Structure-Activity Relationship of Ciprofloxacin towards S-Spike Protein of SARS-CoV-2: Synthesis and Evaluation.

The recent outbreak of the coronavirus (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has posed serious threats to global health systems. Although several directions have been put by the WHO for effective treatment, use of antibiotics, particularly ciprofloxacin, in suspected and acquired Covid-19 patients has raised an even more serious concern of antibiotic resistance. Ciprofloxacin has been reported to inhibit entry of SARS-CoV-2 into the host cells via interacting with the spike (S) protein.

Challenges in the Management of Hemorrhagic Shock in Patients with Bombay Blood Group in the ICU: What the H?

Bhosale SJ, Joshi M, Dhakane P, Ojha S, Kulkarni AP. Challenges in the Management of Hemorrhagic Shock in Patients with Bombay Blood Group in the ICU: What the H? Indian J Crit Care Med 2024;28(12):1185-1186.

Pelvic regional control with 25Gy in 5 fractions in SBRT for high risk prostate cancer: Pooled prospective outcomes from the SHARP consortium.

Aim: To evaluate the efficacy of 25Gy/5# prophylactic pelvic nodal irradiation for regional control during stereotactic radiotherapy (SBRT) for high risk prostate cancer.

Methods: The multinational XXXX consortium database of patients treated with curative-intent prostate SBRT for high risk prostate cancer was queried for prophylactic radiotherapy 25Gy/5# to the pelvic lymph nodes. Details of Phoenix-defined biochemical failure, and location of recurrence (local, regional, or distant) were extracted.

RAPID-CRISPR: Highly Sensitive Diagnostic Assay for Detection of PML-RARA Isoforms in Acute Promyelocytic Leukemia.

Acute promyelocytic leukemia (APL), distinguished by the presence of PML-RARA fusion transcript, is a medical emergency due to its high early death rate, which is preventable when diagnosed early. Current diagnostic methods are precise and reliable but are time-intensive, require sophisticated instruments and analytical expertise. This study has Redefined APL IDentification by CRISPR system (RAPID-CRISPR) to rapidly (<3hrs) detect PML-RARA.

14-3-3ε conditional knockout mice exhibit defects in the development of the epidermis.

The epidermis is a stratified epithelium that functions as the first line of defense against pathogenic invasion and acts as a barrier preventing water loss. In this study, we aimed to decipher the role of 14-3-3ε in the development of the epidermis. We report that loss of 14-3-3ε in the epidermis of juvenile and adult mice reduces cell division in the basal layer and increases the percentage of cells with multiple centrosomes, leading to a reduction in the thickness of the basal and stratified layers.

Disabled 2 (Dab2) Regulates Tumour Progression in Skin Squamous Cell Carcinoma.

Dab2 is an endocytic adaptor protein involved in various physiological processes and signaling pathways. Dab2 is deregulated in various cancers; however, its role in skin squamous cell carcinoma ( SCC) has not been elucidated yet. In the present study, we used the DMBA/TPA induced murine skin carcinogenesis model to examine the role of Dab2 in skin tumour progression.

Prevalence of Oral Potentially Malignant Lesions, Tobacco use, and Effect of Cessation Strategies among Solid Waste Management workers in Northern India: a pre-post intervention study.

Background: India bears the highest global burden of oral cancer, despite having an operational tobacco cessation framework. Occupational groups like solid waste management personnel face significant health challenges due to prevalent tobacco use, leading to oral potentially malignant lesions and oral cancer. Enhanced tobacco control strategies are essential for these groups.

Comparative analysis of canine and human HtrA2 to delineate its role in apoptosis and cancer.

Therapeutically, targeting the pro- and anti-apoptotic proteins has been one of the major approaches behind devising strategies to combat associated diseases. Human high-temperature requirement serine protease A2 (hHtrA2), which induces apoptosis through both caspase-dependent and independent pathways is implicated in several diseases including cancer, ischemic heart diseases, and neurodegeneration, thus making it a promising target molecule. In the recent past, the canine model has gained prominence in the understanding of human pathophysiology that was otherwise limited to the rodent system.

14-3-3σ restricts YY1 to the cytoplasm, promoting therapy resistance, and tumor progression in colorectal cancer.

14-3-3σ functions as an oncogene in colorectal cancer and is associated with therapy resistance. However, the mechanisms underlying these observations are not clear. The results in this report demonstrate that loss of 14-3-3σ in colorectal cancer cells leads to a decrease in tumor formation and increased sensitivity to chemotherapy.

Targeting type I DED interactions at the DED filament serves as a sensitive switch for cell fate decisions.

Activation of procaspase-8 in the death effector domain (DED) filaments of the death-inducing signaling complex (DISC) is a key step in apoptosis. In this study, a rationally designed cell-penetrating peptide, DEDid, was engineered to mimic the h2b helical region of procaspase-8-DED2 containing a highly conservative FL motif. Furthermore, mutations were introduced into the DEDid binding site of the procaspase-8 type I interface.

Late Urinary Toxicity After Extreme or Moderate Hypofractionated Prostate Radiation Therapy in Patients With Prior Transurethral Resection of Prostate.

Purpose: To study the late urinary toxicity in patients with prostate cancer with prior transurethral resection of prostate (TURP) and treated with hypofractionated prostate radiation therapy.

Methods And Materials: Patients diagnosed with prostate cancer, with a prior TURP, and treated with moderate or extreme hypofractionated intensity-modulated radiation therapy (moderate hypofractionated radiation therapy [MHRT], stereotactic body radiation therapy [SBRT]), were included in this study. Severity and duration of urinary symptoms observed during serial follow-up after at least 3 months from radiation therapy were graded per National Cancer Institute Common Terminology Criteria for Adverse Events v5.

