Mitigation of Fibrosis after Myocardial Infarction in Rats by Using a Porcine Cholecyst Extracellular Matrix.

Fibrosis that occurs after nonfatal myocardial infarction (MI) is an irreversible reparative cardiac tissue remodeling process characterized by progressive deposition of highly cross-linked type I collagen. No currently available therapeutic strategy prevents or reverses MI-associated fibrotic scarring of myocardium. In this study, we used an epicardial graft prepared of porcine cholecystic extracellular matrix to treat experimental nonfatal MI in rats. Graft-assisted healing was characterized by reduced fibrosis, with scanty deposition of type I collagen. Histologically, the tissue response was associated with a favorable regenerative reaction predominated by CD4-positive helper T lymphocytes, enhanced angiogenesis, and infiltration of proliferating cells. These observations indicate that porcine cholecystic extracellular matrix delayed the fibrotic reaction and support its use as a potential biomaterial for mitigating fibrosis after MI. Delaying the progression of cardiac tissue remodeling may widen the therapeutic window for management of scarring after MI.

Kimura Disease in an Adult Indian Female, A Rare Presentation: A Novel Treatment with a Review of Literature.

Kimura disease (KD) is a chronic inflammatory disorder, which is quite rare and has an unclear and much debated etiology. KD is characterized by painless, nodular, subcutaneous swellings along with lymphadenopathy, encountered in the head and neck region more often. It is also known to affect major salivary glands. It is also associated with elevated Immunoglobulins (IgE) and peripheral blood and tissue eosinophilia. Kimura disease generally affects young Asian males. There is considerable difficulty in arriving at clinical diagnosis and often it is frustrating to both patients and the treating physicians because of the difficulty in its management. We are presenting and reporting a case of Kimura disease in a young adult Indian female patient who presented with a swelling in the left parotid region. We have successfully managed this patient medically with a unique combination of drugs, most of which have already been tried and reported in literature by various authors.

Ethyl palmitate, an anti-chikungunya virus principle from Sauropus androgynus, a medicinal plant used to alleviate fever in ethnomedicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Sauropus androgynus is a medicinal shrub used for the treatment of fever in ethnomedical traditions in various Southeast Asian countries. AIM OF THE STUDY: This study was aimed to identify antiviral principles from S. androgynus against Chikungunya virus (CHIKV), a major mosquito-borne pathogen that re-emerged in the last decade, and to unravel their mechanism of action. MATERIALS AND METHODS: Hydroalcoholic extract of S. androgynus leaves was screened for anti-CHIKV activity using cytopathic effect (CPE) reduction assay. The extract was subjected to activity guided isolation and the resultant pure molecule was characterized by GC-MS, Co-GC and Co-HPTLC. The isolated molecule was further evaluated for its effect by plaque reduction assay, Western blot and immunofluorescence assays. In silico docking with CHIKV envelope proteins and molecular dynamics simulation (MD) analyses were used to elucidate its possible mechanism of action. RESULTS: S. androgynus hydroalcoholic extract showed promising anti-CHIKV activity and its active component, obtained by activity guided isolation, was identified as ethyl palmitate (EP), a fatty acid ester. At 1 µg/mL, EP led to 100% inhibition of CPE and a significant 3 log10 reduction in CHIKV replication in Vero cells at 48 h post-infection. EP was highly potent with an EC50 of 0.0019 µg/mL (0.0068 µM) and a very high selectivity index. EP treatment significantly reduced viral protein expression, and time of addition studies revealed that it acts at the stage of viral entry. A strong binding to the viral envelope protein E1 homotrimer during entry, thus preventing viral fusion, was identified as a possible mechanism by which EP imparts its antiviral effect. CONCLUSIONS: S. androgynus contains EP as a potent antiviral principle against CHIKV. This justifies the use of the plant against febrile infections, possibly caused by viruses, in various ethnomedical systems. Our results also prompt more studies on fatty acids and their derivatives against viral diseases.

Perioperative Anticoagulation in Patients with Cancer.

