Thymic Carcinoma Presenting as a Mediastinal Mass Resembling a Cardiac Tumor.

Thymoma and thymic carcinomas are a few of the rarest malignancies seen in humankind. They are mostly seen in the Asian population, many of which are reported in the Southeast Asia region like Japan, China, Vietnam, etc. They usually can be a sequela of other underlying conditions such as myasthenia gravis or some unknown mutations that express later in life.   Our patient is a young 41-year-male, a healthy and active individual who presented for evaluation of acute shortness of breath, two months after recovering from SARS-CoV-19 infection. His shortness of breath progressed while on oxygen and diuretics, a Point of Care Ultrasound (POCUS) showed cardiac tamponade and moderate pleural effusion. A Computerized Tomographic (CT) scan of the chest/abdomen/pelvis showed cardiomegaly, pleural effusion, and a mass abutting the heart. A pericardiocentesis revealed malignant cells. Thymic carcinoma was confirmed with a core biopsy and the patient was initiated on treatment rapidly to help improve symptoms and contain the growing mass.  .

Deoxynivalenol Induces Drp-1-Mediated Mitochondrial Dysfunction via Elevating Oxidative Stress.

Mitochondrial dysfunction is often linked to neurotoxicity and neurological diseases and stems from oxidative stress, yet effective therapies are lacking. Deoxynivalenol (DON or vomitoxin) is one of the most common and hazardous type-B trichothecene mycotoxins, which contaminates crops used for food and animal feed. Despite the abundance of preliminary reports, comprehensive investigations are scarce to explore the relationship between these fungal metabolites and neurodegenerative disorders. The present study aimed to elucidate the precise role of DON in mitochondrial dynamics and cell death in neuronal cells. Excessive mitochondrial fission is associated with the pathology of several neurodegenerative diseases. Human SH-SY5Y cells were treated with different concentrations of DON (250-1000 ng/mL). Post 24 and 48 h DON treatment, the indexes were measured as follows: generation of reactive oxygen species (ROS), ATP levels, mitochondrial membrane potential, calcium levels, and cytotoxicity in SH-SY5Y cells. The results showed that cytotoxicity, intracellular calcium levels, and ROS in the DON-treated group increased, while the ATP levels and mitochondrial membrane potential decreased in a dose-dependent manner. With increasing DON concentrations, the expression levels of P-Drp-1, mitochondrial fission proteins Mff, and Fis-1 were elevated with reduced activities of MFN1, MFN2, and OPA1, further resulting in an increased expression of autophagic marker LC3 and beclin-1. The reciprocal relationship between mitochondrial damage and ROS generation is evident as ROS can instigate structural and functional deficiencies within the mitochondria. Consequently, the impaired mitochondria facilitate the release of ROS, thereby intensifying the cycle of damage and exacerbating the overall process. Using specific hydroxyl, superoxide inhibitors, and calcium chelators, our study confirmed that ROS and Ca2+-mediated signaling pathways played essential roles in DON-induced Drp1 phosphorylation. Therefore, ROS and mitochondrial fission inhibitors could provide critical research tools for drug development in mycotoxin-induced neurodegenerative diseases.

Nanocarrier - Mediated Salinomycin Delivery Induces Apoptosis and Alters EMT Phenomenon in Prostate Adenocarcinoma.

