested against Vibrio anguillarum, Vibrio harveyi, Vibrio vulnificus, Vibrio salmonicida, Vibrio septicus, Vibrio fischeri, and Vibrio splendidus. The influence of lipopeptide on enzymes and antimicrobial property was analyzed. RESULTS: Lipopeptide production was improved after nutrient supplements and optimization of physical factors. Lipopeptide showed potent activity against multi-drug resistant bacterial strains such as, V. anguillarum, V. harveyi, V. vulnificus, V. salmonicida, V. septicus, V. fischeri, and V. splendidus. Lipopeptide shows stability on various enzymes and this clearly revealed that the purified lipopeptide was highly stable in the presence of proteolytic enzymes. The findings suggest that lipopeptide SU05 characterized from the bacteria can survive at acidic environment in the intestine, and could be used to formulate fish feed. CONCLUSIONS: The finding showed that the characterized lipopepties synthesized by B. amyloliquefaciens SU05 had a broad spectrum antibiotic potential against multidrug resistant Vibriosis causing bacterial pathogens. They were highly stable at broad temperature and pH ranges. These results demonstrated stability of lipopeptide at extreme conditions. The stability and activity of lipopeptide at extreme climatic condition is also useful for the application in pharmaceutical and food processing industries.

Role of Persistent Organic Pollutants in Breast Cancer Progression and Identification of Estrogen Receptor Alpha Inhibitors Using In-Silico Mining and Drug-Drug Interaction Network Approaches.

The strong association between POPs and breast cancer in humans has been suggested in various epidemiological studies. However, the interaction of POPs with the ERα protein of breast cancer, and identification of natural and synthetic compounds to inhibit this interaction, is mysterious yet. Consequently, the present study aimed to explore the interaction between POPs and ERα using the molecular operating environment (MOE) tool and to identify natural and synthetic compounds to inhibit this association through a cluster-based approach. To validate whether our approach could distinguish between active and inactive compounds, a virtual screen (VS) was performed using actives (627 compounds) as positive control and decoys (20,818 compounds) as a negative dataset obtained from DUD-E. Comparatively, short-chain chlorinated paraffins (SCCPs), hexabromocyclododecane (HBCD), and perfluorooctanesulfonyl fluoride (PFOSF) depicted strong interactions with the ERα protein based on the lowest-scoring values of -31.946, -18.916, -17.581 kcal/mol, respectively. Out of 7856 retrieved natural and synthetic compounds, sixty were selected on modularity bases and subsequently docked with ERα. Based on the lowest-scoring values, ZINC08441573, ZINC00664754, ZINC00702695, ZINC00627464, and ZINC08440501 (synthetic compounds), and capsaicin, flavopiridol tectorgenin, and ellagic acid (natural compounds) showed incredible interactions with the active sites of ERα, even more convening and resilient than standard breast cancer drugs Tamoxifen, Arimidex and Letrozole. Our findings confirm the role of POPs in breast cancer progression and suggest that natural and synthetic compounds with high binding affinity could be more efficient and appropriate candidates to treat breast cancer after validation through in vitro and in vivo studies.