PURPOSE OF REVIEW: There is a paucity of evidence for managing perioperative anticoagulation in patients with cancer. This review aims to provide clinicians who provide care for patients with cancer an overview of the available information and strategies needed to provide optimal care in a perioperative setting. RECENT FINDINGS: There is new evidence available around the management of perioperative anticoagulation in patients with cancer. The new literature and guidance were analyzed and summarized in this review. Management of perioperative anticoagulation in individuals with cancer is a challenging clinical dilemma. The approach to managing anticoagulation requires clinicians to review both disease and treatment specific patient factors that can contribute to both thrombotic and bleed risks. A thorough patient-specific assessment is essential in ensuring patients with cancer receive appropriate care in the perioperative setting.

Prevalence and Associated Factors of Depression and Anxiety Among Healthcare Workers During the COVID-19 Pandemic.

Cases and death counts rise as the world continues to scuffle with the COVID-19 pandemic and its catastrophic effects. Healthcare workers (HCWs) are at a heightened risk of developing psychological distress during the pandemic as a result of extreme work demands and poor experiences of recovery. This study aimed to evaluate the mental health outcomes of HCWs in hospitals during the pandemic and explore the associated psychosocial, individual, and work-related factors of depression and anxiety among them. The present study employed a cross-sectional survey study design. Participants from the Department of Medicine, Department of Surgery, and Department of Emergency were recruited via an online based questionnaire. A validated screening tool, the Depression, Anxiety and Stress Scale (DASS-21) questionnaire was utilized to assess the status of anxiety and depression among the HCWs. The prevalence of anxiety and depression among the HCWs were 12.2% and 1.4%, respectively. Multiple logistic regression analysis further demonstrated that being male (OR = 1.581) and having work-related stigma was significantly associated with anxiety (OR = 2.635).

A porcine cholecystic extracellular matrix conductive scaffold for cardiac tissue repair.

Cardiac tissue engineering using cells, scaffolds or signaling molecules is a promising approach for replacement or repair of damaged myocardium. This study addressed the contemporary need for a conductive biomimetic nanocomposite scaffold for cardiac tissue engineering by examining the use of a gold nanoparticle-incorporated porcine cholecystic extracellular matrix for the same. The scaffold had an electrical conductivity (0.74 ± 0.03 S/m) within the range of native myocardium. It was a suitable substrate for the growth and differentiation of cardiomyoblast (H9c2) as well as rat mesenchymal stem cells to cardiomyocyte-like cells. Moreover, as an epicardial patch, the scaffold promoted neovascularisation and cell proliferation in infarcted myocardium of rats. It was concluded that the gold nanoparticle coated cholecystic extracellular matrix is a prospective biomaterial for cardiac tissue engineering.

Biology, Significance and Immune Signaling of Mucin 1 in Hepatocellular Carcinoma.

Mucin 1 (MUC 1) is a highly glycosylated tumor-associated antigen (TAA) overexpressed in hepatocellular carcinoma (HCC). This protein plays a critical role in various immune-mediated signaling pathways at its transcriptional and post-transcriptional levels, leading to immune evasion and metastasis in HCC. HCC cells maintain an immune-suppressive environment with the help of immunesuppressive tumor-associated antigens, resulting in a metastatic spread of the disease. The development of intense immunotherapeutic strategies to target tumor-associated antigen is critical to overcoming the progression of HCC. MUC 1 remains the most recognized tumor-associated antigen since its discovery over 30 years ago. A few promising immunotherapies targeting MUC 1 are currently under clinical trials, including CAR-T and CAR-pNK-mediated therapies. This review highlights the biosynthesis, significance, and clinical implication of MUC 1 as an immune target in HCC.

A natural outbreak of infectious spleen and kidney necrosis virus threatens wild pearlspot, Etroplus suratensis in Peechi Dam in the Western Ghats biodiversity hotspot, India.

