Reduction of tumor necrosis factor (TNF) in milk of women receiving anti-TNF antibody.

Background: Tumor Necrosis Factor (TNF) are expressed in milk. Experimental data indicate enhanced brain growth and cognitive development in the mouse offspring given milk deficient in TNF and TNF-dependent chemokines. Although monoclonal antibodies against TNF (TNFmAb) are used during breastfeeding due to minimal milk excretion, whether it affects endogenous TNF levels in human milk is unclear.

Ecto-CD38-NADase inhibition modulates cardiac metabolism and protects mice against doxorubicin-induced cardiotoxicity.

Aims: Doxorubicin (DXR) is a chemotherapeutic agent that causes dose-dependent cardiotoxicity. Recently, it has been proposed that the NADase CD38 may play a role in doxorubicin-induced cardiotoxicity (DIC). CD38 is the main NAD+-catabolizing enzyme in mammalian tissues.

Yoga Intervention Improves the Metabolic Parameters and Quality of Life among Infertile Women with Polycystic Ovary Syndrome in Indian Population.

Background: The heterogenic manifestations of polycystic ovarian syndrome have led to various treatment approaches that include improving hormonal imbalance, weight management, and improving quality of life (QoL). Yoga therapy being a versatile treatment approach benefits physical and mental well-being and can be recommended to women with polycystic ovary syndrome (PCOS).

Objective: The objective of this study was to study the effect of structured yoga intervention on anthropometric, metabolic, hormonal, biochemical, ovarian morphology, and infertility-related QoL parameters among infertile women with PCOS.

Heavy-chain antibody targeting of CD38 NAD hydrolase ectoenzyme to prevent fibrosis in multiple organs.

The functionally pleiotropic ectoenzyme CD38 is a glycohydrolase widely expressed on immune and non-hematopoietic cells. By converting NAD to ADP-ribose and nicotinamide, CD38 governs organismal NAD homeostasis and the activity of NAD-dependent cellular enzymes. CD38 has emerged as a major driver of age-related NAD decline underlying adverse metabolic states, frailty and reduced health span.

Mottling in Septic Shock: Ethnicity and Skin Color Matter.

Background: Skin mottling as a clinical perfusion marker in septic shock is significantly associated with severity and outcome in white-skinned population and its validity as a clinical sign in dark-skinned population is not known. The objectives of this study were to evaluate mottling in septic shock in the Indian ethnic population who has different skin color as compared to the white-skinned population and to assess mottling as an outcome predictor with capillary refill time (CRT) and other biochemical parameters which are the established clinical markers of perfusion in septic shock.

Materials And Methods: We conducted a prospective observational study of patients with skin color categories 21-34 on the von Luschan scale or Fitzprick type IV-VI who had septic shock needing a high dose of norepinephrine ≥0.

Successful combined umbilical cord blood and bone marrow transplantation from an HLA-matched sibling for MPS VI: a case report.

Unlabelled: Mucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy syndrome, polydystrophic dwarfism, and arysulfatase B (ASB) deficiency, is a lysosomal storage disorder with autosomal recessive inheritance characterized by progressive multisystem involved that causes many tissues and organs to enlarge and become inflamed. Skeletal deformities are common that progress and worsen in varying degrees thus affecting quality of life and life expectancy. Many studies have shown that allogeneic hematopoietic stem cell transplantation can reduce morbidity and enhance the survival and quality of life in such patients.

Oncogenic role and target properties of the lysine-specific demethylase KDM1A in chronic lymphocytic leukemia.

In chronic lymphocytic leukemia (CLL), epigenetic alterations are considered to centrally shape the transcriptional signatures that drive disease evolution and underlie its biological and clinical subsets. Characterizations of epigenetic regulators, particularly histone-modifying enzymes, are very rudimentary in CLL. In efforts to establish effectors of the CLL-associated oncogene T-cell leukemia 1A (TCL1A), we identified here the lysine-specific histone demethylase KDM1A to interact with the TCL1A protein in B cells in conjunction with an increased catalytic activity of KDM1A.

Diagnosis of Coronavirus Disease From Chest X-Ray Images Using DenseNet-169 Architecture.

The coronavirus disease (COVID-19) is a very contagious and dangerous disease that affects the human respiratory system. Early detection of this disease is very crucial to contain the further spread of the virus. In this paper, we proposed a methodology using DenseNet-169 architecture for diagnosing the disease from chest X-ray images of the patients.