Salinomycin (Sal) has been recently discovered as a novel chemotherapeutic agent against various cancers including prostate cancer which is one of the most commonly diagnosed cancers affecting male populations worldwide. Herein we designed salinomycin nanocarrier (Sal-NPs) to extend its systemic circulation and to increase its anticancer potential. Prepared nanoform showed high encapsulation and sustained release profile for salinomycin. The present study elucidated the cytotoxicity and mechanism of apoptotic cell death of Sal-NPs against prostate cancer both in vitro and in vivo. At all measured concentrations, Sal-NPs showed more significant cytotoxicity to DU145 and PC3 cells than Sal alone. This effect was mediated by apoptosis, as confirmed by ROS generation, loss of MMP and cell cycle arrest at the G1 phase in both cells. Sal-NPs efficiently inhibited migration of PC3 and DU145 cells via effectively downregulating the epithelial mesenchymal transition. Also, the results confirmed that Sal-NPs can effectively inhibit the induction of Prostate adenocarcinoma in male Wistar rats. Sal-NPs treatment exhibited a decrease in tumour sizes, a reduction in prostate weight, and an increase in body weight, which suggests that Sal-NPs is more effective than salinomycin alone. Our results suggest that the molecular mechanism underlying the Sal-NPs anticancer effect may lead to the development of a potential therapeutic strategy for treating prostate adenocarcinoma.

COVID-19: Recent Insight in Genomic Feature, Pathogenesis, Immunological Biomarkers, Treatment Options and Clinical Updates on SARS-CoV-2.

SARS-CoV-2 is a highly contagious and transmissible viral infection that first emerged in 2019 and since then has sparked an epidemic of severe respiratory problems identified as "coronavirus disease 2019" (COVID-19) that causes a hazard to human life and safety. The virus developed mainly from bats. The current epidemic has presented a significant warning to life across the world by showing mutation. There are different tests available for testing Coronavirus, and RT-PCR is the best, giving more accurate results, but it is also time-consuming. There are different options available for treating n-CoV-19, which include medications such as Remdesivir, corticosteroids, plasma therapy, Dexamethasone therapy, etc. The development of vaccines such as BNT126b2, ChAdOX1, mRNA-1273 and BBIBP-CorV has provided great relief in dealing with the virus as they decreased the mortality rate. BNT126b2 and ChAdOX1 are two n-CoV vaccines found to be most effective in controlling the spread of infection. In the future, nanotechnology-based vaccines and immune engineering techniques can be helpful for further research on Coronavirus and treatment of this deadly virus. The existing knowledge about the existence of SARS-CoV-2, along with its variants, is summarized in this review. This review, based on recently published findings, presents the core genetics of COVID-19, including heritable characteristics, pathogenesis, immunological biomarkers, treatment options and clinical updates on the virus, along with patents.

Alcohol induces ER stress and apoptosis by inducing oxidative stress and disruption of calcium homeostasis in glial cells.

Alcohol has teratogenic effects that can cause developmental abnormalities and alter anatomical and functional characteristics of the developed brain and other organs. Glial cells play a crucial role in alcohol metabolism and protect neurons from toxic effects of alcohol. However, chronic alcohol exposure can lead to uncontrollable levels of reactive oxygen species, resulting in the death of glial cells and exposing neuronal cells to the toxic effects of alcohol. The exact molecular mechanism of alcohol-induced glial cell death has not been fully explored. This study reported that different concentrations of alcohol induce different expressions of ER stress markers in glial cells, focusing on the role of endoplasmic reticulum (ER) stress. Alcohol-induced concentration-dependent toxicity in both cells also induced oxidative stress, leading to mitochondrial damage. The expression of p53 and apoptotic proteins was significantly up-regulated after alcohol exposure, while Bcl2 (anti-apoptotic) was down-regulated. The signalling pathway for ER stress was activated and up-regulated marker proteins in a concentration-dependent manner. Cells pre-treated with BAPTA-AM and NAC showed significant resistance against alcohol assault compared to other cells. These in vitro findings will prove valuable for defining the mechanism by which alcohol modulates oxidative stress, mitochondrial and ER damage leading to glial cell death.

Pseudoexfoliative Deposits on an Intraocular Lens.

This case report discusses the finding of pseudoexfoliative material on the intraocular lens implant of a patient with a history of pseudoexfoliation syndrome and secondary glaucoma.