A large-scale mortality of pearlspot, Etroplus suratensis was reported from Peechi Dam, an artificial tropical lake made for irrigation and drinking water supply in Kerala, India during 2018. This dam is located in the premises of Western Ghats, recognized as one of the biodiversity hotspots of the world. The objective of this study was to identify the aetiological agent of this large-scale mortality of E. suratensis by systematic diagnostic investigation and identification of the pathogen. Virus isolation was carried out on a species-specific pearlspot fin (PSF) cell line. Infected PSF cells showed cytopathic effects (CPEs) like cell shrinkage, rounding, enlargement, clustering, and subsequent detachment of cells with a high viral titre of 106⋅95 TCID50 ml-1 at 8 days post-inoculation (dpi). Histopathological examination of the fish showed the presence of numerous abnormal enlarged basophilic cells and intracytoplasmic eosinophilic inclusions in the liver. Moreover, transmission electron microscopy (TEM) analysis revealed the presence of large numbers of 125-132 nm viral particles in the spleen tissues. PCR amplification and phylogenetic analysis of the major capsid protein (MCP) gene sequence confirmed that the causative agent was infectious spleen and kidney necrosis virus (ISKNV) of the genus Megalocytivirus. The experimental infection recorded 86.7 ± 2.7% mortality in the E. suratensis (body weight 11.01 ± 2.7 g; body length 8.01 ± 2.23 cm) injected with 1 × 104⋅25 TCID50 ml-1 ISKNV per fish. Our detailed investigation provided definitive diagnosis of ISKNV in the severe mass mortality event in wild E. suratensis in Peechi Dam, India, adding one more species to expanding host range of ISKNV infection. The high mortality rate of ISKNV infection in pearlspot suggests the perilous nature of this disease, particularly among the wild fish population.

Immune gene expression and protective effects in goldfish (Carassius auratus L.) immunized with formalin-inactivated cyprinid herpesvirus-2 (CyHV-2) vaccine.

The goldfish hematopoietic necrosis viral disease (GHNVD) has led to worldwide economic losses in goldfish aquaculture. The present study has focused on the development of an inactivated vaccine for the cyprinid herpesvirus (CyHV-2) and to check the immunogenicity of the vaccine in the host. The fantail goldfish fin (FtGF) cell line was used in the propagation of the CyHV-2 and the viral titer obtained were of 107.8 TCID50/ml. Followed by the virus was inactivated using 0.1% formalin for 2 days. Various concentrations of formalin-inactivated CyHV-2 (1%, 0.7%, 0.5%, 0.3% and 0.1%) were studied in the FtGF cell line. Morphological changes were observed in the FtGF cell line in all other concentrations of formalin except 0.1% formalin-inactivated CyHV-2 vaccine. The goldfishes were intraperitoneally injected with 300 µl of vaccine and various immune gene responses were studied for a period of 30 days. The gene expression of the adaptive markers CD8, CD4, IFN-ϒ, the cytokines (IL-10, IL-12) was studied in kidney and spleen tissues. Formalin-inactivated CyHV-2 vaccine showed a significant up-regulation of the genes CD8 and IFN-ϒ by the 6th hr post-vaccination onwards. The experimental fish were challenged intraperitoneally with CyHV-2 virus of concentration 107.8 TCID50/ml after 30 days of post-vaccination. A significant difference in cumulative mortality rate was observed for the vaccinated fishes from the unvaccinated fishes. The relative percent survival for formalin immunized fish was 74.03%. Our results have proven that the formalin-inactivated vaccines were efficient and it resulted in triggering the immune gene expression in goldfish. The development and further enhanced studies for this vaccine will lead to a promising low-cost commercial vaccine for CyHV-2 viral infection.

Surface Modification of Polypropylene Mesh with a Porcine Cholecystic Extracellular Matrix Hydrogel for Mitigating Host Tissue Reaction.

Polypropylene (PP) meshes are widely used for repairing skeletal muscle defects like abdominal hernia despite the chances of undesirable pro-inflammatory tissue reactions that demand revision surgeries in about 45% of cases. Attempts have been made to address the problem by modifying the mesh surface and architecture. These procedures have yielded only incremental improvements in the management of overall postoperative complications, and the search for a clinically viable therapeutic strategy continues. This study deployed a tissue engineering approach for mitigating PP-induced adverse tissue reaction by dip-coating the mesh with a hydrogel formulation of the porcine cholecystic extracellular matrix (CECM). The biomaterial properties of the CECM hydrogel-coated PP (C-PP) meshes were studied and their biocompatibility was evaluated by in vitro and in vivo tests based on ISO standards. Further, the nature of tissue reactions induced by the hydrogel-coated mesh and a commercial PP hernia repair graft was compared in a rat model of partial-thickness abdominal wall defect. Histomorphologically, in comparison with the PP graft-induced tissue reaction, C-PP caused a favorable graft-acceptance response characterized by reduced numbers of pro-inflammatory M1 macrophages and cytotoxic lymphocytes. Remarkably, the differential inflammatory response of the C-PP graft-assisted healing was associated with a fibrotic reaction predominated by deposition of type I collagen rather than type III collagen, as desired during skeletal muscle repair. It was concluded that the CECM hydrogel is a potential biomaterial for surface modification of polymeric biomedical devices.

