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Understanding Rare Anemias: Emerging Frontiers for Diagnosis and Treatment.

Background-This review provides a comprehensive overview of rare anemias, emphasizing their hereditary and acquired causes, diagnostic advancements, and evolving treatment strategies. It outlines the significance of rare anemias within public health, historical challenges in recognition and treatment, and the role of European initiatives like ENERCA and EuroBloodNet in advancing care. Content-This document discusses diagnostic technologies like next-generation sequencing and the impact of artificial intelligence, alongside the promising avenues of gene therapy, targeted drug treatments, and st

Erythropoiesis: insights into pathophysiology and treatments in 2017.

Erythropoiesis is a tightly-regulated and complex process originating in the bone marrow from a multipotent stem cell and terminating in a mature, enucleated erythrocyte.Altered red cell production can result from the direct impairment of medullary erythropoiesis, as seen in the thalassemia syndromes, inherited bone marrow failure as well as in the anemia of chronic disease. Alternatively, in disorders such as sickle cell disease (SCD) as well as enzymopathies and membrane defects, medullary erythropoiesis is not, or only minimally, directly impaired. Despite these differences in pathophysiolo

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant atten

Integumentary System

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The Emerging Role of Oncolytic Virotherapy in Glioblastoma Management.

Glioblastoma (GBM) is an aggressive and common form of central nervous system primary malignant tumor in adults. GBM accounts for about half of all gliomas. Despite maximal resection, radiotherapy, and temozolomide, median survival is still 12-15 months because of tumor heterogeneity, diffuse infiltration, and therapeutic resistance. Recurrence is nearly universal, underscoring the need for novel therapies. Oncolytic virotherapy demonstrates a promising strategy that combines direct tumor cell lysis with immune activation. Tumor-selective viruses replicate within malignant cells, induce cell d

Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.

Endoplasmic reticulum (ER) stress is a key cellular mechanism that is important in the development of many diseases, including cancer. Since the discovery of the unfolded protein response (UPR), research has greatly improved our understanding of how ER stress affects cellular functions, especially protein folding and adaptation to stress. The UPR consists of three main branches: IRE1, ATF6, and PERK, each of which is crucial for regulating stress responses, protein homeostasis, and apoptosis. These pathways normally help cells handle stress effectively; however, excessive or prolonged activati

Unveiling the Complexities of Hereditary Angioedema.

Hereditary angioedema (HAE) is a rare and potentially life-threatening genetic disorder, constituting approximately 2% of all clinical cases of angioedema, with a global prevalence estimated between 1 in 50,000 and 1 in 150,000 individuals. The condition affects individuals of all genders and ethnic backgrounds without significant variation. HAE is classified into three types. Type I HAE, which accounts for 85% of cases, is characterized by a deficiency of the C1 esterase inhibitor (C1-INH) gene. Type II HAE, making up 15% of cases, involves a dysfunctional C1-INH. Type III HAE, which represen

Endothelial TFEB signaling-mediated autophagic disturbance initiates microglial activation and cognitive dysfunction.

Cognitive impairment caused by systemic chemotherapy is a critical question that perplexes the effective implementation of clinical treatment, but related molecular events are poorly understood. Herein, we show that bortezomib exposure leads to microglia activation and cognitive impairment, this occurs along with decreased nuclear translocation of TFEB (transcription factor EB), which is linked to macroautophagy/autophagy disorder, STAT3 (signal transducer and activator of transcription 3) phosphorylation and IL23A (interleukin 23 subunit alpha) expression. Pharmacological enhancement of TFEB

Targeting the two-pore channel 2 in cancer progression and metastasis.

The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions

Pharmacological Treatments and Therapeutic Drug Monitoring in Patients with Chronic Pain.

Pain is an unpleasant sensory and emotional experience that affects every aspect of a patient's life and which may be treated through different pharmacological and non-pharmacological approaches. Analgesics are the drugs most commonly used to treat pain, and in specific situations, the use of opioids may be considered with caution. These drugs, in fact, do not always induce optimal analgesia in patients, and several problems are associated with their use. The purpose of this narrative review is to describe the pharmacological approaches currently used for the management of chronic pain. We rev

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… Lastly, activation of ORs in the reticular formation increases the duration of light sleep and decreases that of deep and REM sleep [ 29 ]. …

Sclerosing diseases of the skin.