Identification of Rare EIF3E::RSPO2 Fusion in Recurrent and Aggressive Urachal Adenocarcinoma.

Introduction: Urachal cancer (UC) is a rare genitourinary malignancy arising from the urachus, an embryonic remnant of the placental allantois. Its diagnosis remains ambiguous with late-stage cancer detection and represents a highly aggressive disease. Due to its rarity, there is no clear consensus on molecular signatures and appropriate clinical management of UC.

Ribosomal dormancy at the nexus of ribosome homeostasis and protein synthesis.

Dormancy or hibernation is a non-proliferative state of cells with low metabolic activity and gene expression. Dormant cells sequester ribosomes in a translationally inactive state, called dormant/hibernating ribosomes. These dormant ribosomes are important for the preservation of ribosomes and translation shut-off.

Dab2 (Disabled-2), an adaptor protein, regulates self-renewal of hair follicle stem cells.

Disabled 2 (Dab2), an adaptor protein, is up regulated in the hair follicle stem cells (HFSCs); however, its role in any tissue stem cells has not been studied. In the present study, we have reported that Dab2 conditional knockout (Dab2-cKO) mice exhibited a delay in the HF cycle due to perturbed activation of HFSCs. Further, Dab2-cKO mice showed a reduction in the number of HFSCs and reduced colony forming ability of HFSCs.

Patterns of Failure After Prostate-Only Radiotherapy in High-Risk Prostate Cancer: Implications for Refining Pelvic Nodal Contouring Guidelines.

Purpose: To study prostate specific membrane antigen - positron emission tomography (GaPSMA-PETCT) based patterns of relapse at biochemical failure (BCF) after prostate-only radiotherapy (PORT) in high-risk (HR) prostate cancer and its implications on pelvic contouring recommendations.

Methods And Materials: Patients with clinico-radiological high-risk node-negative prostate cancer treated with curative PORT and androgen deprivation therapy (ADT), either within the POP-RT randomised trial or off trial, who underwent a GaPSMA-PETCT upon BCF were included. Patterns of regional and distant recurrence on GaPSMA-PETCT were studied.

Late Urinary Toxicity and Quality of Life With Pelvic Radiation Therapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase 3 Trial.

Purpose: The POP-RT phase 3 randomized trial showed improved biochemical failure-free survival and metastasis-free survival with whole pelvic radiation therapy versus prostate-only radiation therapy for high and very high-risk prostate cancer, albeit with worse RTOG late urinary toxicity. We report updated late urinary adverse effects and bladder dose-effect relations within this trial.

Methods And Materials: Late urinary toxicity and the cumulative severity of each symptom during the follow-up period were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.

cFLIP - An interacting partner and a novel substrate for pro-apoptotic serine protease HtrA2.

Background: HtrA2, a pro-apoptotic protease, plays a crucial role in apoptosis by cleaving inhibitory and anti-apoptotic proteins by translocating from mitochondria to the cytosol. Prior studies in ischemic cells have indicated that cytosolic HtrA2 triggers cFLIP degradation, plausibly through direct interaction. In this study, we have characterized the cFLIP protein, validated its interaction with HtrA2, and demonstrated that cFLIP is also a substrate of HtrA2.

Brachytherapy Workflow Practices: Analysis of Different Workflow Scenarios in Patients With Cervical Cancer and Impact on IGBT Implementation-An IAEA Study.

Purpose: The workflow of brachytherapy (BT) is an essential aspect of treatment to consider in image-guided brachytherapy (IGBT). It has an overarching effect influencing patient throughput and the number of cancer treatments that can be performed as it occupies equipment, space, and personnel. There is limited research addressing this issue.

Radiotherapy in metastatic bladder cancer.

Purpose: To review available and emerging evidence of radiotherapy for symptom management and disease control in metastatic bladder cancer.

Methods: A literature search and subsequent cross-referencing were carried out for articles in the PubMed and Scopus databases using terms 'radiotherapy' OR 'palliative radiation therapy' with 'metastatic bladder cancer' OR 'advanced bladder cancer' between 1990 and 2023, excluding articles with no English translation.

Results: Palliative radiotherapy is an effective and accessible treatment for the alleviation of haematuria and pain due to the primary and metastatic disease.

Recent advancements in targeted protein knockdown technologies-emerging paradigms for targeted therapy.

A generalized therapeutic strategy for various disease conditions, including cancer, is to deplete or inactivate harmful protein targets. Various forms of protein or gene silencing molecules, e.g.

Stereotactic body radiation therapy for prostate cancer after surgical treatment of prostatic obstruction: Impact on urinary morbidity and mitigation strategies.

In the past decade, stereotactic body radiation therapy (SBRT) has emerged as a valid treatment option for patients with localized prostate cancer. Despite the promising results of ultra-hypofractionation in terms of tolerance and disease control, the toxicity profile of SBRT for prostate cancer patients with a history of surgical treatment of benign prostate hyperplasia is still underreported. Here we present an overview of the available data on urinary morbidity for prostate cancer patients treated with SBRT after prior surgical treatments for benign prostate hyperplasia.

Transitioning India to advanced image based adaptive brachytherapy: a national impact analysis of upgrading National Cancer Grid cervix cancer guidelines.

Background: High-dose-rate image guided brachytherapy (IGBT) for cervical cancer leads to improved local control and reduced toxicity and is a critical component of treatment. However, transition to IGBT requires capacity upscaling. An institutional activity mapping and national impact analysis of such a transition were undertaken to understand feasibility.