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The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy-Drug Repurposing.

p53 and p73 are critical tumor suppressors that are often inactivated in human cancers through various mechanisms. Owing to their high structural homology, the proteins have many joined functions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53 is known as the 'guardian of the genome' and together with p73 forms a barrier against cancer development and progression. The TP53 is mutated in more than 50% of all human cancers and the germline mutations in TP53 predispose to the early onset of multiple tumors in Li-Fraumeni syndrome (LFS), the inherited cance

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… Panhematin ® , applied in clinics to treat acute attacks in porphyria, was recently repurposed to inhibit the metastatic spread of lung tumors in mouse model. … The action spectrum for skin lesions in porphyria cutanea tarda. Lancet. 1959;273:912–914. doi: 10.1016/S0140-6736(59)91311-X. 129. Cheruvu S., Sacher R.A. Pathobiology of Human Disease. Elsevier Inc.; Amsterdam, The Netherlands: 2014. The Porphyrias and Sideroblastic Anemias. 130. …

Редактор: Серия публикаций Сообщества: клинические и генетические детерминанты диабета и осложнений, том II.

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Acute hepatic encephalopathy presenting as cortical laminar necrosis: case report.

We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest th

Chemistry and Pharmacology of Fluorinated Drugs Approved by the FDA (2016-2022).

Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding a

Protecting Frontline Health Care Workers from COVID-19 with Hydroxychloroquine Pre-exposure Prophylaxis: A structured summary of a study protocol for a randomised placebo-controlled multisite trial in Toronto, Canada.

OBJECTIVES: Primary Objective: To determine if pre-exposure prophylaxis (PrEP) with 400mg hydroxychloroquine (HCQ), taken orally once daily reduces microbiologically confirmed COVID-19 among front line health care workers at high risk for SARS-CoV-2 exposure. Secondary Objectives: To compare the following between study arms: adverse events; symptomatic COVID-19; duration of symptomatic COVID-19; days hospitalized attributed to COVID-19; respiratory failure attributable to COVID-19 requiring i) non-invasive ventilation or ii) intubation/mechanical ventilation; mortality attributed to COVID-19,

Proactive Prophylaxis With Azithromycin and HydroxyChloroquine in Hospitalised Patients With COVID-19 (ProPAC-COVID): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The aim of this randomised GCP-controlled trial is to clarify whether combination therapy with the antibiotic azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy and pre-emptive treatment of supra-infections can shorten hospitalisation duration for patients with COVID-19 (measured as "days alive and out of hospital" as the primary outcome), reduce the risk of non- invasive ventilation, treatment in the intensive care unit and death. TRIAL DESIGN: This is a multi-centre, randomised, Placebo-controlled, 2-arm ratio 1:1, parallel group doub

Sustained virologic response improved the long-term health-related quality of life in patients with chronic hepatitis C: a prospective national study in China.

BACKGROUND: To investigate the trends in health-related quality of life (HRQoL) among hepatitis C virus (HCV) patients and to assess the longitudinal impact of antiviral therapy on their well-being. METHODS: In this prospective multicenter observational study in adults with HCV infection, sociodemographic, clinical characteristics and EQ-5D questionnaires were collected. Generalized estimating equation (GEE) models were used to assess the associations between these variables and changes in HRQoL over time. RESULTS: 456 patients were included, with a median age of 46.5 (36.5-57.0) years, of w

RNA therapeutics in targeting G protein-coupled receptors: Recent advances and challenges.

G protein-coupled receptors (GPCRs) are the major targets of existing drugs for a plethora of human diseases and dominate the pharmaceutical market. However, over 50% of the GPCRs remain undruggable. To pursue a breakthrough and overcome this situation, there is significant clinical research for developing RNA-based drugs specifically targeting GPCRs, but none has been approved so far. RNA therapeutics represent a unique and promising approach to selectively targeting previously undruggable targets, including undruggable GPCRs. However, the development of RNA therapeutics faces significant cha

Natural and semisynthetic candidate molecules for COVID-19 prophylaxis and treatment.

Coronaviruses (CoVs) represent a family of viruses that have numerous animal hosts, and they cause severe respiratory, as well as systemic and enteric infections, in humans. Currently, there are limited antiviral strategies for treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The lack of specific antiviral medicines and SARS-CoV-2 vaccines continues to aggravate the situation. Natural product-based antiviral drugs have been used in the two previous CoV outbreaks: Middle East respiratory syndrome coronavirus (MERS-CoV) and the first SARS-CoV. This re

Grzybowski's Generalized Eruptive Keratoacanthomas in a Patient with Terminal Kidney Disease-An Unmet Medical Need Equally Ameliorated by Topical Imiquimod Cream and Lapacho Tea Wraps: A Case Report.

IntroductionDevelopment of singular keratoacanthoma (KA) is generally considered a benign condition as it has a tendency to regress spontaneously in spite of histological similarity to squamous cell carcinoma. Most KAs undergo excision to rule out differential diagnoses. Several alternative treatment modalities (keratinolytic, ablative, immunomodulating, antiproliferative, or targeted therapy) have been described in the past with varying success, underlining the therapeutic challenges associated with large or multiple lesions. Isomorphic response (Koebner phenomenon) may limit the efficacy of

Diabetes mellitus and the skin.

