Oxalate nephropathy and chronic turmeric supplementation: a case report.

We present a case of a 69-year-old man who presented for routine check-up and was incidentally found to have kidney failure with an initially unrevealing history and bland urinary sediment. He was diagnosed with oxalate nephropathy in the setting of chronic turmeric supplementation and chronic antibiotic therapy with associated diarrhea. Our case provides several key insights into oxalate nephropathy. First, the diagnosis requires a high index of clinical suspicion. It is uncommonly suspected clinically unless there is an obvious clue in the history such as Roux-en-Y gastric bypass or ethylene glycol poisoning. Diagnosis can be confirmed by histopathologic findings and corroborated by serum levels of oxalate and 24-hour urinary excretion. Second, the diagnosis can often be missed by the pathologist because of the characteristics of the crystals unless the renal pathologist has made it a rule to examine routinely all H&E sections under polarized light. This must be done on H&E, as the other stains dissolve the crystals. Third, one oxalate crystal in a routine needle biopsy is considered pathologic and potentially contributing to the AKI or to the CKD in an important way. Fourth, secondary oxalosis can be largely mitigated or prevented in many cases, especially iatrogenic cases. This can come through the surgeon or the gastroenterologist providing proper instructions to patients on an oxalate-restricted diet or other specific dietary measures. Lastly, this case highlights the success that results from cooperation and communication between the pathologist and the treating physician.

New ring-A modified cycloartane triterpenoids from Dysoxylum malabaricum bark: Isolation, structure elucidation and their cytotoxicity.

The Genus Dysoxylum (Meliaceae) consists of approximately 80 species that are abundant in structurally diverse triterpenoids. The present study focused on isolating new triterpenoids from the bark of Dysoxylum malabaricum, one of the predominant species of Dysoxylum present in India. The methanol-dichloromethane bark extract was subjected to LCMS profiling followed by silica gel column chromatography and HPLC analysis to target new compounds. Two new ring A-modified cycloartane-type triterpenoids (1 and 2) were isolated from the bark extract. Spectroscopic methods like NMR, HRESIMS data, and electronic circular dichroism calculations elucidated the structuresandabsolute configurations of the isolated compounds. These compounds were evaluated for their cytotoxic potential against breast cancer cells and displayed notable cytotoxicity. Compound 1 exhibited the highest cytotoxicity against the MDA-MB-231 cells and induced apoptotic cell death. Also, it was able to inhibit glucose uptake and increase nitric oxide production in breast cancer cells.

Unveiling the cytotoxic and anti-proliferative potential of green-synthesized silver nanoparticles mediated by Colletotrichum gloeosporioides.

Fungal endophytes are a putative source of bioactive metabolites that have found significant applications in nanomedicine due to their metabolic versatility. In the present study, an aqueous extract of the fungal endophyte, Colletotrichum gloeosporioides associated with a medicinal plant Oroxylum indicum, has been used for the fabrication of green silver nanoparticles (CgAgNPs) and further evaluated their cytotoxic and anti-proliferative activity. Bioanalytical techniques including UV-Vis spectral analysis revealed a sharp band at 435 nm and functional molecules from the aqueous extract involved in the synthesis of CgAgNPs were evidenced through FTIR. Further, the crystalline nature of CgAgNPs was determined through XRD analysis and microscopy techniques including AFM, TEM and FESEM demonstrated the spherical shape of CgAgNPs exhibiting a crystalline hexagonal lattice and the size was found to be in the range of 9-29 nm. The significant cytotoxic potential of CgAgNPs was observed against breast cancer cells, MDA-MB-231 and MCF-7 with IC50 values of 18.398 ± 0.376 and 38.587 ± 1.828 µg mL-1, respectively. The biochemical study revealed that the treatment of MDA-MB-231 and MCF-7 cells with CgAgNPs reduces glucose uptake, suppresses cell proliferation, and enhances LDH release, indicating reduced cell viability and progression. Moreover, our research revealed differential expression of genes associated with apoptosis, cell cycle inhibition and metastasis suppression, evidencing anti-proliferative activity of CgAgNPs. The main objective of the present study is to harness anti-breast cancer activity of novel biogenic nanoparticles synthesized using the aqueous extract of O. indicum associated C. gloeosporioides and study the underlying mechanistic pathway exerted by these mycogenic nanoparticles.

Isolation and characterization of N-(2-Hydroxyethyl)hexadecanamide from Colletotrichum gloeosporioides with apoptosis-inducing potential in breast cancer cells.

