3, 5-Dihydroxy 4', 7-dimethoxyflavone-DNA interaction study for nucleic acid detection and differential cell staining.

The present study is focused on application of a natural compound, 3, 5-dihydroxy 4', 7-dimethoxyflavone (DHDM) from a medicinal plant Alpinia nigra for nucleic acid detection and differential cell staining. DHDM was found to interact with nucleic acid and forms complex, which was investigated for various applications. It was successfully utilized to visualize plasmid, genomic, and ds-linear DNA in agarose gel electrophoresis without affecting the DNA mobility in the gel. Fluorescence of DHDM increased several fold upon binding to dsDNA. Photostability of the compound was assessed and showed photobleaching effect that decreased gradually over time. Application of the compound was further extended to differential cell staining. When observed in fluorescence microscope, DHDM stained the dead cells and differentiated them from live cells in the case of bacterial, yeast, and mammalian cells. Higher concentration of the compound was found to be less cytotoxic to cancerous cells. Nucleic acid staining dyes like Ethidium bromide (EtBr), Propidium iodide (PI), etc. are carcinogens and environmental pollutants and therefore DHDM a natural compound, is a major benefit and thus can serve as an alternative to the current dyes.

Investigation of molecular interaction and conformational stability of disease concomitant to HLA-DRß3.

Human leucocyte antigen DRß3 is associated with specific autoimmune thyroid disease and plays a vital role in the progression of Grave's disease. The available crystallographic structure of the HLA DRA, DRß3*0101, was selected and used to generate mutation at position 57 from valine amino acid to Aspartic acid (D), Glutamic acid (E), Alanine (A), and Serine (S) amino acids by computational modeling approach. Mutant models were minimized, and stable conformation was chosen based on the lowest root mean square deviation value. Molecular docking assessed the best binding affinity of ligands C1, C2, C3, and C4 with wild-type and mutant HLA-DRß3 models. Molecular dynamics simulation studies were executed to evaluate the stability of selected hits with wild-type and mutant dock complexes. The C3 has shown good binding affinity with wild-type and selected mutants; V57A, V57E, and V57D. Structural and molecular dynamics insights reveal the differences between wild-type and mutant-type HLA-DRß3, which could help design novel antagonist molecules against autoimmune thyroid disorder.Communicated by Ramaswamy H. Sarma.

Antidiabetic Agents from Fungi with Special Reference to α-Glucosidase Inhibitors.

The enzyme α-glucosidases (EC 3.2.1.20) catalyzes the hydrolysis of α-1,4- glucopyranoside bond in oligosaccharides and disaccharides, and thus plays an essential role in regulating glucose content and the level of postprandial hyperglycemia. The inhibition of α-glucosidases is considered a viable strategy to develop new and effective antidiabetic drugs. Many patents like ZA201905405B; US9073897B2 have been published on α- glucosidase inhibitors. In recent years, several classes of fungal metabolites possessing a varying degree of α-glucosidases inhibitory activity have been reported. The primary chemical classes include xanthone, phenanthrene, terpenoid, coumarin, isocoumarin, naphthalene, piperazine, and polyketides. Few of the identified inhibitors exhibited severalfold better activities than well-known α-glucosidases inhibitor acarbose and can be used as a lead to develop new antidiabetic drugs. The present review highlights the recent development in the identification of α-glucosidases inhibitors from various fungal sources. Their chemical class, structures, and inhibitory activity in terms of IC50 or MIC are discussed here.

A rare case of hydatid cyst of the neck with concurrent pulmonary hydatid disease.

Echinococcosis, commonly known as hydatid disease, is a zoonotic infection caused by dog tapeworm Echinococcus granulosus. Hydatid disease of the head and neck region is scarcely reported even in endemic areas. We herein report a case with with neck swelling and respiratory symptoms subsequently diagnosed to have disseminated echinococcosis of the neck and left lung.

Supernumerary Tooth: Endoscopic Removal for a Rare Cause of Recurrent Epistaxis.