Biosensors - A Miraculous Detecting Tool in Combating the War against COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly known as COVID-19, created rack and ruin and erupted as a global epidemic. Nearly 482.3 million cases and approximately 6.1 million deaths have been reported. The World Health Organization (WHO) designated it an international medical emergency on January 30, 2020; shortly in March 2020, it was declared a pandemic. To address this situation, governments and scientists around the globe were urged to combat and prevent its spread, mainly when no treatment was available. Presently, quantitative real-time polymerase chain reaction (qRT-PCR) is the most widely utilized technique for diagnosing SARS-CoV-2. But this method is cumbersome, tedious, and might not be quickly accessible in isolated areas with a circumscribed budget. Therefore, there is a quest for novel diagnostic techniques which can diagnose the disease in a lesser time in an economical way. This paper outlines the potential of biosensors in the diagnosis of SARS-CoV-2. This review highlights the current state of presently available detection techniques, expected potential limits, and the benefits of biosensor-implicated tests against SARS-Cov-2 diagnosis. CRISPR-Cas9 implanted paper strip, field-effect transistor (FET) implanted sensor, nucleic-acid centric, aptamers-implanted biosensor, antigen-Au/Ag nanoparticles-based electrochemical biosensor, surface-enhanced Raman scattering (SERS)-based biosensor, Surface Plasmon Resonance, potential electrochemical biosensor, optical biosensor, as well as artificial intelligence (AI) are some of the novel biosensing devices that are being utilized in the prognosis of coronaviruses.

Overview of Advancement in Biosensing Technology, Including its Applications in Healthcare.

Clinical analysis necessitates using rapid and dependable diagnostic methodologies and approaches. Biomarkers may be an appropriate choice to fulfill this objective, as they are designed uncomplicated in use, specialized for the desired metabolite, susceptible to ongoing analysis and providing excellent outcomes, relatively affordable in the budget, and easily accessible. Biosensing devices are increasingly extensively utilized for treatment, and therefore a variety of applications such as prudence treatment and illness advancement surveillance, environment sensing, product standard, medicine development, toxicology, and scientific engineering. Biosensors can be developed using a wide variety of ways. Its combination with high-affinity macromolecules enables them to monitor a diverse variety of solutes in a specific as well as responsive manner. Enhanced sensing innovation leads to the detection of infection as well as the monitoring of people's reactions after treatment. Sensing tools are essential for a range of low and better implantable implants. Nanosensors offer a lot of prospects because they are simple, flexible, yet economical to develop. This article presents a detailed overview of breakthroughs in the subject and demonstrations of the variety of biosensors and the extension of nanoscience and nanotechnology methodologies that are applicable today.

Neuromyelitis optica spectrum disorder post-COVID-19 infection: A rare case report from Northeast India.

Multiple sclerosis and neuromyelitis optica spectrum disorder may be seen in the acute setting of coronavirus disease 2019 (COVID-19) infection or even post-recovery. Such patients may present with optic neuropathy along with weakness in the back and lower limbs. Ascending paralysis can present with respiratory distress in acute COVID-19 infection and may even prove to be fatal. We report a unique case of a 16-year-old female with past history of COVID-19 infection having optic neuropathy, and radioimaging showing demyelinating plaques in the central nervous system with spinal cord edema. Serology showed positivity for rheumatoid arthritis, and the patient was managed with steroids and rituximab.

Alcohol induced impairment/abnormalities in brain: Role of MicroRNAs.

Alcohol is a highly toxic substance and has teratogenic properties that can lead to a wide range of developmental disorders. Excessive use of alcohol can change the structural and functional aspects of developed brain and other organs. Which can further lead to significant health, social and economic implications in many countries of the world. Convincing evidence support the involvement of microRNAs (miRNAs) as important post-transcriptional regulators of gene expression in neurodevelopment and maintenance. They also show differential expression following an injury. MiRNAs are the special class of small non coding RNAs that can modify the gene by targeting the mRNA and fine tune the development of cells to organs. Numerous pieces of evidences have shown the relationship between miRNA, alcohol and brain damage. These studies also show how miRNA controls different cellular mechanisms involved in the development of alcohol use disorder. With the increasing number of research studies, the roles of miRNAs following alcohol-induced injury could help researchers to recognize alternative therapeutic methods to treat/cure alcohol-induced brain damage. The present review summarizes the available data and brings together the important miRNAs, that play a crucial role in alcohol-induced brain damage, which will help in better understanding complex mechanisms. Identifying these miRNAs will not only expand the current knowledge but can lead to the identification of better targets for the development of novel therapeutic interventions.