Endophytic fungi are a well-established reservoir of bioactive compounds that are pharmaceutically valuable and therefore, contribute significantly to the biomedical field. The present study aims to identify the bioactive anticancer compound from ethyl acetate extract of fungal endophyte, Colletotrichum gloeosporioides associated with the leaf of the medicinal plant Oroxylum indicum. The fatty acid amide compound N-(2-Hydroxyethyl)hexadecanamide (Palmitoylethanolamide; PEA) was identified using antioxidant activity-guided fractionation assisted with tandem liquid chromatography coupled with quadrupole time of flight mass spectrometry, Fourier transform-infrared spectroscopy, time-of-flight mass spectrometry, and nuclear magnetic resonance. In-Silico molecular docking analysis showed that PEA potentially docked to the active sites of apoptosis-inducing proteins including BAX, BCL-2, P21, and P53. Further validation was done using in vitro study that showed PEA inhibitsthe proliferation, alters nuclear morphology and attenuates the wound closure ability of MDA-MB-231 and MCF-7 cells. PEA induces apoptosis via upregulating cell-cycle arrest (P21), tumor suppression (P53), pro-apoptotic (BAX, CASPASE-8, and FADD) genes, and downregulating anti-apoptotic gene BCL-2. The upregulation of the active form of Caspase-3 was also reported. This is the first-ever report for the isolation of PEA from C. gloeosporioides with anticancer activity against human breast cancer cells and therefore holds great potential for future therapeutics.

Complex Anal fistula treated with IFTAK (Interception of fistulous track with application of ksharsutra) technique- A case report.

BACKGROUND: An anal fistula is a common benign anorectal disease that tends to reoccur simple or low-type fistulas can be treated without affecting the sphincter mechanism; however, repairing a complex ano fistula without compromising anal continence can be difficult for a surgeon. CASE PRESENTATION: Here, we present an anal fistula of complex clinical appearance managed successfully by the IFTAK (Interception of fistulous track with application of ksharsutra) technique practiced at Banaras Hindu University, Varanasi, India. The diagnosis was made via visual and bi-manual digital rectal examination then confirmed by Endoanal ultrasonography (EAUS). The patient showed remarkable improvement and the fistula healed completely in due course of time without impairing the anal continence status of the patient. At four months of follow-up the patient was healthy and no recurrence was found. CONCLUSION: IFTAK is a minimally invasive technique and very effective in managing complex fistula in ano of cryptoglandular origin. The main cause of recurrence in complex anal fistula is non-identification of an infected anal crypt, secondary extensions, associated sepsis, or abscess at the time of examination or surgery. So, precise diagnosis and appropriate surgical measures play an equal role in the successful outcome of anal fistula treatment, failure to either will result in non-healing or recurrence.

Degradation product of curcumin restrain Salmonella typhimurium virulent protein L-asparaginase.

OBJECTIVES: Salmonella typhimurium is a pathogen responsible for causing a wide range of infectious diseases. The emergence of multi-drug resistance (MDR) in this microbe is a big challenge. L-asparaginase (less explored drug target) is selected as a drug target because it is actively involved in the virulence mechanism. To block this virulent enzyme, curcumin that is traditionally renowned for its medicinal properties was examined. However, its pharmacological behavior and targeting property is less understood because of its poor bioavailability. Therefore, the present work explores the antimicrobial effect of both curcumin and its degradation product against the MDR pathogen. METHODS: Molecular docking studies were carried out to evaluate the inhibitory effect of curcumin and its degradation product against the L-asparaginase enzyme using Schrodinger Maestro interface tools. The Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) profile of all the test ligands was also performed. RESULTS: The docking score of curcumin was -5.465 kcal/mol while its degradation product curcumin glucuronide has the lowest i.e., -6.240 kcal/mol. All the test ligands showed better or comparable docking scores with respect to control (Ciprofloxacin). Arg 142 and Asn 84 amino acid residues of L-asparaginase were found to be interacting with test ligands inside the binding pocket of the target protein. ADME/toxicology study also indicated the potency of curcumin/curcumin degradation products as a potent inhibitor. CONCLUSIONS: It was found that both curcumin and its degradation products have the potential to inhibit Salmonella. This information could be valuable for futuristic drug candidate development against this pathogen and could be a potential lead for mitigation of MDR.

COVID-19-associated Mucormycosis: A clinico-epidemiological study.