The presence of ectopic (supernumerary) teeth is common odontogenic problem in clinical practice. Its presence in dentate region is common but rare in the non dentate areas such as nose and maxillary sinus. The intranasal teeth generally remain asymptomatic but can get misdiagnosed for foreign body, or may present as complications like headache, epistaxis, nasal obstruction, rhinolith formation, oroantral fistula and sinusitis. Here, we discuss a case of intranasal tooth as a rare cause of profuse and recurrent epistaxis. The clinical, radiological findings and surgical treatment via endoscopic approach of this rare entity has been discussed. This interesting case report highlights the need to look beyond nose as cause for epistaxis. Endoscopic removal for this entity can be a preferred option to help minimize complications.

Head and Neck Lipomas at Uncommon Subsites: A Series of Four Cases.

Lipomas are benign soft tissue tumors; the most common ones present in subcutaneous planes distributed throughout the body. However, there are few sites which are unusual location for lipomas. Here, we discuss the presentation of 4 cases of head and neck lipomas at unusual subsites. Though its prevalence is high in the body, lipomas are rarely seen in upper aerodigestive tract and these lesions can cause severe deglutition and respiratory distress problems in addition to cosmetic deformities. In the head and neck, most common location of lipoma is the cheek, followed by the tongue. Tonsillar lipomas are very rare. The mainstay treatment for lipomas is complete surgical excision and recurrence following complete removal is rarely known. We are here discussing a series of 4 cases of lipomas, presenting at uncommon subsites in head and neck region. These include lesions over neck, tongue, palate and tonsillar fossa. Lipomas are benign mesenchymal tumors, that are initially non bothersome. However, with increasing size they can cause severe aerodigestive problems with functional compromise and need complete surgical excision.

Sarcoidosis presenting as bilateral optic neuritis after ChAdOx1 nCoV-19 vaccination.

Sarcoidosis is an idiopathic granulomatous disease and can virtually affect any organ system. Multiple factors, including tubercular antigens organic and environmental exposures, have been implicated in its pathogenesis. In addition to drugs, sarcoid-like reactions have been reported following varicella and influenza vaccination. Few reports of erythema nodosum and Lofgren syndrome have been reported after the COVID19 vaccination, though no histologic diagnosis was pursued in these cases. We herein report a case of sarcoidosis presenting with bilateral acute onset vision loss with a temporal association with COVID19 vaccination (ChadOx-1 n-COV, COVISHIELDTM). Symptoms started within two weeks of receiving the vaccine. Alternate causes for optic neuritis were excluded. Transbronchial lung biopsy showed the presence of non-caseating epithelioid cell granulomas. The patient received high-dose corticosteroids immediately after diagnosis, albeit with incomplete clinical improvement in vision on a three-month follow-up. In conclusion, we report a novel case of sarcoidosis-related optic neuritis following COVID19 vaccination.

Fabrication and evaluation of mannose decorated curcumin loaded nanostructured lipid carriers for hepatocyte targeting: In vivo hepatoprotective activity in Wistar rats.

