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Current State of Human Gene Therapy: Approved Products and Vectors.

In the realm of gene therapy, a pivotal moment arrived with Paul Berg's groundbreaking identification of the first recombinant DNA in 1972. This achievement set the stage for future breakthroughs. Conditions once considered undefeatable, like melanoma, pancreatic cancer, and a host of other ailments, are now being addressed at their root cause-the genetic level. Presently, the gene therapy landscape stands adorned with 22 approved in vivo and ex vivo products, including IMLYGIC, LUXTURNA, Zolgensma, Spinraza, Patisiran, and many more. In this comprehensive exploration, we delve into a rich ass

Prevalence and risk factors of intra-dialytic hypotension: a 5 year retrospective report from a single Nigerian Centre.

IntroductionIntra-dialytic hypotension (IDH) is a common complication of haemodialysis that impacts negatively on the patient's quality of life and can induce serious cardiovascular events.MethodsRecords of all adults who had haemodialysis treatments from Jan 2012-Jan 2016 were reviewed. Socio-demographic data, health status of patient, aetiology of renal disease, clinical and biochemical parameters such as systolic and diastolic blood pressures (SBP and DBP), packed cell volume, were collated using Microsoft Excel.ResultsThe overall prevalence of intra-dialytic hypotension was 8.6%. Of all ha

Cobalamin deficiency, hyperhomocysteinemia, and dementia.

IntroductionAlthough consensus guidelines recommend checking serum B12 in patients with dementia, clinicians are often faced with various questions: (1) Which patients should be tested? (2) What test should be ordered? (3) How are inferences made from such testing? (4) In addition to serum B12, should other tests be ordered? (5) Is B12 deficiency compatible with dementia of the Alzheimer's type? (6) What is to be expected from treatment? (7) How is B12 deficiency treated?MethodsOn January 31st, 2009, a Medline search was performed revealing 1,627 citations related to cobalamin deficiency, hype

Chimeric antigen receptor T cell: A cancer immunotherapy.

During present decade, targeted drug therapy has been the epitome for treatment of cancer. Drugs like Imatinib, a tyrosine kinase receptor inhibitor and Trastuzumab, an human epidermal growth factor receptor-2/neu inhibitor, has been developed and accepted widely for management of chronic myeloid leukaemia and breast cancer respectively. Recent development among the various immunotherapies is adoptive cell transfer (ACT). Research on development of various types of ACT immunotherapy is going on, but so far, Chimeric antigen receptors T cell therapy (CAR-T) has achieved the maximum advancement

Immune Dysfunction in Uremia 2020.

Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failur

Cyclic Peptides in Modern Drug Discovery: Trends and Therapeutic Directions.

Peptide therapeutics are an important drug modality due to their high specificity, favorable safety, and expanding design potential. Among them, cyclic peptides occupy a space between small molecules and biologics, offering improved rigidity, stability, and target engagement. This report analyzes trends in cyclic peptide research using data from the CAS Content Collection over the past two decades. Results show a steady rise in academic publications and patents, reflecting growing interest across discovery and development. Notably, oral administration is gaining attention, indicating progress

Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects.

The prognosis of patients with systemic lupus erythematosus has greatly improved since treatment regimens combining corticosteroids and immunosuppressive medications have been widely adopted in therapeutic strategies given to these patients. Immune suppression is evidently efficient but also leads to higher susceptibility to infectious and malignant diseases. Toxic effects and sometimes unexpectedly dramatic complications of current therapies have been progressively reported. Identifying novel molecular targets therefore remains an important issue in the treatment of lupus. The aim of this rev

Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies.

The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making dia

Protective Effects of Flavonoids Against Mitochondriopathies and Associated Pathologies: Focus on the Predictive Approach and Personalized Prevention.

Multi-factorial mitochondrial damage exhibits a "vicious circle" that leads to a progression of mitochondrial dysfunction and multi-organ adverse effects. Mitochondrial impairments (mitochondriopathies) are associated with severe pathologies including but not restricted to cancers, cardiovascular diseases, and neurodegeneration. However, the type and level of cascading pathologies are highly individual. Consequently, patient stratification, risk assessment, and mitigating measures are instrumental for cost-effective individualized protection. Therefore, the paradigm shift from reactive to pred

Acute Kidney Injury Associated with Anticancer Therapies: Small Molecules and Targeted Therapies.

Molecular targeted therapy has revolutionized cancer treatment by significantly improving patient survival compared with standard conventional chemotherapies. The use of these drugs targets specific molecules or targets, which block growth and spread of cancer cells. Many of these therapies have been approved for use with remarkable success in breast, blood, colorectal, lung, and ovarian cancers. The advantage over conventional chemotherapy is its ability to deliver drugs effectively with high specificity while being less toxic. Although known as "targeted," many of these agents lack specifici

Emerging Roles of Mesenchymal Stem/Stromal-Cell-Derived Extracellular Vesicles in Cancer Therapy.