Gelatin-Modified Cholecyst-Derived Scaffold Promotes Angiogenesis and Faster Healing of Diabetic Wounds.

Compromised angiogenesis is a major factor contributing delayed wound healing in diabetic patients. Graft-assisted healing using synthetic and natural scaffolds supplemented with micromolecules for stimulating angiogenesis is the contemporary tissue engineering strategy for treating diabetic wounds. This study deployed the carbodiimide chemical reaction for coupling gelatin with a porcine cholecyst-derived scaffold (CDS) for enhancing angiogenesis. The modification was confirmed by the trinitrobenzene sulfonic acid assay and scanning electron microscopy. The gelatin-coupled CDS was more stable than the bare CDS in an in vitro proteolytic environment and allowed survival of keratinocytes (HaCaT), indicating its suitability for chronic skin wound application. The gelatin coupling brought significant improvement in the in vitro angiogenic potential of the CDS as evident from the enhanced viability of endothelial cells. An in ovo chorioallantoic membrane assay also demonstrated the angiogenic potential of the modified scaffold. Further, the modified scaffold promoted angiogenesis and aided faster healing of full-thickness excision wounds in streptozotocin-induced diabetic rats. It is concluded that the gelatin-coupled CDS is a potential advanced wound care material for treating diabetic wounds.

Antibiotic-resistant Enterobacteriaceae from diseased freshwater goldfish.

Goldfish farming gained more attention among the ornamental fishes in aquaculture industry. The occurrence of bacterial infections and further antimicrobial treatment lead to the major crisis of antibiotic resistance in aquaculture. We have isolated diverse enterobacteriaceae groups which affect the goldfish and identified their response towards 46 antimicrobials of 15 different classes. Thirteen significant bacterial isolates such as Edwardsiella tarda, Serratia marcescens, Klebsiella aerogenes, Proteus penneri, P. hauseri, Enterobacter cloacae, E. cancerogenus, E. ludwigii, Citrobacter freundii, E. coli, Kluyvera cryocrescens, Plesiomonas shigelloides and Providencia vermicola were recovered from the infected fish with the Shannon-wiener diversity index of 2.556. Multiple antibiotic resistance (MAR) index was found to be maximum for P. penneri (0.87) and minimum for C. freundii and E. cloacae (0.22), highlighting the hyper antibiotic selection pressure in the farm. The minimum concentration of antibiotics required to inhibit most of the resistant isolates was found to be > 256 mcg/ml. All the isolates were susceptible towards ciprofloxacin. Plasmid curing and further AMR tests could reveal the location of antibiotic resistance genes mainly as plasmids which determine the large extent of AMR spread through horizontal gene transfer. This study is the first of its kind to investigate the antimicrobial resistance profile of enterobacteriaceae recovered from goldfish, before and after plasmid curing.

Antidiabetes constituents, cycloartenol and 24-methylenecycloartanol, from Ficus krishnae.

