Coronavirus disease-2019 (COVID-19) is an infectious disease caused by SARS-CoV-2 virus. The microbes inhabiting the oral cavity and gut might play crucial roles in maintaining a favorable gut environment, and their relationship with SARS-CoV-2 infection susceptibility and severity is yet to be fully explored. This study investigates the diversity and species richness of gut and oral microbiota of patients with COVID-19, and their possible implications toward the severity of the patient's illness and clinical outcomes. Seventy-four (n = 74) clinical samples (gut and oral) were collected from 22 hospitalized patients with COVID-19 with various clinical conditions and 15 apparently healthy people (served as controls). This amplicon-based metagenomic sequencing study yielded 1,866,306 paired-end reads that were mapped to 21 phyla and 231 classified genera of bacteria. Alpha and beta diversity analyses revealed a distinct dysbiosis of the gut and oral microbial communities in patients with COVID-19, compared to healthy controls. We report that SARS-CoV-2 infection significantly reduced richness and evenness in the gut and oral microbiomes despite showing higher unique operational taxonomic units in the gut. The gut samples of the patients with COVID-19 included 46 opportunistic bacterial genera. Escherichia, Shigella, and Bacteroides were detected as the signature genera in the gut of patients with COVID-19 with diarrhea, whereas a relatively higher abundance of Streptococcus was found in patients with COVID-19 having breathing difficulties and sore throat (BDST). The patients with COVID-19 had a significantly lower abundance of Prevotella in the oral cavity, compared to healthy controls and patients with COVID-19 without diabetes, respectively. The altered metabolic pathways, including a reduction in biosynthesis capabilities of the gut and oral microbial consortia after SARS-CoV-2 infection, were also observed. The present study may, therefore, shed light on interactions of SARS-CoV-2 with resilient oral and gut microbes which might contribute toward developing microbiome-based diagnostics and therapeutics for this deadly pandemic disease.

Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF, we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.

Background. Multidrug-resistant (MDR) clones of Klebsiella pneumoniae (Kpn) have been increasingly documented in community-acquired and nosocomial infections all around the globe. Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamase enzymes derived from SHV genes by mutations. This research work aimed to investigate and analyze the widespread prevalence of Kpn antibiotic resistance in different areas of the southern part of Bangladesh. Methods. This particular study was executed and implemented by using 501 clinical samples or isolates from two different hospitals in Chattogram. The disk diffusion method was used to detect Kpn’s sensitivity to 16 antibiotics in a drug susceptibility test. By using the PCR technique, the widespread prevalence of antibiotic-resistant gene bla_SHV-11 was studied. Sequencing along with phylogenetic analysis was utilized to verify isolates with the bla_SHV-11 gene. Results. Almost all of the Kpn isolates were spotted to be antibiotic-resistant. These Kpn isolates were resistant to β-lactams, aminoglycosides, and quinolones at high levels. The spatial analysis displayed that infections involving Kpn were more common in the urban areas (70%) than in the rural areas (30%). Neonates had substantially higher levels ( ) of resistance to multidrug than other age groups. Cefepime was identified as the most frequent antibiotic-resistant to all age groups (56.68%). The highest numbers of resistant isolates (36.92%) were found in urine samples. The ESBL gene bla_SHV-11 was found in 38% isolates. Conclusion. The significant frequency of MDR Kpn harboring β-lactamases and AMR genes strongly suggests the requirement to develop effective antimicrobial resistance control and prevention measures in Bangladesh.

Vagal afferent stimulation exerts potent anti-inflammatory effects through neuroimmune pathways involving the sympathetic nervous system and spleen. However, how vagal afferent stimulation affects splenic responses and CellTrace-positive signals in inflamed tissues remains unclear. In this study, we investigated the effects of vagal afferent electrical stimulation (aVNS) on splenic responses and acute lung inflammation induced by intratracheal lipopolysaccharide (LPS) in mice. As a preconditioning intervention, aVNS was applied to the right cervical vagus nerve 24 h before LPS administration. Pulmonary inflammation was evaluated by measuring tumor necrosis factor-α (TNF-α) levels in bronchoalveolar lavage fluid. Splenic responses were assessed by measuring spleen weight, and CellTrace-positive signals were evaluated following direct intrasplenic injection of CellTrace™ Far Red. aVNS significantly reduced BALF TNF-α levels (sham: 5443 ± 404 pg/mL, n = 5; aVNS: 2891 ± 756 pg/mL, n = 5) following LPS administration. In addition, aVNS reduced spleen weight 24 h after stimulation. Furthermore, the ratio of CellTrace Far Red-positive cells was significantly higher in the aVNS + LPS group than in the sham + LPS group (0.00504 ± 0.00056 vs. 0.00151 ± 0.00017, n = 4 per group). These findings indicate that vagal afferent stimulation reduces the BALF TNF-α response to LPS and is associated with reduced spleen weight and increased CellTrace-positive objects detected in lung sections. These observations suggest that changes in splenic and immune-cell dynamics may accompany the anti-inflammatory effects of vagal afferent stimulation.