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Химокины как терапевтические мишени для множественного склероза: пространственная и хронологическая перспектива.

Множественный склероз (MS) — хроническое автовоспалительное заболевание неизвестного происхождения, характеризующееся инфильтрацией иммунных клеток в цельную ткань, центральную нервную систему (ЦНС), приводящее к локальному и/или системному воспалению. Симптомы варьируются в зависимости от походного расстройства, нарушения зрения, а также расстройства знаний и памяти и решаются с помощью кортикостероидов и/или иммунодепрессивных агентов. Однако некоторые пациенты не реагируют на это лечение, что также может повысить риск серьезных инфекций. Поэтому по-прежнему существует необходимость в опреде

Роль оси CXCL12/CXCR4/CXCR7 в когнитивном повреждении, связанном с нейродегенеративными заболеваниями.

Нейродегенеративные заболевания, включая болезнь Альцгеймера (AD), болезнь Паркинсона (PD), множественный склероз (MS) и амиотропический боковой склероз (ALS), характеризуются постепенной нейронной потерей и когнитивным расстройством (CI). Ось Cystine-X-cystine chemokine ligand 12 (CXCL12)/CXC chemokine рецептор типа 4 (CXCR4)/CXC chemokine рецептор типа 7 (CXCR7) стала критическим молекулярным путем развития CI в этих расстройствах. В настоящем обзоре изучается роль этой оси в патогенезе интеллигенции в связи с этими нейродегенеративными заболеваниями, синтезируются имеющиеся данные и ее посл

Clinical review: specific aspects of acute renal failure in cancer patients.

Acute renal failure (ARF) in cancer patients is a dreadful complication that causes substantial morbidity and mortality. Moreover, ARF may preclude optimal cancer treatment by requiring a decrease in chemotherapy dosage or by contraindicating potentially curative treatment. The pathways leading to ARF in cancer patients are common to the development of ARF in other conditions. However, ARF may also develop due to etiologies arising from cancer treatment, such as nephrotoxic chemotherapy agents or the disease itself, including post-renal obstruction, compression or infiltration, and metabolic o

Естественные и синтетические АМП из Латинской Америки по всему спектру технологий и приложений в области разнообразия.

Биоразнообразие в Латинской Америке примерно 60% в целом по миру, подпитывая научные исследования в области природных продуктов, весьма значимой области открытия наркотиков по сей день. Это сопровождается увеличением числа антимикробных пептидов (АМП), полученных из натуральных продуктов в регионе, которые за последнее десятилетие были переработаны путем модификации, усовершенствования и уточнения их физико-химических свойств и антимикробной эффективности с использованием подходов, которые варьируются от изучения рациональной конструкции и соотношения структуры-активности (САР) до методов иску

Revisiting strategies to target ABC transporter-mediated drug resistance in CNS cancer.

A significant number of anticancer drugs fail to treat primary and metastatic brain tumors primarily because of the complex blood-brain barrier (BBB) and overexpression of ATP-binding cassette (ABC) transporters, which decrease drug penetration into the central nervous system and ultimately into tumors. It is noteworthy that the ABC transporters, ABCB1 [known as P-glycoprotein (P-gp)] and ABCG2 [known as breast cancer resistance protein (BCRP)], are overexpressed in brain tumors, including common gliomas. The co-presence of these transporters may negate the inhibition of either transporter, pa

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… Thus, the substrate in the intracellular space will first bind to the hydrophobic cavity, whereas the ABCG2 transporter is in the inward-facing conformation 64 . This process induces conformational changes in the NBD, resulting in productive ATP binding and hydrolysis. …

Emergency Care

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Regulatory T cells and immune escape in HCC: understanding the tumor microenvironment and advancing CAR-T cell therapy.

Liver cancer, which most commonly manifests as hepatocellular carcinoma (HCC), is the sixth most common cancer in the world. In HCC, the immune system plays a crucial role in the growth and proliferation of tumor cells. HCC achieve immune escape through the tumor microenvironment, which significantly promotes the development of this cancer. Here, this article introduces and summarizes the functions and effects of regulatory T cells (Tregs) in the tumor microenvironment, highlighting how Tregs inhibit and regulate the functions of immune and tumor cells, cytokines, ligands and receptors, etc, t

Antibody-Drug Conjugates in Contemporary Oncology: A Clinical Perspective on Dose Optimization, Sequencing, and Combination Strategies.