Curcumin is a well-recognized antioxidant phytoactive isolated from the rhizomes of Curcuma longa. Numerous landmark investigations have proved the antioxidant and hepatoprotective potential of curcumin. The aim of present study was to target curcumin loaded nanocarriers to hepatocytes using asialoglycoprotein receptors targeting strategy. Mannose, a water-soluble carbohydrate, was hydrophobized by anchoring stearylamine with an objective to conjugate mannose on the surface of curcumin loaded nanostructured lipid carriers for targeting asialoglycoprotein receptors on hepatocytes. Mannose conjugated stearylamine was synthesized and characterized using various analytical techniques. The synthesized targeting ligand was incorporated curcumin loaded nanostructured lipid carriers and characterized by photon correlation spectroscopy. Zeta potential measurement was used to confirm the conjugation of the synthesized ligand to the surface of drug-loaded nanostructured lipid carriers. CCl4 induced hepatotoxicity in male Wistar rats was used as an experimental animal model to evaluate the hepatoprotective potential of formulated drug encapsulated nanostructured lipid carriers. The hepatoprotective potential was assessed by measuring serum liver injury markers and oxidative stress parameters in the liver post-mitochondrial supernatant. Mannose conjugated nanostructured lipid carriers showed acceptable particle size which revealed its suitability for hepatocyte targeting. In addition to this, mannose conjugated nanocarriers revealed significantly better (p â€‹< â€‹0.05) reduction of serum liver injury markers and proinflammatory cytokines compared to the unconjugated one which confirmed hepatocytes targeting potential of the synthesized ligand. Asialoglycoprotein receptors targeting could be a landmark strategy for hepatocyte targeting. Thus, the synthesized mannose anchored stearylamine could be a promising novel targeting ligand having hepatocyte targeting potential.

Synthesis and characterization of zinc derivatized 3, 5-dihydroxy 4', 7-dimethoxyflavone and its anti leishmaniasis activity against Leishmania donovani.

This study reports the synthesis and characterization of zinc derivatized 3,5-dihydroxy 4', 7- dimethoxyflavone (DHDM-Zn) compound for the development of new antileishmanial agents. The interaction studies of DHDM with zinc were carried out by UV spectra and fluorescence spectra analysis. Characterization of the complex was further accomplished by multi-spectroscopic techniques such as FTIR, Raman, HRMS, NMR, FESEM-EDX. The morphological and topographical studies of synthesized DHDM-Zn were carried out using FESEM with EDX. Further, it was demonstrated that DHDM-Zn exhibited an excellent in vitro antagonistic effect against the promastigote form of L. donovani. In addition, the possible mechanisms of promastigote L. donovani cell death, by involvement of derivatized compound in arrest of the cell cycle in the G1 phase and residual cell count reduction were investigated. Promastigote growth kinetics performed in the presence of the derivatized compound revealed a slow growth rate. The combination of growth kinetics and cell cycle analysis, made it possible to interpret and classify the cause of leishmanial cell death accurately. These results support that zinc derivatized complex (DHDM-Zn) might work as a lead compound for designing and developing a new antileishmanial drug.

Fungal Endophytes: A Potential Source of Antibacterial Compounds.

Antibiotic resistance is becoming a burning issue due to the frequent use of antibiotics for curing common bacterial infections, indicating that we are running out of effective antibiotics. This has been more obvious during recent corona pandemics. Similarly, enhancement of antimicrobial resistance (AMR) is strengthening the pathogenicity and virulence of infectious microbes. Endophytes have shown expression of various new many bioactive compounds with significant biological activities. Specifically, in endophytic fungi, bioactive metabolites with unique skeletons have been identified which could be helpful in the prevention of increasing antimicrobial resistance. The major classes of metabolites reported include anthraquinone, sesquiterpenoid, chromone, xanthone, phenols, quinones, quinolone, piperazine, coumarins and cyclic peptides. In the present review, we reported 451 bioactive metabolites isolated from various groups of endophytic fungi from January 2015 to April 2021 along with their antibacterial profiling, chemical structures and mode of action. In addition, we also discussed various methods including epigenetic modifications, co-culture, and OSMAC to induce silent gene clusters for the production of noble bioactive compounds in endophytic fungi.