Sclerosing skin diseases comprise a group of distinct dermatological conditions characterized by fibrotic changes that may severely impair patients' quality of life. These conditions often present with cutaneous manifestations and, in some cases, may extend to extracutaneous tissues, potentially resulting in significant morbidity and mortality. This review explores the current understanding of the four most prevalent sclerosing skin diseases - localized scleroderma (morphea), systemic sclerosis (SSc), scleromyxedema, and scleredema adultorum of Buschke - as well as sclerotic conditions induced

Fracture Risk Evaluation of Bone Metastases: A Burning Issue.

Major progress has been achieved to treat cancer patients and survival has improved considerably, even for stage-IV bone metastatic patients. Locomotive health has become a crucial issue for patient autonomy and quality of life. The centerpiece of the reflection lies in the fracture risk evaluation of bone metastasis to guide physician decision regarding physical activity, antiresorptive agent prescription, and local intervention by radiotherapy, surgery, and interventional radiology. A key mandatory step, since bone metastases may be asymptomatic and disseminated throughout the skeleton, is t

Management and Clinical Outcomes of Scleredema Diabeticorum: A Scoping Review.

Background/objectivesThe objective of this scoping review was to systematically map the available evidence for the management of scleredema diabeticorum (SD) to summarize the documented clinical outcomes with the aim to inform clinical practice and identify research gaps.MethodsWe conducted a scoping review identifying studies published in English from January 2005 to July 2025 through a comprehensive search of Scopus, MEDLINE, and the Cochrane Library. Eligible studies included randomized controlled trials, observational studies, case series, and case reports on treatment interventions and cl

Overview of Ayurveda and Ashwagandha: Bioactive Phytochemicals and Potential Applications to Gliomas.

Ayurveda is the traditional medical system of India and has been in use for more than 5000 years. The focus of Ayurveda is to maintain harmony and balance of the three Doshas (Vata, Pitta, Kapha), or life forces, that govern the physiology and health of each individual. Ashwagandha is considered one of the most useful plants in the Ayurvedic system for various illnesses, including cancer. Ethnopharmacological and phytochemical analyses have been elucidating the bioactive compounds in ashwagandha that mediate the anti-cancer effects. The most bioactive compounds appear to be the withanolides, i

Recombinant Oncolytic Viruses: Hexagonal Warriors in the Field of Solid Tumor Immunotherapy.

In the past decade, research on recombinant oncolytic viral agents in the treatment of solid tumors has evolved from the initial stage of simple genetic engineering to the current stage of multiple pipelines of parallel clinical application and combination therapy. Compared with T-VEC, the classical therapeutic agent that only expresses GM-CSF, which was approved in 2015, most new oncolytic virus designs include diverse gene constructs to reduce toxic effects, enhance multiple antitumor immunity, avoid immune clearance, or enhance tumor targeting. The single route of administration that activa

Diseases of the Nervous System

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… Clinicopathologic tests Sudden onset Normal temperature, pulse/heart rate slow to normal, nosebleed, skin laceration, bruising middle of forehead or poll Cerebral-brainstem reticular formation (ascending reticular activating system) Cerebral-brainstem reticular formation (ascending reticular activating … Clinicopathologic tests Sudden onset Normal temperature, pulse/heart rate slow to normal, nosebleed, skin laceration, bruising middle of forehead or poll | Cerebral-brainstem reticular formation (ascending reticular activating system) Cerebral-brainstem reticular formation (ascending reticular activating …

Coming of Age for Autotaxin and Lysophosphatidate Signaling: Clinical Applications for Preventing, Detecting and Targeting Tumor-Promoting Inflammation.

A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironmen

[Expert consensus on optimizing the multidisciplinary clinical pathways and management models for pulmonary function testing].

The promotion and application of pulmonary function tests (PFTs) in China have achieved preliminary success;however, numerous deficiencies persist in multidisciplinary PFT clinical application pathways and management. Current challenges remain in identifing target population, implementing pathways within and outside medical institutions, allocating hardware, training personnel, managing information, and assessing performance.The consensus aims to optimize multidisciplinary clinical pathways and management models for PFTs by leveraging information technology and strengthening organizational coo

Резюме

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Bone Metastasis of Breast Cancer: Molecular Mechanisms and Therapeutic Strategies.

Bone metastasis is a common complication of many types of advanced cancer, including breast cancer. Bone metastasis may cause severe pain, fractures, and hypercalcemia, rendering clinical management challenging and substantially reducing the quality of life and overall survival (OS) time of breast cancer patients. Studies have revealed that bone metastasis is related to interactions between tumor cells and the bone microenvironment, and involves complex molecular biological mechanisms, including colonization, osteolytic destruction, and an immunosuppressive bone microenvironment. Agents inhibi