Incidental Finding of Right-Sided Idiopathic Spontaneous Acquired Diaphragmatic Hernia.

Spontaneous acquired diaphragmatic hernia is a rare finding which occurs in the absence of any trauma or surgery. Here, we present the case of an 83-year-old male who presented to the outpatient department complaining of nausea, vomiting, epigastric pain and sensation of fullness, loss of appetite, and occasional episodes of constipation, with no history of trauma or surgery. Clinical examination revealed no specific cause. A clinical diagnosis of cholelithiasis was initially suspected and confirmed by an ultrasound of the abdomen. However, considering the worsening of symptoms, a computed tomography scan revealed an incidental right-sided spontaneous diaphragmatic hernia. A subsequent laparoscopic surgery for cholecystectomy and the correction of the right-sided defect in the diaphragm was performed. spontaneous acquired diaphragmatic hernia occurring secondary to a defect on the right side of the diaphragm without any history of trauma or surgery is an extraordinary and infrequent radiological finding. Considering the challenging clinical diagnosis of such hernias, clinicians should be vigilant when patients exhibit worsening symptoms of nausea, vomiting, and gastrointestinal obstruction with or without respiratory and cardiac complications. The surgical management of such hernias is effective and secure and usually requires either an abdominal or thoracic approach and a combination of both accesses in some cases.

Piperine and Celecoxib synergistically inhibit colon cancer cell proliferation via modulating Wnt/ß-catenin signaling pathway.

BACKGROUND: Celecoxib (CXB), a selective COX-2 inhibitor NSAID, has exhibited prominent anti-proliferative potential against numerous cancers. However, its low bioavailability and long term exposure related cardiovascular side effects, limit its clinical application. In order to overcome these limitations, natural bioactive compounds with lower toxicity profile are used in combination with therapeutic drugs. Therfore, in this study Piperine (PIP), a natural chemo-preventive agent possessing drug bioavailability enhancing properties, was considered to be used in combination with low doses of CXB. PURPOSE: We hypothesized that the combination of PIP with CXB will have a synergistic anti-proliferative effect on colon cancer cells. STUDY DESIGN: The potency of PIP and CXB alone and in combination was evaluated in HT-29 human colon adenocarcinoma cells and mechanism of growth inhibition was investigated by analyzing the players in apoptotic and Wnt/ß-catenin signaling pathways. METHODS: The effect of PIP on the oral bioavailability of CXB in mice was investigated using HPLC analysis. The study investigated the synergistic anti-proliferative effect of CXB and PIP on HT-29 cells and IEC-6 non-tumorigenic rat intestinal epithelial cells by SRB cell viability assay. Further, the cellular and molecular mechanism(s) involved in the anti-proliferative combinatorial effect was extensively explored in HT-29 cells by flow cytometry and western blotting. The in vivo efficacy of this combination was studied in CT26.WT tumor syngeneic Balb/c mice model. RESULTS: PIP as a bioenhancer increased the oral bioavailability of CXB (129%). The IC50 of CXB and PIP were evaluated to select doses for combination treatment of HT-29 cells. The drug combinations having combination index (CI) less than 1 were screened using CompuSyn software. These combinations were significantly cytotoxic to HT-29 cells but IEC-6 were least effected. Further, the mechanism behind CXB and PIP mediated cell death was explored. The co-treatment led to reactive oxygen species generation, mitochondrial dysfunction, caspase activation and enhanced apoptosis in HT-29 cells. Additionally, the combination treatment synergistically modulated Wnt/ß-catenin pathway, downregulated the stemness markers and boosted therapeutic response in CT26 syngeneic Balb/c mice. CONCLUSION: The outcomes of the study suggests that combining CXB and PIP offers a novel approach for the treatment of colon cancer.

