Iron overload can contribute to the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH). Hepcidin (Hamp), which is primarily synthesized in hepatocytes, is a key regulator of iron metabolism. However, the role of Hamp in NASH remains unclear. Therefore, we aimed to elucidate the role of Hamp in the pathophysiology of NASH.

Male mice were fed a choline-deficient L-amino acid-defined (CDAA) diet for 16 weeks to establish the mouse NASH model. A choline-supplemented amino acid-defined (CSAA) diet was used as the control diet. Recombinant adeno-associated virus genome 2 serotype 8 vector expressing Hamp (rAAV2/8-Hamp) or its negative control (rAAV2/8-NC) was administered intravenously at week 8 of either the CDAA or CSAA diet.

rAAV2/8-Hamp treatment markedly decreased liver weight and improved hepatic steatosis in the CDAA-fed mice, accompanied by changes in lipogenesis-related genes and adiponectin expression. Compared with the control group, rAAV2/8-Hamp therapy attenuated liver damage, with mice exhibiting reduced histological NAFLD inflammation and fibrosis, as well as lower levels of liver enzymes. Moreover, α-smooth muscle actin-positive activated hepatic stellate cells (HSCs) and CD68-postive macrophages increased in number in the CDAA-fed mice, which was reversed by rAAV2/8-Hamp treatment. Consistent with the in vivo findings, overexpression of Hamp increased adiponectin expression in hepatocytes and Hamp treatment inhibited HSC activation.

Overexpression of Hamp using rAAV2/8-Hamp robustly attenuated liver steatohepatitis, inflammation, and fibrosis in an animal model of NASH, suggesting a potential therapeutic role for Hamp.

The SARS-CoV-2 virus Spike (S) protein binds to an angiotensin-converting-enzyme 2 receptor (ACE2) on the surface of cells to allow viral DNA entry. Given the plenitude of FDA-approved antiviral drugs, we aimed to screen those that may be repurposed for treating SARS-CoV-2 infections.

Using the crystal structure of SARS-CoV-2 Spike complexed with ACE2 (PDB ID: 6VW1) as a template, we developed a pharmacophore model of functional centers of the SARS-CoV-2 Spike protein inhibitor-binding domain. The conformations of these compounds underwent 3D fingerprint similarity clusterization, followed by docking of possible conformers to the binding site of ACE2. A similar protocol was followed for a set of randomly-selected compounds. Molecular dynamics was performed to confirm the stability of the selected drugs bound to ACE2.

Based on the model, we conducted a pharmacophore search from a conformational database of FDA-approved drugs. From the 379 compounds identified as potential inhibitors of SARS-CoV-2, 152 compounds with the best scores were selected based on maximal hydrogen-bond and hydrophobic interactions. The average free energies of the docking interaction for the selected compounds were better than those of random compounds. The obtained drug list includes inhibitors of HIV, HCV, CMV, ZIKV, HMPV, and RVFV as well as a set of drugs that have demonstrated some activity in MERS, SARS-CoV, and SARS-CoV-2 therapy.

Using a set of computational methods, we predicted the FDA-approved drugs that might bind to the interface of ACE2 protein and Spike protein of SARS-CoV-2 and prevent binding between Spike and ACE2. In further works, we recommend testing the selected compounds for treatment of COVID-19.

NKX3.1 is an emerging marker for tumors of prostatic origin; however, the utility and diagnostic values of NKX3.1 have not been broadly studied in cytology specimens. The purpose of this study is to determine the performance of NKX3.1, compared to prostatic specific antigen (PSA) and prostatic specific alkaline phosphatase (PSAP), as an organ-specific marker of metastatic prostatic adenocarcinoma (MPAC) in cytology specimens.

The cytology specimens, which had been evaluated to include or exclude MPAC, were collected from our pathology database. Immunostains for PSA, PSAP, and NKX3.1 were performed on cell block sections.

A total of 118 cases were collected. In 37 MPACs, NKX3.1 was diffusely positive in 34 cases (92%) and focally positive in 3 cases (8%). PSA indicated diffuse positivity in 16 cases (43%), focal positivity in 13 (35%) cases, and was negative in 8 (22%) cases. PSAP immunostain was performed in only 12 MPACs, showing diffuse positivity in 5 (42%), focal positivity in 3 (25%), and negativity in 4 (33%) cases. Among the 81 non-metastatic prostatic adenocarcinoma cases, NKX3.1 was negative in 80 (99%) cases and focally positive in only 1 (1%) case; all cases with available PSA and PSAP staining were negative. The calculated sensitivities for NKX3.1, PSA, and PSAP were 100%, 78%, and 67%, respectively, while the specificities were 99%, 100%, and 100%, respectively.

Compared to PSA and PSAP, NKX3.1 is more reliable as an individual marker for MPAC in cytology specimens. Combining NKX3.1 and PSA can be useful in some cases to enhance diagnostic utility.