Ficus krishnae stem bark and leaves are used for diabetes treatment in traditional medicines. Stem bark of F. krishnae was sequentially extracted with hexane, methanol and water, and these extracts were tested for their antihyperglyceamic activity by oral glucose tolerance test (OGTT) in overnight fasted glucose loaded normal rats. Hexane extract showed significant glucose lowering activity in OGTT, and the triterpene alcohols (cycloartenol+24-methylenecycloartanol) (CA+24-MCA) were isolated together from it by activity guided isolation and characterized by NMR and mass spectroscopy. The ratio of the chemical constituents CA and 24-MCA in (CA+24-MCA) was determined as 2.27:1.00 by chemical derivatization and gas chromatographic quantification. (CA+24-MCA) in high fat diet-streptozotocin induced type II diabetic rats showed significant antidiabetes activity at 1 mg/kg and ameliorated derailed blood glucose and other serum biochemical parameters. Cytoprotective activity of (CA+24-MCA) from glucose toxicity was evaluated in cultured RIN-5F cells by MTT assay and fluorescent microscopy. (CA+24-MCA) in in vitro studies showed enhanced cell viability in RIN-5F cells and significant protection of beta cells from glucose toxicity. Both in in vivo and in vitro studies (CA+24-MCA) showed enhancement in insulin release from the beta cells. In short term toxicity studies in mice (CA+24-MCA) did not show any conspicuous toxic symptoms. The combination of the phytosterols (CA+24-MCA) obtained through activity guided isolation of the stem bark of F. krishnae showed significant activity, and therefore is a promising candidate for new generation antidiabetes drug development.

Anti-inflammatory and anticancer activities of erythrodiol-3-acetate and 2,4-di-tert-butylphenol isolated from Humboldtia unijuga.

Humboldtia unijuga Bedd., endemic to Agasthyamala in Western Ghats in India, is traditionally used by local Kani tribes for chicken pox, head ache and snake bite. This study reports the isolation of erythrodiol-3-acetate (HU-1) and 2,4-di-tert-butylphenol (HU-2) from H. unijuga roots and their anti-inflammatory and anticancer activities in macrophage, skin and breast cancer cell lines. Effects of HU-1 and HU-2 treatments (50, 100 µg/mL) on gene expression profiles of pro-inflammatory cytokines TNFα, IL-6 and IL-1ß, and apoptosis genes p53 and caspase 7 were studied. HU-2 exerted a significantly superior anti-inflammatory effect compared to HU-1 in all three pro-inflammatory genes. HU-2 showed a superior dose dependent anticancer effect through activation of p53 gene over HU-1 in MCF-7 cells. HU-1 exhibited a dose dependent effect on caspase 7 gene in both cell lines while HU-2 was more effective in A431. HU-2 has potential for development as a novel anti-inflammatory and anticancer agent.

Supplementation of all trans retinoic acid ameliorates ethanol-induced endoplasmic reticulum stress.

CONTEXT: Molecular pathogenesis of chronic alcoholism is linked to increased endoplasmic reticulum stress. Ethanol is a competitive inhibitor of vitamin A metabolism and vitamin A supplementation aggravates existing liver problems. Hence, we probed into the impact of supplementation of all trans retinoic acid (ATRA), the active metabolite of vitamin A on ethanol-induced endoplasmic reticulcum stress. METHODS: Male Sprague-Dawley rats were divided into four groups - I: Control; II: Ethanol; III: ATRA; IV: ATRA + Ethanol. After 90 days the animals were sacrificed to study markers of lipid peroxidation in hepatic microsomal fraction and expression of ER stress proteins and apoptosis in liver. RESULTS AND CONCLUSION: Ethanol caused hepatic hyperlipidemia, enhanced microsomal lipid peroxidation, upregulated expression of unfolded protein response associated proteins and that of apoptosis. Ethanol also led to downregulation of retinoid receptors. ATRA supplementation reversed all these alterations indicating the decrease in ethanol-induced endoplasmic reticulum stress.

A gold nanoparticle coated porcine cholecyst-derived bioscaffold for cardiac tissue engineering.

Extracellular matrices of xenogeneic origin have been extensively used for biomedical applications, despite the possibility of heterogeneity in structure. Surface modification of biologically derived biomaterials using nanoparticles is an emerging strategy for improving topographical homogeneity when employing these scaffolds for sophisticated tissue engineering applications. Recently, as a tissue engineering scaffold, cholecyst derived extracellular matrix (C-ECM) has been shown to have several advantages over extracellular matrices derived from other organs such as jejunum and urinary bladder. This study explored the possibility of adding gold nanoparticles, which have a large surface area to volume ratio on C-ECM for achieving homogeneity in surface architecture, a requirement for cardiac tissue engineering. In the current study, gold nanoparticles (AuNPs) were synthesized and functionalised for conjugating with a porcine cholecystic extracellular matrix scaffold. The conjugation of nanoparticles to C-ECM was achieved by 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide/N-hydroxysuccinimide chemistry and further characterized by Fourier transform infrared spectroscopy, environmental scanning electron microscopy, energy dispersive X-ray spectroscopy and thermogravimetric analysis. The physical properties of the modified scaffold were similar to the original C-ECM. Biological properties were evaluated by using H9c2 cells, a cardiomyoblast cell line commonly used for cellular and molecular studies of cardiac cells. The modified scaffold was found to be a suitable substrate for the growth and proliferation of the cardiomyoblasts. Further, the non-cytotoxic nature of the modified scaffold was established by direct contact cytotoxicity testing and live/dead staining. Thus, the modified C-ECM appears to be a potential biomaterial for cardiac tissue engineering.