N-acetyl-cysteine in combination with celecoxib inhibits Deoxynivalenol induced skin tumor initiation via induction of autophagic pathways in swiss mice.

Deoxynivalenol is a trichothecene mycotoxin which naturally contaminates small grain, cereals intended for human and animal consumption. Investigations for dermal toxicity of DON has been needed and highlighted by WHO. Previous studies on dermal toxicity suggest that DON has DNA damaging potential leading to skin tumor initiation in mice skin. However, considering its toxicological manifestations arising after dermal exposure, strategies for its prevention/protection are barely available in literatute. Collectively, our study demonstrated that N-acetylcysteine (NAC), precursor of glutathione, significantly alters the genotoxic potential of DON. Further NAC in combination with Celecoxib (CXB) inhibits tumor growth by altering antioxidant status and increasing autophagy in DON initiated Swiss mice. Despite the broad spectrum use of CXB, its use is limited by the concerns about its adverse effects on the cardiovascular system. Serum parameters and histology analysis revealed that CXB (2 mg) when applied topically for 24 weeks did not impart any cardiovascular toxicity which could be because skin permeation potential of CXB was quite low when analyzed through HPLC analysis. Although the anticancer effects of CXB and NAC have been studied, however, the combination of NAC and CXB has yet not been explored for any cancer treatment. Therefore our observations provide additional insights into the therapeutic effects of combinatorial treatment of CXB and NAC against skin tumor prevention. This approach might form a novel alternative strategy for skin cancer treatment as well as skin associated toxicities caused by mycotoxins such as DON. This combinatorial approach can overcome the limitations associated with the use of CXB for long term as topical application of the same seems to be safe in comparison to the oral mode of administration.

Celecoxib reduces Deoxynivalenol induced proliferation, inflammation and protein kinase C translocation via modulating downstream targets in mouse skin.

Exposure to mycotoxins is mostly by ingestion but also occurs by the dermal and inhalation routes. The present study for the first time demonstrated that mycotoxin Deoxynivalenol (DON), permeates through Swiss albino mice skin, which demands awareness of health risks in people who are dermally exposed to mycotoxins especially agricultural farmers. Despite the widespread contamination of DON in food commodities studies to alleviate DON's toxicity are sparsely reported. Thus effective measures to combat mycotoxins associated toxicity remains an imperative aspect to be considered from the angle of dermal exposure. Topical application of Celecoxib (1-2 mg), followed by DON (100 µg) application on the dorsal side of mice, resulted in substantial decrease in DON-induced (i) edema, hyperplasia, cell proliferation (ii) inhibition of cytokine and prostaglandin-E2 levels (iii) phosphorylation of ERK1/2, JNK, p38, MAPKKs, CREB, P90-RSK (iv) downregulation of c-Jun, c- Fos, phospho-NF-kB and their downstream target proteins cyclin D1 and COX-2. Using Ro-31-8220 (Protein-Kinase-C inhibitor), it was observed PKC was responsible for DON induced upregulation of COX-2 and iNOS proteins. Treatment of Celecoxib decreased DON-induced translocation of Protein Kinase C isozymes (α,ε,γ), demonstrating the role of PKC in DON-mediated biochemical and molecular alterations responsible for its dermal toxicity. The present findings indicate that topical application of celecoxib is effective in the management of inflammatory skin disorders induced by foodborne fungal toxin DON. The skin permeation potential of Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor NSAID, was also assessed, and the results indicated that the permeation was relatively lower as compared to the oral mode of administration. Hence topical use of celecoxib may be preferred over oral dosing because of lower systemic absorption and to avoid the unwanted side effects. This study provides a prospect for exploring the clinical efficacy of topically applied COX-2 inhibitors for the management of inflammatory skin disorders induced by foodborne fungal toxins.