Despite the tremendous efforts of many researchers and clinicians, cancer remains the second leading cause of mortality worldwide. Mesenchymal stem/stromal cells (MSCs) are multipotent cells residing in numerous human tissues and presenting unique biological properties, such as low immunogenicity, powerful immunomodulatory and immunosuppressive capabilities, and, in particular, homing abilities. Therapeutic functions of MSCs are mediated mostly by the paracrine effect of released functional molecules and other variable components, and among them the MSC-derived extracellular vesicles (MSC-EVs)

Infection related membranoproliferative glomerulonephritis secondary to anaplasmosis: A case report.

BACKGROUND: Anaplasmosis is a tick-borne disease with a range of clinical manifestations, from a flu-like illness with fever and myalgias to a severe systemic disease with multisystem organ failure. Although renal involvement is not a common presentation, there have been few cases reporting acute kidney injury from Anaplasmosis. CASE SUMMARY: We present a 55-year-old female with anaplasmosis who developed acute kidney injury due to membranoproliferative glomerulonephritis (MPGN). The patient originally presented with cough and shortness of breath. She was admitted to the hospital with a diagn

Pamidronate-induced irreversible symptomatic hypocalcemia in a dog with hypercalcemia after glucocorticoid withdrawal: a case report.

BACKGROUND: Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog. CASE PRESENTATION: An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia.

Exosomes: A new option for osteoporosis treatment.

Osteoporosis is a systemic bone disease characterized by reduced bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture. However, the pathogenesis and molecular mechanisms of this disease remain unclear. Extracellular vesicles, structures originating from the plasma membrane and ranging from 30 nm to 5 µm in diameter, play an important role in intercellular communication in the bone microenvironment. Exosomes are extracellular vesicles that deliver cargo molecules, including endogenous proteins, lipids and nucleic acids. These ca

Cancer and Exercise: Warburg Hypothesis, Tumour Metabolism and High-Intensity Anaerobic Exercise.

There is ample evidence that regular moderate to vigorous aerobic physical activity is related to a reduced risk for various forms of cancer to suggest a causal relationship. Exercise is associated with positive changes in fitness, body composition, and physical functioning as well as in patient-reported outcomes such as fatigue, sleep quality, or health-related quality of life. Emerging evidence indicates that exercise may also be directly linked to the control of tumour biology through direct effects on tumour-intrinsic factors. Beside a multitude of effects of exercise on the human body, on

The role of CD38 in HIV infection.

The widely-expressed molecule CD38 is a single-stranded type II transmembrane glycoprotein that is mainly involved in regulating the differentiation and activation state of the cell. CD38 has broad and complex functions, including enzymatic activity, intercellular signal transduction, cell activation, cytokine production, receptor function and adhesion activity, and it plays an important role in the physiological and pathological processes of many diseases. Many studies have shown that CD38 is related to the occurrence and development of HIV infection, and CD38 may regulate its progression thr

Emergency Care

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… Fluid therapy The diagnosis of intracellular fluid deficit is difficult and is based more on the presence of hypernatremia or hyperosmolality than on clinical signs. … An intracellular fluid deficit is expected when free water loss from insensible losses and vomiting, diarrhea, or urine is not matched by free water intake. …

Current Challenges in Chimeric Antigen Receptor T-cell Therapy in Patients With B-cell Lymphoid Malignancies.

Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy based on genetically engineered T cells derived from patients. The introduction of CAR T-cell therapy has changed the treatment paradigm of patients with B-cell lymphoid malignancies. However, challenging issues including managing life-threatening toxicities related to CAR T-cell infusion and resistance to CAR T-cell therapy, leading to progression or relapse, remain. This review summarizes the issues with currently approved CAR T-cell therapies for patients with relapsed or refractory B-cell lymphoid malignancies, inc

Роль окситоцина и Васопрессина в нейропсихиатрических расстройствах: терапевтический потенциал агонистов и антагонистов.

Окситоцин (OT) и вазопрессин (AVP) являются гипоталамическими нейропептидами, которые традиционно ассоциируются с их регулирующей ролью в размножении, гомеостазисе воды и социальном поведении. Интересно, что в последние годы эта роль расширилась и эти нейропептиды стали лечебными мишенями для различных нейропсихиатрических заболеваний, таких, как аутизм, зависимость, шизофрения, депрессия и тревожное расстройство. В связи с химическими и физическими характеристиками этих нейропептидов, включая короткий период полураспада, плохое проникновение через мозговые барьеры, беспорядочность для AVP и O

MicroRNAs - novel biomarkers for malignant pleural effusions.

Lung cancer is one of the most common causes of cancer death. Its poor prognosis can be attributed to the patients' advanced or metastatic presentation at the time of diagnosis. To improve and accelerate the diagnosis, better therapeutic and diagnostic methods are constantly being sought. MicroRNAs (miRNAs) are short nucleotide sequences of single-stranded, non-coding RNA that function as critical post-transcriptional regulators of gene expression. They are identified not only intracellularly, but also in physiological and pathological body fluids. These molecules are responsible for the regul