Thymoquinone mitigates obesity and diabetic parameters through regulation of major adipokines, key lipid metabolizing enzymes and AMPK/p-AMPK in diet-induced obese rats.

The present study was designed to evaluate the anti-obesity and anti-hyperglycemic activity of Thymoquinone (ThyQ) isolated from Nigella sativa seeds. Male Wistar rats were randomly divided into five groups and fed either normal pellet diet or high-fat diet (HFD) for 18 weeks and water ad-libitum. Group I: normal pellet diet (NPD)-fed, Group II: high-fat diet (HFD)-fed, Group III: HFD-fed-ThyQ (20 mg)-treated, Group IV: HFD-fed-ThyQ (40 mg)-treated and Group V: HFD-fed-Orlistat (5 mg)-treated group. Intervention with ThyQ started from 12th week onwards to HFD-fed rats of group III and IV. ThyQ administration significantly (p < 0.01) mitigated body weight gain, blood glucose, insulin level, serum and liver lipids (except HDL) and improved glucose tolerance and insulin sensitivity as evaluated by oral glucose tolerance test (OGTT), homeostasis model assessment-insulin resistance (HOMA-IR) and insulin tolerance test (ITT). Furthermore, ThyQ significantly (p < 0.01) diminished serum aspartate transaminase (AST), alanine transaminase (ALT), acetyl-CoA carboxylase (ACC), plasma leptin, resistin and visfatin levels but enhanced lipoprotein lipase (LPL) and adiponectin levels. RT-PCR analysis demonstrated down-regulated mRNA expression of sterol regulatory element-binding proteins-1c (SREBP-1c), CCAAT/enhancer-binding protein-α (C/EBP-α) and fatty acid synthase (FAS) but upregulation of Insulin receptor substrate-1 (IRS-1).Western blot analysis displayed phosphorylation of adenosine monophosphate activated protein kinase (AMPK) in ThyQ-treated rats. Liver microtome sections of HFD-fed rats showed degenerated hepatocytes with high lipid stores while that of adipose tissue sections displayed large, fat-laden adipocytes, however, these histological changes were considerably attenuated in ThyQ-treated groups. Together these findings demonstrate that ThyQ can be a valuable therapeutic compound to potentially alleviate diet-induced obesity, hyperglycemia and insulin resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03847-x.

Rapid Synthesis of Kaolinite Nanoscrolls through Microwave Processing.

Kaolinite nanoscrolls (NScs) are halloysite-like nanotubular structures of great interest due to their ability to superimpose halloysite's properties and applicability. Especially attractive is the ability of these NScs to serve as reaction vessels for the uptake and conversion of different chemical species. The synthesis of kaolinite NScs, however, is demanding due to the various processing steps that lead to extended reaction times. Generally, three intercalation stages are involved in the synthesis, where the second step of methylation dominates others in terms of duration. The present research shows that introducing microwave processing throughout the various steps can simplify the procedure overall and reduce the synthesis period to less than a day (14 h). The kaolinite nanoscrolls were obtained using two final intercalating agents, aminopropyl trimethoxy silane (APTMS) and cetyltrimethylammonium chloride (CTAC). Both produce abundant NScs, as corroborated by microscopy measurements as well as the surface area of the final products; APTMS intercalated NScs were 63.34 m2/g, and CTAC intercalated NScs were 73.14 m2/g. The nanoscrolls averaged about 1 µm in length with outer diameters of APTMS and CTAC intercalated samples of 37.3 ± 8.8 nm and 24.9 ± 6.1 nm, respectively. The availability of methods for the rapid production of kaolinite nanoscrolls will lead to greater utility of these materials in technologically significant applications.