Activation of Immune System May Cause Pathophysiological Changes in the Myocardium of SARS-CoV-2 Infected Monkey Model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an extremely contagious disease whereby the virus damages the host's respiratory tract via entering through the ACE2 receptor. Cardiovascular disorder is being recognized in the majority of COVID-19 patients; yet, the relationship between SARS-CoV-2 and heart failure has not been established. In the present study, SARS-CoV-2 infection was induced in the monkey model. Thereafter, heart tissue samples were collected, and pathological changes were analyzed in the left ventricular tissue by hematoxylin and eosin, trichrome, and immunohistochemical staining specific to T lymphocytes and macrophages. The findings revealed that SARS-CoV-2 infection induces several pathological changes in the heart, which cause cardiomyocyte disarray, mononuclear infiltrates of inflammatory cells, and hypertrophy. Furthermore, collagen-specific staining showed the development of cardiac fibrosis in the interstitial and perivascular regions in the hearts of infected primates. Moreover, the myocardial tissue samples displayed multiple foci of inflammatory cells positive for T lymphocytes and macrophages within the myocardium. These findings suggest the progression of the disease, which can lead to the development of severe complications, including heart failure. Additionally, SARS-CoV-2 antigen staining detected the presence of virus particles in the myocardium. Thus, we found that SARS-CoV-2 infection is characterized by an exaggerated inflammatory immune response in the heart, which possibly contributes to myocardial remodeling and subsequent fibrosis.

Comprehensive review on use of phospholipid based vesicles for phytoactive delivery.

Plant-derived phytoconstituents are well known for their therapeutic potential. It has been experimentally demonstrated that whole-plant extract or isolated phytoconstituents reveal various therapeutic potentials like hepatoprotective, antimicrobial, neuroprotective, antitumor, antioxidant, skin protectives, etc. Although these phytoconstituents have potential therapeutic benefits, their use is limited due to their poor bioavailability, stability in biological fluids, and authentication issues. These continue to be an open problem that affects the application of these valuable ancient herbal herbs in the effective treatment and management of various disease conditions. A potential solution to these difficult problems could be the loading of phytoactives in phospholipid-based vesicular systems. Phospholipid-based vesicles like liposomes, phytosomes, ethosomes as well as transfersomes were effectively utilized recently to solve drawbacks and for effective delivery of phytoactives. Several landmark studies observed better therapeutic efficacy of phytoactive loaded vesicles compared to conventional drug delivery. Thus phospholipid-based vesicles mediated phytoactive delivery is a recently developed promising and attractive strategy for better therapeutic control on disease conditions. The present short review highlights recent advances in herbal bioactive loaded phospholipid-based vesicles.

Recent Advances in the Discovery of Antiviral Metabolites from Fungi.

As the world manages the impact of a global pandemic caused by COVID-19, the discovery of new antiviral agents has become way more relevant and urgent. Viruses are submicroscopic infectious agents that replicate inside the living cells of different organisms. These viruses use nucleic acids (both DNA and RNA) for further replication and maturity inside the cells. Some of the viruses responsible for various human and plant diseases belong to the classes of Picornaviridae, Retroviridae, Orthomyxoviridae, Flaviviridae, Pneumoviridae, Virgaviridae, and Hepadnaviridae, and their treatment options are limited or non-existent. The consistent reemergence and resistance development in the viral strains demand the discovery and development of new antiviral drugs possessing better efficacy. Bio-active compounds isolated from fungi can be the source of new compounds with enhanced potency and new mechanisms of action. Fungi are known to produce a diverse lot of secondary metabolites due to their existence in harsh and testing climates which are often inhabitable for many organisms. Because of these unique environments, fungi produce a variety of secondary metabolites of different chemical classes like alkaloids, quinones, furanone, pyrones, benzopyranoids, xanthones, terpenes, steroids, peptides, and many acyclic compounds. Fungal metabolites are known to display a wide range of bioactive attributes, i.e., anticancer, antibacterial, antifungal, and anti-Alzheimer's, along with antiviral properties. In this review article, we report over 300 antiviral compounds from fungal sources during the period of 2009 to 2019. The source of these compounds is marine and endophytic fungi and they are arranged based on their antiviral action against different viral families. These compounds offer promise for their use and development as future antiviral drugs.

Anatomical study of hypospadias penis using magnetic resonance imaging in children.