A T-cell engaging bispecific antibody with a tumor-selective bivalent folate receptor alpha binding arm for the treatment of ovarian cancer.

The use of T-cell engagers (TCEs) to treat solid tumors is challenging, and several have been limited by narrow therapeutic windows due to substantial on-target, off-tumor toxicities due to the expression of low levels of target antigens on healthy tissues. Here, we describe TNB-928B, a fully human TCE that has a bivalent binding arm for folate receptor alpha (FRα) to selectively target FRα overexpressing tumor cells while avoiding the lysis of cells with low levels of FRα expression. The bivalent design of the FRα binding arm confers tumor selectivity due to low-affinity but high-avidity binding to high FRα antigen density cells.

TNB-738, a biparatopic antibody, boosts intracellular NAD+ by inhibiting CD38 ecto-enzyme activity.

Cluster of differentiation 38 (CD38) is an ecto-enzyme expressed primarily on immune cells that metabolize nicotinamide adenine dinucleotide (NAD+) to adenosine diphosphate ribose or cyclic ADP-ribose and nicotinamide. Other substrates of CD38 include nicotinamide adenine dinucleotide phosphate and nicotinamide mononucleotide, a critical NAD+ precursor in the salvage pathway. NAD+ is an important coenzyme involved in several metabolic pathways and is a required cofactor for the function of sirtuins (SIRTs) and poly (adenosine diphosphate-ribose) polymerases.

Transcriptome analysis reveals upregulation of immune response pathways at the invasive tumour front of metastatic seminoma germ cell tumours.

Background: Testicular germ cell tumours (TGCTs) have a high metastasis rate. However, the mechanisms related to their invasion, progression and metastasis are unclear. Therefore, we investigated gene expression changes that might be linked to metastasis in seminomatous testicular germ cell tumour (STGCT) patients.

Hypothalamic miR-1983 Targets Insulin Receptor β and the Insulin-mediated miR-1983 Increase Is Blocked by Metformin.

MicroRNAs (miRNAs) expressed in the hypothalamus are capable of regulating energy balance and peripheral metabolism by inhibiting translation of target messenger RNAs (mRNAs). Hypothalamic insulin resistance is known to precede that in the periphery, thus a critical unanswered question is whether central insulin resistance creates a specific hypothalamic miRNA signature that can be identified and targeted. Here we show that miR-1983, a unique miRNA, is upregulated in vitro in 2 insulin-resistant immortalized hypothalamic neuronal neuropeptide Y-expressing models, and in vivo in hyperinsulinemic mice, with a concomitant decrease of insulin receptor β subunit protein, a target of miR-1983.

Intravenous Methylene Blue as a Rescue Therapy in the Management of Refractory Hypoxia in COVID-19 ARDS Patients: A Case Series.

To describe the clinical outcomes of hypoxic coronavirus disease 2019 (COVID-19) patients treated with intravenous methylene blue (MB) in a tertiary care hospital. We conducted a case series of 50 patients with hypoxic COVID-19 treated with intravenous MB admitted to our hospital between June 01 and September 10, 2020. Intravenous MB was administered as rescue therapy in dosage of 1 mg/kg body weight, with a maximum of five doses, to patients with high oxygen requirements (SpO/FiO <200) apart from the standard of care after obtaining G6PD levels.

Immunofluorescence of GFAP and TNF-α in the Mouse Hypothalamus.

Immunofluorescence is a reliable method for identifying specific proteins in neuronal and glial cell populations of the hypothalamus. Several immunofluorescence protocols are available to detect protein markers and neuropeptides in the hypothalamus; however, published methods may vary in subtle details that can potentially impact the final outcome of the procedure. Here, we provide a detailed protocol suitable for thin cryostat sections, which has been successful for specific antibodies directed against key markers of hypothalamic neurons and glial cells.

Attenuating CD3 affinity in a PSMAxCD3 bispecific antibody enables killing of prostate tumor cells with reduced cytokine release.

Background: Therapeutic options currently available for metastatic castration-resistant prostate cancer (mCRPC) do not extend median overall survival >6 months. Therefore, the development of novel and effective therapies for mCRPC represents an urgent medical need. T cell engagers (TCEs) have emerged as a promising approach for the treatment of mCRPC due to their targeted mechanism of action.