Ascariasis remains a major burden of disease globally, with an estimated prevalence of 1 billion individuals being affected. Previous studies have highlighted a strong association and geographical overlap between worm infestation and TB infection. In these same studies, the occurrence of helminth-tuberculosis coinfection has been described and is postulated to be a result of immune modulation induced by both etiological organisms. An 81 year old male with history of laparoscopic cholecystectomy presented with acute pancreatitis and cholangitis. An abdominal Ultrasound was performed which excluded biliary dilatation and evidence of gall stones. Nevertheless, in view of a high index of suspicion of biliary obstruction, we proceeded with an Endoscopic Ultrasound (EUS) procedure which revealed multiple long, tubular, hyperechoic structures with an anechoic centre that spanned the entire length of the Common Bile Duct. The echogenic structures did not exhibit posterior acoustic shadowing and appeared mobile which was in keeping with biliary ascariasis. In addition, multiple large matted lymph nodes were observed at the periportal, hilar and -peripancreatic region. EUS-FNB of the biopsied hilar lymph node was in keeping with reactive lymphadenitis. Endoscopic Retrograde Cholangiopancreatography (ERCP) was subsequently performed and multiple linear imbricated, bile coated structures which was in keeping with macerated worms were trawled out from the CBD. Patient was given Albendazole therapy and repeat endoscopic evaluation revealed eradication of Ascariasis.

This review is done to briefly highlight the therapeutic options available for NAFLD (Non-Alcoholic Fatty Liver Disease), and the role of anti-oxidants in support of NAFLD. PubMed and Google Scholar search was done using the keywords such as NAFLD, Liver cirrhosis, fibrosis, steatosis, anti-oxidants, inflammatory markers, apoptosis. This review article contains precise data from a few crucial recent articles that throw light on the current situation and treatment options available for NAFLD patients. NAFLD was recently re-termed as MAFLD (Metabolic Associated fatty Liver Disease) and has started affecting a significant proportion of the population mainly due to the incidence of metabolic syndrome as one of the greatest risk factors of NAFLD. Therapeutic options for the same have been studied for a long time but no single effective option has been discovered yet. Understanding the mechanism of NAFLD has led to the use of vitamins especially vitamin E and other substances such as polyphenols which are the emerging new options included for the treatment. These targets the reactive oxygen species, inflammatory markers, modulate fatty acid oxidation, and insulin resistance. Recent guidelines have recommended the use of Vitamin E in biopsy-proven NAFLD patients without diabetes. On the contrary, vitamin E has side effects seen at certain doses due to which the therapeutic ability although most effective, is limited in such patients. Despite the risk profile, vitamin E is still considered one of the safest options due to patient tolerability and improvement in NAFLD stages that has been proven histologically as well but in non-diabetic patients. This article also provides a brief insight into other therapeutic options available in the category of nutrients. There is a need for research to look into more options available as treatment and also to identify the risk and benefits of vitamin E to find a more permanent therapeutic solution for NAFLD patients.

In recent years, clinical and animal studies have confirmed that metabolic associated fatty liver disease (MAFLD) is a multisystem disease. The extrahepatic complications of MAFLD, including cardiovascular disease, tumors, metabolic nephropathy, obstructive apnea syndrome, osteoporosis, psoriasis, iron overload, and various metabolic and endocrine diseases, are closely related. The incidence of these diseases is far higher than that of the liver disease itself. This article provides a comprehensive review of the correlation between MAFLD and psoriasis. Studies have shown that MAFLD is a common disease in adult patients with psoriasis. MAFLD is associated with a higher likelihood of developing metabolic syndrome and more severe skin disease in patients with psoriasis. In addition, patients with psoriasis are more likely to develop more severe MAFLD. However, further research is needed to clarify the biological mechanisms of MAFLD and psoriasis. Healthcare providers of patients with psoriasis should watch for the development of this liver disease. The coexistence of MAFLD should also be considered when planning treatment, because of the potential hepatotoxic effects of some conventional drugs for the treatment of psoriasis.

We report this unusual case of a one-day-old infant who presented with hematemesis and was found to have congenital duodenal web, The Diagnosis was made by Upper GI Imaging and Endoscopy and management was done by surgical repair. Congenital duodenal obstruction carries a risk of duodenitis in newborns, and they may present with acute hematemesis. The management includes early surgery to relieve the obstruction.

To assess clinicopathological characteristics of gastrointestinal stromal tumor (GIST) and the relationship between tumor necrosis factors and patient prognosis.

Data of 60 patients with gastric cancer (GC) admitted from September 2018 to April 2019 at the Hunan Provincial People's Hospital were collected. Clinicopathological characteristics were analyzed to assess the correlation between tumor necrosis factor and clinicopathological characteristics, immunohistochemical expression, and prognosis.