Several dermatoses are routinely associated with diabetes mellitus, especially in patients with chronic disease. This relationship can be easily proven in some skin disorders, but it is not so clear in others. Dermatoses such necrobiosis lipoidica, granuloma annulare, acanthosis nigricans and others are discussed in this text, with an emphasis on proven link with the diabetes or not, disease identification and treatment strategy used to control those dermatoses and diabetes.

A cross-sectional assessment of health-related quality of life in Chinese patients with chronic hepatitis c virus infection with EQ-5D.

BackgroundHepatitis C virus (HCV) infection is one of the most common liver infections, with a decrement in HRQoL of HCV patients. This study aims to assess Health-related quality of life (HRQoL) in Chinese patients with chronic HCV infection, and to identify significant predictors of the HRQoL in these patients of China.MethodsIn this cross-sectional observational study, treatment-naïve Han ethnic adults with chronic HCV infection were enrolled. Adopting European Quality of Life scale (EQ-5D) and EuroQOL visual analogue scale (EQ-VAS) were used to qualify HRQoL. Results were reported in descr

Grover's Disease in a Kidney Transplant Recipient.

Dear Editor, It is not unusual for patients with renal insufficiency to develop skin pathologies. There are reports in the literature of increased incidence of calciphylaxis, pruritus, perforating dermatoses, and porphyria cutanea tarda in this patient population (1). Although it is quite rare, Grover's disease (GD) has been reported in several patients with renal insufficiency, but only once in a renal transplant recipient (2). The disease follows three patterns: persistently pruritic, transient eruptive, or a chronic asymptomatic course (3). Common risk factors concomitant with disease preva

Стрессивая симметрия: паралич двустороннего Белла, потенциально вызванный экстремальным стрессом.

Лица с нервыми (FNP) идиопатического происхождения обычно называются параличом Белла. Двусторонний ФНП представляет собой исключительно редкую подгруппу всех дел, связанных с параличом Белла. Она может проявляться либо синхронно, либо последовательно, с одной стороны, с другой стороны, с последующим участием противоположной стороны в течение первых 30 дней с момента возникновения симптома. Обычные этиологии ФНП охватывают такие инфекции, как инфекционный мононуклеоз, грипп, болезнь лайма и менингит. Неинфекционные причины включают в себя новообразования, множественный склероз и синдром Гильен-

Clinical practice guidelines on addressing cognitive impairment in treatable dementias.

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Current Advances in RNA Therapeutics for Human Diseases.

Following the discovery of nucleic acids by Friedrich Miescher in 1868, DNA and RNA were recognized as the genetic code containing the necessary information for proper cell functioning. In the years following these discoveries, vast knowledge of the seemingly endless roles of RNA have become better understood. Additionally, many new types of RNAs were discovered that seemed to have no coding properties (non-coding RNAs), such as microRNAs (miRNAs). The discovery of these new RNAs created a new avenue for treating various human diseases. However, RNA is relatively unstable and is degraded fairl

Home Treatment of Older People with Symptomatic SARS-CoV-2 Infection (COVID-19): A structured Summary of a Study Protocol for a Multi-Arm Multi-Stage (MAMS) Randomized Trial to Evaluate the Efficacy and Tolerability of Several Experimental Treatments to Reduce the Risk of Hospitalisation or Death in outpatients aged 65 years or older (COVERAGE trial).

OBJECTIVES: To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation. TRIAL DESIGN: Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Participants will be randomly allocated 1:1:1:1:1 to the following strategies: Arm 1: Control arm Arms 2 to 5: Experimental treatment arms Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and S

Brazilian Academy of Neurology recommendations for diagnosis, management, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired autoimmune disorder that leads to progressive motor and sensory impairment, resulting in significant morbidity. While the incidence rates vary, CIDP remains a challenging condition requiring a standardized and optimized approach to diagnosis and management. In Brazil, a middle-income country with substantial regional disparities in healthcare access, the availability of specialized neuromuscular centers is uneven, creating obstacles to timely and effective treatment. To address these challenges, the Brazilian Acade

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… associated nephropathy, tremor, sensory ataxia, and distal weakness 46 CASPR | Acute/subacute, neuropathic pain 46 NF-155 | Early onset, tremor, high CSF protein, early axonal loss, good response to rituximab 46 Multiple myeloma | Bone osteoblastic lesion, hypocalcemia, renal impairment 47 Motor > sensory | Porphyria … Doi: 172 10.1111/jns.12638 38873841 10.1111/jns.12638 48 Gerischer L M Scheibe F Nümann A Köhnlein M Stölzel U Meisel A Acute porphyrias - A neurological perspective Brain Behav 2021 11 11 e2389 10.1002/brb3.2389 34661997 PMC8613433 49 Cortese A Simone R Sullivan R Vandrovcova J Tariq H Yau W Y Biallelic …

Heme Metabolism-Related Gene TENT5C is a Prognostic Marker and Investigating Its Immunological Role in Colon Cancer.

BackgroundThere is a strong correlation between consuming high amounts of heme and an elevated risk of developing various types of cancer, including colorectal cancer. However, the role of heme metabolism-related genes (HRGs) in colorectal cancer remains unclear. Our study aimed to identify prognostic markers for colorectal cancer patients based on these genes.MethodsThe heme metabolism score was assessed using gene set variation analysis (GSVA). Potential prognostic HRGs were identified from the TCGA-COAD dataset using LASSO and COX regression analyses. The expression level of TENT5C was vali