INTRODUCTION: To assess the various anatomical patterns of the hypospadias penis, anatomical and histological study of the penile tissues, planes, and vascular patterns, and imagings such as ultrasound of penis, elastography, and Magnetic resonance imaging (MRI) of penis have been described in the literature. All these have been done to attempt the identification of anatomical variations that may influence surgical outcomes. There are very limited MRI studies of hypospadias penis to look for the pristine anatomy. OBJECTIVE: The objective was to identify anatomical variations in hypospadias penis such as the penile tissues and planes and the vascularity using MRI. MATERIAL AND METHODS: The total number of patients enrolled was 24 from January 2019 to July 2020. This included all the cases of hypospadias at any location aged ≥5 years. MRI penis was done using 3T (3 Tesla) MRI scanner (GE Healthcare signa 3T Scanner machine) with 3 mm body coil slice thickness and the surface coil of 3 inches. Non-contrast images were taken using fast spin-echo sequences in sagittal, coronal, and transverse planes. The findings analyzed were: presence and distribution of penile tissue and fascial structures, urethral plate thickness, and penile vasculature. RESULTS: The mean age was 7.62 ± 2.14 years. The types of hypospadias included were Coronal 1/24 (4.2%), Subcoronal 14/24 (58.3%), Distal penile 3/24 (12.5%), Midpenile 5/24 (20.8%) and Penoscrotal 1/24 (4.2%) (Summary Table 1). The mean urethral plate thickness was 1.33 ± 0.38 mm. The penile soft tissues were well visualized along with their fascial planes. The majority of patients (91.7%, 22/24) had Superficial Dartos vessels with both branches. Bulbourethral vessel was present in 18 (75.0%) cases but could not be visualized in the rest. Ventral and Lateral Dartos vessels were seen in 20 (83.3%) cases. Perforators distal to meatus were visualized in 21 (87.5%) cases and not visualized in 3 (1 each in Penoscrotal, Midpenile, and Coronal hypospadias). Collaterals at corona sulcus were visualized in 23 (95.8%) cases, at paraurethral spongiosum in 15 (62.5%) cases, and at dorsum in 22 (91.7%) cases. CONCLUSION: 3T MRI gives precise images in hypospadias with relation to the tissue and fascial planes of the penis. The vascular pattern visualization in these patients may be confirmed by the availability of a dedicated penile coil which will help to improve the resolution of the penile structures. Analyzing the penile vascular pattern and correlating it with surgical outcomes may aid the surgeon's knowledge of hypospadias, develop new surgical techniques and hence reduce complications.

Bacterial strains found in the soils of a municipal solid waste dumping site facilitated phosphate solubilization along with cadmium remediation.

Phosphate solubilizing bacteria (PSB) that can withstand high cadmium (Cd) stress is a desired combination for bioremediation. This study evaluated the Cd bioremediation potential of four PSB strains isolated from the contaminated soils of a municipal solid waste (MSW) discarding site (Guwahati, India). PSB strains were cultured in Pikovskaya (PVK) media, which led to higher acid phosphatase (ACP) activity and the release of organic acid. Optical density (OD) measurements were performed to determine the growth pattern of PSB; furthermore, Cd uptake by PSB was evaluated using infrared spectroscopy (IR) and X-Ray Diffraction (XRD) analyses. The 16S rRNA taxonomic analysis revealed that all the four promising PSB strains belonged to either Bacillus sp. or Enterobacter sp. One strain (SM_SS8) demonstrated higher tolerance towards Cd (up to 100 mg L-1). Flow cytometry analysis revealed 70.92%, 46.93% and 20.4% viability of SM_SS8 in 10, 50 and 100 mg L-1, respectively in PVK media containing Cd. This study has therefore substantiated the bioremediation of Cd from polluted soil by the PSB isolates. Thus, experimental results revealed a potential combo benefit, phosphate solubilization along with Cd remediation.

HOPX Plays a Critical Role in Antiretroviral Drugs Induced Epigenetic Modification and Cardiac Hypertrophy.