Percutaneous vertebroplasty for symptomatic osteoporotic compression fractures: A single-center prospective study.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCFs) increasingly occur with advancing age, and are associated with significant morbidity, mortality, and cost. We assessed the clinical efficacy, radiological, and functional outcomes for patients undergoing percutaneous vertebroplasty (PVP) due to OVCFs, with a special focus on the frequency of new vertebral compression fractures (VCFs). METHODS: This study, carried from 2018 to 2020, included 22 females and 4 males. They averaged 60.15 years of age (range, 50-70) were followed an average of 14.5 months (range 12-36 months), and had 30 VCFs between the T7-L2 levels. Multiple variables were studied, including; anterior vertebral height (AVH) and kyphotic angle (KA), new VCFs, and functional outcomes. RESULTS: The postoperative Visual Analog Scale and Oswestry Disability Index were significantly reduced at 12 months after PVP. Improvements for AVH and KA were also statistically significant; 23 patients (88.46%) had a dramatic decrease in pain on post-operative day 1, while 3 patients (11.53%) had no decrease in pain after PVP on post-operative day 1-1 postoperative month. No major complications were observed except high incidence of cement leakage at 8 levels (26.67%) in 6 patients. Additionally, new VCFs occurred in 10 vertebrae in 8 patients (30.76%), involving 6 adjacent (60%), and 4 nonadjacent vertebrae (40%). CONCLUSION: PVP is an effective procedure in the management of painful OVCFs refractory to medical treatment. These PVP procedures yield immediate vertebral stabilization, relieve pain, and restore function with minimal associated morbidity.

Management of post-operative discitis following discectomy in a tertiary-level hospital.

PURPOSE: To perform retrospective analysis of 75 post-operative disc space infections after open lumbar discectomy (OLD) and to assess the outcome of their medical and surgical management in a tertiary-level hospital. METHODS: Records of 50 men and 25 women aged 26-65 (mean, 42.53) years who underwent treatment for post-operative discitis (POD) after single level OLD at L3-4 (n = 8), L4-5 (n = 42), L5-S1 (n = 25) level. The POD was diagnosed according to specific clinical signs, laboratory and radiographic investigations and all of them received initial intravenous antibiotics (IVA) for at least 4-6 weeks followed by oral ones. Successful responders (n = 55) were considered in Group-C and remainder [Group-S (n = 20)] were operated at least after 4 weeks of failure. Demographic data, clinical variables, hospital stay, duration of antibiotic treatment and post-treatment complications were collected from the hospital record and assessment before and after treatment were done by using visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) score. Comprehensive outcome was evaluated by modified criteria of Kirkaldy-Willis. RESULTS: The mean follows up was 36.38 months. Significant improvement of mean VAS and JOA score was achieved in both conservative (76.36% satisfactory) and operative (90% satisfactory) groups although the difference was statistically insignificant. CONCLUSION: Although insignificant, early surgical intervention provided better results (e.g. functional outcomes, length of hospital stay and duration of antibiotic treatment therapy) than conventional conservative treatment in post-operative discitis.

Lumbar revision microdiscectomy in patients with recurrent lumbar disc herniation: A single-center prospective series.

BACKGROUND: Recurrent lumbar disc herniation (RLDH) is a common complication following primary microdiscectomy. Notably, revision surgery for recurrent disc herniation typically warrants "aggressive discectomy (AD)" rather than microdiscectomy due to the marked changes in anatomy, including postoperative scar. Here, we prospectively evaluated clinical outcomes of 22 RLDH patients following secondary aggressive discectomy (AD). METHODS: Records of 15 males and seven females averaging 41.7 years of age (range 21-60) who developed RLDH following primary microdiscectomy at the L4-5 (n = 12) and L5-S1 (n = 10) levels were studied. All patients underwent secondary AD for recurrent lesions (2014-2019). Multiple clinical parameters were assessed for these 22 patients. Outcomes were evaluated an average of 28.8 months postoperatively and included assessment of visual analog scales (VASs) and Japanese Orthopedic Association (JOA) Scores. RESULTS: The VAS scores for back and radicular pain significantly improved, as did the JOA scores following surgery in all 22 patients after secondary AD. CONCLUSION: The authors concluded that secondary conventional revision discectomy (e.g., AD) effectively and safely managed RLDH.

Diversity and genomic determinants of the microbiomes associated with COVID-19 and non-COVID respiratory diseases