BACKGROUND: There was an unprecedented increase in COVID-19-associated-Mucormycosis (CAM) cases during the second pandemic wave in India. METHODS: This observational study was done to know the epidemiological profile of CAM cases andincluded all patients admitted with mucormycosis between May 2021 and July 2021. RESULTS: Out of the enrolled 208 CAM cases (either SARS-CoV-2 RT-PCR or serology positive), 204, three and one had rhino-orbital-cerebral, pulmonary and gastrointestinal mucormycosis, respectively. 95.7 % of the patients had diabetes, out of which 42.3 % were recently diagnosed. Mean HbA1c was 10.16 ± 2.56 %. 82.5 % of the patients were unvaccinated. During their COVID-19 illness, 86.5 % were prescribed antibiotics, 84.6 % zinc preparations, 76.4 % ivermectin, and 64.9 % steroids, while only 39.5 % required oxygen therapy. The frequency of blood groups A, B, O and AB in our CAM patients was 29.5 %, 18.9 %, 38.9 % &12.6 %, respectively. At three months follow up, 60 (28.8 %) patients died, four (1.9 %) stopped antifungal treatment, and 144(69.23 %) were on antifungal treatment. 55 % (n = 33) of deaths occurred within 15 days of admission. Mortality was significantly associated with higher age, RT-PCR positive for SARS-CoV-2, raised serum creatinine and alkaline phosphatase during treatment. At 6 months follow-up, eight more patients died, three due to chronic kidney disease, four patients who had stopped treatment and one patient who was on a ventilator due to COVID-19 associated pneumonia and the rest 140(67.3 %) survived. CONCLUSION: Uncontrolled hyperglycemia, SARS-CoV-2 infection, rampant use of antibiotics, zinc supplementation and steroids were some of the risk factors for mucormycosis. Despite the overwhelming number of patients with an uncommon disease like mucormycosis, the six months mortality was much lower than expected.

Bioprospecting of fungal endophytes from Oroxylum indicum (L.) Kurz with antioxidant and cytotoxic activity.

Oroxylum indicum (L.) Kurz, a medicinal plant, shows numerous pharmacological properties which may be attributed to the bioactive compounds produced by O. indicum or due to associated endophytes. In the present study, leaf of O. indicum was evaluated for the presence of associated fungal endophytes, and antioxidant and cytotoxic activities of bioactive compounds produced from them. Using culture-dependent approach, eight fungal endophytes belonging to five different genera were identified. Two endophytes Daldinia eschscholtzii and Ectophoma multirostrata have been reported for the first time from the leaf of O. indicum plant. High-performance thin-layer chromatography (HPTLC) of ethyl acetate (EA) extract of isolated fungal endophytes showed a distinct fingerprinting profile in EA extract of Colletotrichum gloeosporioides. Among identified endophytes, EA extract of C. gloeosporioides showed significant antioxidant activity against DPPH free radical, superoxide anion radical, nitric oxide radical and hydroxyl radical with EC50 values of 22.24±1.302 µg/mL, 67.46±0.576 µg/mL, 80.10±0.706 µg/mL and 61.55±1.360 µg/mL, respectively. EA extract of C. gloeosporioides exhibited potential cytotoxicity against HCT116, HeLa and HepG2 cancer cell lines with IC50 values of 76.59 µg/mL, 176.20 µg/mL and 1750.70 µg/mL, respectively. A comparative HPTLC fingerprinting and the antioxidant activity of C. gloeosporioides associated with two different hosts (leaf of O. indicum and dead twigs of other plant) showed that C. gloeosporioides produces bioactive compounds in a host-dependent manner.

Halocatena pleomorpha gen. nov. sp. nov., an extremely halophilic archaeon of family Halobacteriaceae isolated from saltpan soil.