Acute ventricular rate control in atrial fibrillation and atrial flutter.

Atrioventricular node blocking agents including beta-adrenergic blockers, non-dihydropyridine calcium channel blockers and digoxin are usually effective in controlling ventricular rate in atrial fibrillation and flutter. Intravenous beta-blockers and non-dihydropyridine calcium channel blockers are equally effective in rapidly controlling the ventricular rate. The addition of digoxin to the regimen causes a favorable outcome but digoxin as a single agent is generally less effective in slowing the ventricular rate in acute setting. Clonidine, magnesium, and amiodarone have also been used for acute ventricular rate control in atrial fibrillation. Limited data suggest that combination regimens provide better ventricular rate control than any agent alone. The agent of first choice is usually individualized depending upon the clinical situation. Beta-blockers are preferable in patients with myocardial ischemia, myocardial infarction and hyperthyroidism and in post-operative state, but should be avoided in patients with bronchial asthma and chronic obstructive pulmonary disease where non-dihydropyridine calcium channel blockers are preferred. Beta-blockers are preferred drugs used for acute ventricular rate control in atrial fibrillation during pregnancy. In atrial fibrillation with Wolff-Parkinson-White syndrome, beta-blockers, calcium channel blockers and digoxin should be avoided, as these drugs are selective atrioventricular node blockers without slowing conduction through the accessory pathway, which can lead to increased transmission of impulses preferentially through the accessory pathway and precipitate ventricular fibrillation. The drug of choice for atrial fibrillation in pre-excitation syndrome is procainamide but propafenone, flecainide and disopyramide have also been used. When clinical condition is unstable or patient is hemodynamically compromised, immediate electrical cardioversion is the treatment of choice, as the best measure to control ventricular rate is by conversion to sinus rhythm. Factors precipitating rapid ventricular rate should be treated as well.

Gender significance of ST-segment deviation detected by ambulatory (Holter) monitoring.

OBJECTIVE: To evaluate the gender influence in diagnostic and prognostic value of Holter-detected ST-segment deviation. METHODS: Two-hundred seventy-seven consecutive patients (196 men) who underwent coronary angiography for evaluation of chest pain were studied with 24-h Holter monitoring within 72 h of coronary angiography, and were followed up for 65+/-21 months. RESULTS: Men had a higher prevalence of coronary artery disease (169 of 196, 86%) compared to that of women (54 of 81, 67%), p<0.00025. Thirty-three (17%) men and 15 (19%) women had ST-segment deviation during 24-h recording. The sensitivity, specificity and positive predictive values of ST-segment deviation (elevation, depression, or both) for the detection of significant coronary artery disease were similar in men and women. The negative predictive values were significantly higher in women than men for ST-segment deviation (36% vs. 15%, p<0.001), ST-segment elevation (35% vs. 14%, p<0.001), and ST-segment depression (34% vs. 15%, p<0.001). Similarly, the diagnostic accuracies were significantly higher in women than men for ST-segment deviation (44% vs. 29%, p<0.025), ST-segment elevation (38% vs. 19%, p<0.001), and ST-segment depression (40% vs. 24%, p<0.025). There was no significant difference in composite end-point of events (mortality, nonfatal myocardial infarction, unstable angina, and coronary revascularization) in men versus women with ST-segment deviation (elevation, depression, or both). CONCLUSION: Holter-detected ST-segment deviation has a higher negative predictive value and diagnostic accuracy for detection of significant coronary artery disease in women than in men, although the prognostic values are not significantly different between men and women.