The novel coronavirus disease 2019 (COVID-19) is a rapidly emerging and highly transmissible disease caused by the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2). Understanding the microbiomes associated with the upper respiratory tract infection (URTI), chronic obstructive pulmonary disease (COPD) and COVID-19 diseases has clinical interest. We hypothesized that the diversity of microbiome compositions and their genomic features are associated with different pathological conditions of these human respiratory tract diseases (COVID-19 and non-COVID; URTI and COPD). To test this hypothesis, we analyzed 21 whole metagenome sequences (WMS) including eleven COVID-19 (BD = 6 and China = 5), six COPD (UK = 6) and four URTI (USA = 4) samples to unravel the diversity of microbiomes, their genomic features and relevant metabolic functions. The WMS data mapped to 534 bacterial, 60 archaeal and 61 viral genomes with distinct variation in the microbiome composition across the samples (COVID-19>COPD>URTI). Notably, 94.57%, 80.0% and 24.59% bacterial, archaeal and viral genera shared between the COVID-19 and non-COVID samples, respectively, however, the COVID-19 related samples had sole association with 16 viral genera other than SARS-CoV-2. Strain-level virome profiling revealed 660 and 729 strains in COVID-19 and non-COVID sequence data, respectively and of them 34.50% strains shared between the conditions. Functional annotation of metagenomics sequences of thevCOVID-19 and non-COVID groups identified the association of several biochemical pathways related to basic metabolism (amino acid and energy), ABC transporters, membrane transport, replication and repair, clustering-based subsystems, virulence, disease and defense, adhesion, regulation of virulence, programmed cell death, and primary immunodeficiency. We also detected 30 functional gene groups/classes associated with resistance to antibiotics and toxic compounds (RATC) in both COVID-19 and non-COVID microbiomes. Furthermore, a predominant higher abundance of cobalt-zinc-cadmium resistance (CZCR) and multidrug resistance to efflux pumps (MREP) genes were detected in COVID-19 metagenome. The profiles of microbiome diversity and associated microbial genomic features found in both COVID-19 and non-COVID (COPD and URTI) samples might be helpful for developing the microbiome-based diagnostics and therapeutics for COVID-19 and non-COVID respiratory diseases. However, future studies might be carried out to explore the microbiome dynamics and the cross-talk between host and microbiomes employing larger volume of samples from different ethnic groups and geoclimatic conditions.

Host range projection of SARS-CoV-2: South Asia perspective

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causing agent of Coronavirus Disease-2019 (COVID-19), is likely to be originated from bat and transmitted through intermediate hosts. However, the immediate source species of SARS-CoV-2 has not yet been confirmed. Here, we used diversity analysis of the angiotensin I converting enzyme 2 (ACE2) that serves as cellular receptor for SARS-CoV-2 and transmembrane protease serine 2 (TMPRSS2), which has been proved to be utilized by SARS-CoV-2 for spike protein priming. We also simulated the structure of receptor binding domain of SARS-CoV-2 spike protein (SARS-CoV-2 S RBD) with the ACE2s to investigate their binding affinity to determine the potential intermediate animal hosts that could spread the SARS-CoV-2 virus to humans in South Asia. We identified cow, buffalo, goat and sheep, which are predominant species in the household farming system in South Asia that can potentially be infected by SARS-CoV-2. All the bird species studied along with rat and mouse were considered less potential to interact with SARS-CoV-2. The interaction interfaces of SARS-CoV-2 S RBD and ACE2 protein complex suggests pangolin as a potential intermediate host in SARS-CoV-2. Our results provide a valuable resource for the identification of potential hosts for SARS-CoV-2 in South Asia and henceforth reduce the opportunity for a future outbreak of COVID-19.

Host transcriptional responses and SARS-CoV-2 isolates from the nasopharyngeal samples of Bangladeshi COVID-19 patients

As the COVID-19 pandemic progresses, fatality and cases of new infections are also increasing at an alarming rate. SARS-CoV-2 follows a highly variable course and it is becoming more evident that individuals immune system has a decisive influence on the progression of the disease. However, the detailed underlying molecular mechanisms of the SARS-CoV-2 mediate disease pathogenesis are largely unknown. Only a few host transcriptional responses in COVID-19 have been reported so far from the Western world, but no such data has been generated from the South-Asian region yet to correlate the conjectured lower fatality around this part of the globe. In this context, we aimed to perform the transcriptomic profiling of the COVID-19 patients from Bangladesh along with the reporting of the SARS-CoV-2 isolates from these patients. Moreover, we performed a comparative analysis to demonstrate how differently the various SARS-CoV-2 infection systems are responding to the viral pathogen. We detected a unique missense mutation at 10329 position of ORF1ab gene, annotated to 3C like proteinase, which is found in 75% of our analyzed isolates; but is very rare globally. Upon the functional enrichment analyses of differentially modulated genes, we detected a similar host induced response reported earlier; this response was mainly mediated by the innate immune system, interferon stimulation, and upregulated cytokine expression etc. in the Bangladeshi patients. Surprisingly, we did not perceive the induction of apoptotic signaling, phagosome formation, antigen presentation and production, hypoxia response within these nasopharyngeal samples. Furthermore, while comparing with the other SARS-CoV-2 infection systems, we spotted that lung cells trigger the more versatile immune and cytokine signaling which was several folds higher compared to our reported nasopharyngeal samples. We also observed that lung cells did not express ACE2 in a very high amount as suspected, however, the nasopharyngeal cells are found overexpressing ACE2. But the amount of DPP4 expression within the nasal samples was significantly lower compared to the other cell types. Surprisingly, we observed that lung cells express a very high amount of integrins compared to the nasopharyngeal samples, which might suggest the putative reasons for an increased amount of viral infections in the lungs. From the network analysis, we got clues on the probable viral modulation for the overexpression of these integrins. Our data will provide valuable insights in developing potential studies to elucidate the roles of ethnicity effect on the viral pathogenesis, and incorporation of further data will enrich the search of an effective therapeutics.