A novel archaeal strain designated as SPP-AMP-1T was isolated from saltpan soil, using the serial dilution method on a halophilic archaeal medium supplemented with ampicillin. Cells were both rod-shaped and pleomorphic in nature, non-motile, unable to produce acid from a variety of sugars or grow anaerobically with different substrates (l-arginine) and electron acceptors (DMSO, nitrate). Optimal growth was observed at 42 °C, 3.4-4.2 M NaCl and pH 7.2. Cells did not lyse in distilled water and grew in the absence of Mg2+ ions. Phylogenetic analysis based on the sequences of 16S rRNA gene, amino acid sequence of ß'-subunit of RNA polymerase and 400 conserved proteins retrieved from the whole genome assemblies showed that strain SPP-AMP-1T was distantly related to any existing genera within the family Halobacteriaceae. MK-8 was the only quinone detected. Polar lipid analysis showed a unique combination of diethyl derivatives of phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, glycosyl-mannosyl-glucosyl diether and sulphated glycosyl-mannosyl-glucosyl diether as the major lipids. The G+C content of genomic DNA is 57.7 mol%. The phenotypic, phylogenetic and genomic data supported the concept of the novel genus status of strain SPP-AMP-1T in the family Halobacteriaceae for which the name Halocatena pleomorpha gen. nov., sp. nov., is proposed; the type strain is SPP-AMP-1T (=JCM 31368T=KCTC 4276T=MTCC 12579T).

Joint Consensus Statement of the Indian National Association for Study of the Liver and Indian Radiological and Imaging Association for the Diagnosis and Imaging of Hepatocellular Carcinoma Incorporating Liver Imaging Reporting and Data System.

Hepatocellular carcinoma (HCC) is the 6th most common cancer and the second most common cause of cancer-related mortality worldwide. There are currently no universally accepted practice guidelines for the diagnosis of HCC on imaging owing to the regional differences in epidemiology, target population, diagnostic imaging modalities, and staging and transplant eligibility. Currently available regional and national guidelines include those from the American Association for the Study of Liver Disease (AASLD), the European Association for the Study of the Liver (EASL), the Asian Pacific Association for the Study of the Liver, the Japan Society of Hepatology, the Korean Liver Cancer Study Group, Hong Kong, and the National Comprehensive Cancer Network in the United States. India with its large population and a diverse health infrastructure faces challenges unique to its population in diagnosing HCC. Recently, American Association have introduced a Liver Imaging Reporting and Data System (LIRADS, version 2017, 2018) as an attempt to standardize the acquisition, interpretation, and reporting of liver lesions on imaging and hence improve the coherence between radiologists and clinicians and provide guidance for the management of HCC. The aim of the present consensus was to find a common ground in reporting and interpreting liver lesions pertaining to HCC on imaging keeping LIRADSv2018 in mind.

Microbacterium aureliae sp. nov., a novel actinobacterium isolated from Aurelia aurita, the moon jellyfish.

The taxonomic position of a lemon-yellow-pigmented actinobacterium, strain JF-6T, isolated from Aurelia aurita, the moon jellyfish, collected from the Bay of Bengal coast, Kanyakumari, India, was determined using a polyphasic approach. The strain had phenotypic and chemotaxonomic properties that were consistent with its classification in the genus Microbacterium. Alignment of the 16S rRNA gene sequence of strain JF-6T with sequences from Microbacterium arthrosphaerae CC-VM-YT, Microbacterium yannicii G72T, Microbacterium trichothecenolyticum IFO 15077T, Microbacterium flavescens DSM 20643T, Microbacterium insulae DS-66T, Microbacterium resistens DMMZ 1710T and Microbacterium thalassium IFO 16060T revealed similarities of 98.95, 98.76, 98.43, 98.41, 98.41, 98.26 and 98.22 %, respectively. However, the levels of DNA-DNA relatedness with its closest phylogenetic neighbours confirmed that it represents a novel species within the genus. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol and an unknown glycolipid. The major menaquinones detected for strain JF-6T were MK-13 and MK-12. The diamino acid in the cell-wall peptidoglycan was ornithine and the peptidoglycan was type B2ß (Glu/Hyg-Gly-d-Orn). The DNA G+C content was 69.4 mol%. Based on these differences, strain JF-6T (=MTCC 11843T=JCM 30060T=KCTC 39828T) should be classified as the type strain of a novel species of Microbacterium, for which the name Microbacterium aureliae sp. nov. is proposed.

Systematic Imaging Module in Complete Hindgut Duplication.

Complete hind gut and anal canal duplication is a rare entity, usually remaining asymptomatic till the disease comes to light due to associated anomalies or due to cosmetic reasons. Classical imaging consisting of barium enema examination served a limited role, in terms of depicting the length of gut segment involved. Technical advances in magnetic resonance imaging (MRI) with three-dimensional (3D) reformations cannot only solve the above purpose but further evaluate key points needed for surgical planning. The present technical report lays out a systematic module for evaluation of various aspects of complete hindgut duplication, critical for management. The role of 3D MRI is emphasized upon, for evaluation of pelvic floor and anorectum, even in infants with a distorted anatomy.