A Retrospective Observational Study of Hypoxic COVID-19 Patients Treated with Immunomodulatory Drugs in a Tertiary Care Hospital.

Objectives: To describe the demographics and evaluate the clinical outcomes of hypoxic coronavirus disease-2019 (COVID-19) patients treated with different immunomodulatory (IM) drugs in a resource-limited setting.

Materials And Methods: We conducted a retrospective cohort study of these patients admitted to our hospital between March 22 and May 31, 2020. Data were abstracted from multiple electronic data sources or patient charts to provide information on patient characteristics, clinical, laboratory variables, and outcomes.

Insulin signalling in hypothalamic neurones.

Subsequent to the discovery of insulin by Banting and Best in the Department of Physiology at the University of Toronto 100 years ago, the field of insulin signalling and action has grown at a remarkable pace. Yet, the recognition that insulin action in the brain is critical for whole body homeostasis has only recently been appreciated. The hypothalamus is a key region in the brain that responds to circulating insulin by engaging a complex signalling cascade resulting in the ultimate release of neuropeptides that control hunger and feeding.

Expression profiling on subclasses of primary parotid gland carcinomas.

Introduction: The underlying molecular mechanisms of parotid gland carcinomas (PGC) are still unknown. Knowledge about the tumor-driving signaling pathways is necessary either for diagnostics or developing new therapeutic options in this heterogeneous and rare entity.

Material And Methods: 94 matching RNA formalin-fixed and paraffin-embedded tissue samples from PGC and the corresponding non-tumor area, RNA quality and quantity were sufficient for gene expression profiling of 770 genes using the NanoString's nCounter technology.

Single Cell Sequencing: A New Dimension in Cancer Diagnosis and Treatment.

Cancer is one of the leading causes of death worldwide and well known for its complexity. Cancer cells within the same tumor or from different tumors are highly heterogeneous. Furthermore, stromal and immune cells within tumor microenvironment interact with cancer cells to play important roles in how tumors progress and respond to different treatments.

A case report: An aortobifemoral bypass implant found during cadaver dissection promotes inquiry-based learning.

Introduction: An unusual vascular implant found during routine cadaver dissection influenced instructors and students to learn more about the underlying disease and the surgical technique used to treat this disorder triggering an inquiry-based learning.

Presentation Of Case: This report describes a case of peripheral arterial disease (PAD) with an aortobifemoral arterial bypass implant that was never found before in any of the previously dissected cadavers at Gannon University.

Discussion: PAD develops due to impaired blood flow to the lower extremities that causes numbness, weakness, and lower leg pain.

Resveratrol Inhibits Neointimal Growth after Arterial Injury in High-Fat-Fed Rodents: The Roles of SIRT1 and AMPK.

We have shown that both insulin and resveratrol (RSV) decrease neointimal hyperplasia in chow-fed rodents via mechanisms that are in part overlapping and involve the activation of endothelial nitric oxide synthase (eNOS). However, this vasculoprotective effect of insulin is abolished in high-fat-fed insulin-resistant rats. Since RSV, in addition to increasing insulin sensitivity, can activate eNOS via pathways that are independent of insulin signaling, such as the activation of sirtuin 1 (SIRT1) and AMP-activated kinase (AMPK), we speculated that unlike insulin, the vasculoprotective effect of RSV would be retained in high-fat-fed rats.

Why Does Knocking Out NACHO, But Not RIC3, Completely Block Expression of α7 Nicotinic Receptors in Mouse Brain?

Alpha7 nicotinic acetylcholine receptors (α7nAChRs) are interesting not only because of their physiological effects, but because this receptor requires chaperones to traffic to cell surfaces (measured by alpha-bungarotoxin [αBGT] binding). While knockout (KO) animals and antibodies that react across species exist for encoding the protein chaperone NACHO, commercially available antibodies against the chaperone RIC3 that allow Western blots across species have not been generally available. Further, no effects of deleting RIC3 function ( KO) on α7nAChR expression are reported.

Yoga: Can it be integrated with treatment of neuropathic pain?

Background: Neuropathic pain (NP) is a debilitating condition that may result from spinal cord injury (SCI). Nearly 75% of all SCI results in NP affecting 17,000 new individuals in the United States every year, and an estimated 7-10% of people worldwide. It is caused by damaged or dysfunctional nerve fibers sending aberrant signals to pain centers in the central nervous system causing severe pain that affects daily life and routine.