A difference was noted between tumor necrosis and tumor size, nucleosis imaging, NIH risk grade, and desmin in GC patients (P < 0.05), and between tumor necrosis and sex, age, site, and levels and immunohistochemical index of DOG-1, CD117, CD34, and SMA (P > 0.05).

There is a correlation between tumor necrosis and tumor size, nuclear division image, NIH risk grade, and desmin, and patients with GC have tumor necrosis and patient prognosis.

The leading cause of dementia is Alzheimer’s disease (AD), which affects millions worldwide. Aging populations can foretell the worsening burden of the disease in the future. AD is characterised by the following hallmark pathologies: amyloid-β over-production and deposition, abnormal hyperphosphorylation of tau leading to the formation of neurofibrillary tangles, and neuroinflammation. Many potential treatments fail in clinical trials, suggesting that present theories are outdated or lead to therapeutic dead-ends. A gum disease-causing species of bacteria, Porphyromonas gingivalis, is being increasingly linked with AD, given the ubiquity of gum disease amongst older populations, and studies have revealed that the bacteria causes and exacerbates AD pathology both in vitro and in vivo. P. gingivalis produce many neurotoxic molecules, including gingipain enzymes, lipopolysaccharide and phosphoglycerol dihydroceramides, and all of these have been shown to affect AD pathologies. Numerous mechanisms by which these neurotoxic species reach the brain have been proposed, and one of these is the bacteria’s use of outer membrane vesicles. This review presents the present evidence of the effects of P. gingivalis and its outer membrane vesicles, gingipains, lipopolysaccharide and phosphoglycerol dihydroceramides, on neurodegeneration in neuronal cultures, mice models and post-mortem studies, and determines how this evidence can be used to develop new treatments for AD.

Hepatocellular carcinoma (HCC) is listed as one of the most common causes of cancer-related death. Oncolytic therapy has become a promising treatment because of novel immunotherapies and gene editing technology, but biosafety concerns remain the biggest limitation for clinical application. We studied the the antitumor activity and biosafety of the wild-type Newcastle disease virus HK84 strain (NDV/HK84) and 10 other NDV strains.

Cell proliferation and apoptosis were determined by cell counting Kit-8 and fluorescein isothiocyanate Annexin V apoptosis assays. Colony formation, wound healing, and a xenograft mouse model were used to evaluate in vivo and in vitro oncolytic effectiveness. The safety of NDV/HK84 was tested in nude mice by an in vivo luciferase imaging system. The replication kinetics of NDV/HK84 in normal tissues and tumors were evaluated by infectious-dose assays in eggs. RNA sequencing analysis was performed to explore NDV/HK84 activity and was validated by quantitative real-time PCR.

The cell counting Kit-8 assays of viability found that the oncolytic activity of the NDV strains differed with the multiplicity of infection (MOI). At an MOI of 20, the oncolytic activity of all NDV strains except the DK/JX/21358/08 strain was >80%. The oncolytic activities of the NDV/HK84 and DK/JX/8224/04 strains were >80% at both MOI=20 and MOI=2. Only NDV/HK84 had >80% oncolytic activities at both MOI=20 and MOI=2. We chose NDV/HK84 as the candidate virus to test the oncolytic effect of NDV in HCC in the in vitro and in vivo experiments. NDV/HK84 killed human SK-HEP-1 HCC cells without affecting healthy cells.

Intratumor infection with NDV/HK84 strains compared with vehicle controls or positive controls indicated that NDV/HK84 strain specifically inhibited HCC without affecting healthy mice. High-throughput RNA sequencing showed that the oncolytic activity of NDV/HK84 was dependent on the activation of type I interferon signaling.

The percentage of vaccinated people in Ukraine and Israel extensively varies. Based on this large difference, the influence of possible collective immunity on the COVID-19 pandemic dynamics in summer 2021 was evaluated.

To clarify the presence of a natural collective immunity, the visible and actual characteristics of the COVID-19 epidemic in Ukraine were estimated based on the number of laboratory-confirmed cases (accumulated in May and June 2021), using a generalized SIR-model and parameter identification procedure, and considering the difference between registered and real number of cases.

The calculated optimal value of the visibility coefficient shows that most Ukrainians have already been infected with coronavirus, some of whom have been infected more than once. This suggests that Ukrainians have probably achieved a natural collective immunity. Despite the large percentage of fully vaccinated people in Israel (approximately 60%), the emergence of a new epidemic wave after June 15, 2021 was not prevented, and the number of deaths increased after July 5, 2021. A new wave of the pandemic in Ukraine after July 10, 2021 is characterized by a smaller daily number of new COVID-19 cases per capita and new deaths per capita, despite having a much lower number of vaccinated people than in Israel. This can be explained by a much lower level of testing (many cases in Ukraine remain undetected) and possibly by the probable natural immunity of Ukrainians.

High levels of vaccination and natural collective immunity are unlikely to prevent new waves of the COVID-19 pandemic caused by mutated coronavirus strains.