Epidemiology of Imported Malaria in Netrokona District of Bangladesh 2013-2018: Analysis of Surveillance Data.

INTRODUCTION: Netrokona is one of the first phase malaria elimination targeted 8 districts of Bangladesh by 2021. The district constitutes only 7% of the population but contributes half of the malaria cases in that area. Most of the cases of that district are imported from Meghalaya State of India. The study was conducted to understand the epidemiology of these imported malaria cases for further strategy development to prevent both imported and introduced cases. METHODOLOGY: The study was retrospectively conducted on the malaria cases confirmed by microscopy and/or RDT by the government and/or NGO service providers between 2013 and 2018. The information of the cases was collected from the verbal "investigation" report of individual malaria confirmed cases. The respondents of the "investigation" were either the patients or their family members. Out of the 713 cases during the study period, descriptive analysis of 626 cases (based on the completeness of "investigation form") of the district was done using MS Excel version 2016. RESULTS: Proportion of imported malaria in Netrokona district increased from 60% in 2013 to 95% in 2018 which persists throughout the year with a little seasonal fluctuation. The overall contribution of these imported cases is 93% by cross-border workers by population type and 84%, 66%, and 95% by male, labour, and tribal population considering the factors of sex, occupation, and ethnicity, respectively. Population aged between 15 and 49 years contributed 82% of these imported cases. All of these cases occurred in the internationally bordering belt with Meghalaya State of India. Species-wise distribution revealed lower P. falciparum (63%) and higher mixed (28%) infection in imported cases compared to the 71% Pf and 20% mixed infection among the indigenous infections whereas P. vivax is similar in both cases. CONCLUSION: Imported malaria is an emerging issue that has a potential risk of increased local transmission which might be a challenge to malaria elimination in that area. Appropriate interventions targeting the cross-border workers are essential to prevent the introduced cases and subsequently avoid reestablishment when elimination of the disease is achieved.

Whole Leea macrophylla ethanolic extract normalizes kidney deposits and recovers renal impairments in an ethylene glycol-induced urolithiasis model of rats

OBJECTIVE@#To investigate the antilithiatic effect of the whole Leea macrophylla (L. macrophylla) Roxb (Leeaceae) ethanol extract in ethylene glycol-induced urolithiasis model of rats.@*METHODS@#Forty two seven weeks old male wistar albino rats were randomly divided into two major groups namely: preventive (n=18) and therapeutic (n=24). Preventive group was further subdivided into 3 groups of 6 rats namely: preventive control (PC), preventive lithiatic control (PLC) and preventive lithiatic L. macrophylla (PLLM). Similarly, therapeutic group was also subdivided into 4 groups of 6 rats namely: therapeutic control (TC), therapeutic lithiatic control (TLC), therapeutic lithitatic L. macrophylla (TLLM) and therapeutic lithiatic cystone (TLCYS). The lithiasis was induced by 0.75% (v/v) ethylene glycol in the drinking water of all groups except the PC and TC groups. The urinary ionic parameters such as calcium, inorganic phosphate, oxalate, magnesium & creatinine and renal morphology were altered by ethylene glycol, which were partially recovered by 14 d preventive and almost fully recovered by 28 d therapeutic intervention trials with L. macrophylla extract (500 mg/kg BW daily).@*RESULTS@#Significant difference on recovery was observed between preventive and therapeutic interventional trials. Anti-urolithiatic effect of cystone was significantly (P<0.001) higher than extracts. L. macrophylla extract was found nontoxic in the acute toxicity test.@*CONCLUSION@#The results of this study demonstrated very promising anti-urolithiatic effect of L. macrophylla extract with preventive and therapeutic treatments in this experimental condition.