People living with HIV (PLWH) have to take an antiretroviral therapy (ART) for life and show noncommunicable illnesses such as chronic inflammation, immune activation, and multiorgan dysregulation. Recent studies suggest that long-term use of ART induces comorbid conditions and is one of the leading causes of heart failure in PLWH. However, the molecular mechanism of antiretroviral drugs (ARVs) induced heart failure is unclear. To determine the mechanism of ARVs induced cardiac dysfunction, we performed global transcriptomic profiling of ARVs treated neonatal rat ventricular cardiomyocytes in culture. Differentially expressed genes were identified by RNA-sequencing. Our data show that ARVs treatment causes upregulation of several biological functions associated with cardiotoxicity, hypertrophy, and heart failure. Global gene expression data were validated in cardiac tissue isolated from HIV patients having a history of ART. Interestingly, we found that homeodomain-only protein homeobox (HOPX) expression was significantly increased in cardiomyocytes treated with ARVs and in the heart tissue of HIV patients. Furthermore, we found that HOPX plays a crucial role in ARVs mediated cellular hypertrophy. Mechanistically, we found that HOPX plays a critical role in epigenetic regulation, through deacetylation of histone, while the HDAC inhibitor, Trichostatin A, can restore the acetylation level of histone 3 in the presence of ARVs.

Surgical Occlusion of Leaking Bronchus by a Serratus Anterior Flap in a Child with Langerhans Cell Histiocytosis.

Langerhans cell histiocytosis is an uncommon disease of childhood. Intrathoracic transposition flaps have been described for a management of number of conditions. We discuss our experience of the use of serratus anterior flap for the obliteration of a pulmonary bulla with a communicating airway, in a 1½-year-old pediatric patient with multisystem Langerhans cell histiocytosis who presented with recurrent pneumothorax with empyema due to rupture of bullae.

Congenital lateral facial teratoma: A case report and review of literature.

Facial teratomas are uncommon tumours in children that distort the face and may be associated with functional problems. They are less common than cervical teratomas though they are often grouped together and considered an emergency due to their tendency to cause respiratory compromise. They tend to be large and cause cosmetic issues; hence usually noticed early and medical help sought promptly by parents. The close proximity of facial teratomas to structures like eyes, parotid gland, facial nerve, vessels and brain makes them challenging and requires a patient and meticulous exploration during surgery. We present a case of an 11 month old girl with left sided temporal teratoma. Well planning of the incision and complete excision of the tumour with careful sparing of the facial nerves and parotid gland yielded good result.

A novel technique of abdominoplasty for prune belly syndrome.

Prune belly syndrome is an extremely rare congenital condition occurring predominantly in males. This triad syndrome comprises of partial or complete deficient abdominal wall muscles, undescended testes and dilated urinary collecting system. We present the case of a 2-year-old male patient, who presented with classic prune belly syndrome, operated with modification in classical Monfort technique of abdominoplasty. The basis of this approach was to save and use the supraumbilical abdominal wall which has better tensile strength. The infraumbilical skin was mostly discarded. The outcome was better in terms of cosmetic appearance as the scar was limited to the lower abdomen and better anterior abdominal wall strength.

Retained wooden foreign body in groin in a child: A case report and review of literature.

Wooden foreign body (WFB) injuries in children are common. They may report with acute presentation or be delayed as retained foreign body giving rise to complications. Cases with superficial skin penetration by these foreign bodies and acute presentation may be convenient to diagnose and remove. However, localising deeply impacted and chronically retained WFB is challenging, as they are usually not radiopaque and have a tendency to move deeper into the surrounding soft tissues with time. Foreign body retained for prolonged duration may present with either cellulitis, deep tissue infections, sinus, restriction of joint movements, necrotising fasciitis, osteomyelitis or tumour-like mass. We present an 8-year-old boy with discharging sinuses in the right iliac fossa and medial aspect of the right upper thigh, due to an impacted WFB for 3 months. Prompt radiological imaging and surgical removal helped him recover completely.