Antibody-drug conjugates (ADCs) have matured from a technically challenging concept into an established therapeutic platform across hematologic and solid malignancies. By linking a monoclonal antibody to a potent cytotoxic payload, ADCs seek to increase tumor-directed drug delivery while limiting systemic exposure; however, clinical performance depends on much more than target expression. Target accessibility, antigen density and heterogeneity, internalization, intracellular trafficking, linker stability, payload properties, drug-to-antibody ratio, bystander effect, tumor penetration, and host

An understanding of mitochondria and its role in targeting nanocarriers for diagnosis and treatment of cancer.

Nanotechnology has changed the entire paradigm of drug targeting and has shown tremendous potential in the area of cancer therapy due to its specificity. In cancer, several targets have been explored which could be utilized for the better treatment of disease. Mitochondria, the so-called powerhouse of cell, portrays significant role in the survival and death of cells, and has emerged as potential target for cancer therapy. Direct targeting and nanotechnology based approaches can be tailor-made to target mitochondria and thus improve the survival rate of patients suffering from cancer. With thi

Integrated Network Pharmacology Approach for Drug Combination Discovery: A Multi-Cancer Case Study.

Despite remarkable efforts of computational and predictive pharmacology to improve therapeutic strategies for complex diseases, only in a few cases have the predictions been eventually employed in the clinics. One of the reasons behind this drawback is that current predictive approaches are based only on the integration of molecular perturbation of a certain disease with drug sensitivity signatures, neglecting intrinsic properties of the drugs. Here we integrate mechanistic and chemocentric approaches to drug repositioning by developing an innovative network pharmacology strategy. We developed

Acquired platelet disorders.

Platelets are essential to primary hemostasis, and defects in their number or function can lead to clinically significant bleeding or thrombosis. Acquired platelet disorders are far more common than the inherited forms and arise in a wide range of settings, including drug exposure, autoimmune, systemic, and critical illnesses. This review examines current understanding of the mechanisms driving acquired platelet dysfunction and outlines the diagnostic and therapeutic approaches that are shaping contemporary standards of care. Drug-related and immune-mediated platelet defects remain the most re

Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance.

One of the greatest obstacles to current cancer treatment efforts is the development of drug resistance by tumors. Despite recent advances in diagnostic practices and surgical interventions, many neoplasms demonstrate poor response to adjuvant or neoadjuvant radiation and chemotherapy. As a result, the prognosis for many patients afflicted with these aggressive cancers remains bleak. The insulin-like growth factor (IGF) signaling axis has been shown to play critical role in the development and progression of various tumors. Many basic science and translational studies have shown that IGF pathw

От ожирения до митохондриальной дисфункции в периферальных тканях и в центральной нервной системе.

Ожирение - это состояние хронического низкосортного воспаления, затрагивающего периферийные органы тела, а также центральную нервную систему. Дефункция жировой ткани, возникающая в условиях ожирения, является ключевым фактором возникновения и развития различных заболеваний, включая нейродегенеративные расстройства. Митохондрия, ключевые органеллы в производстве клеточной энергии, играет важную роль в этой дисфункции тканей. В многочисленных исследованиях подчеркивается тесная связь между ожирением и дисфункцией митохондриалов адипоцита, что приводит к чрезмерному производству ROS и воспалению

Development, efficacy and side effects of antibody‑drug conjugates for cancer therapy (Review).

Antibody-drug conjugates (ADCs) are anticancer drugs that combine cytotoxic small-molecule drugs (payloads) with monoclonal antibodies through a chemical linker and that transfer toxic payloads to tumor cells expressing target antigens. All ADCs are based on human IgG. In 2009, the Food and Drug Administration (FDA) approved gemtuzumab ozogamicin as the initial first-generation ADC. Since then, at least 100 ADC-related projects have been initiated, and 14 ADCs are currently being tested in clinical trials. The limited success of gemtuzumab ozogamicin has led to the development of optimization

The interplay of mitochondrial dysfunction and altered metabolic pathways in glioblastoma.

Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor, characterized by rapid progression, treatment resistance, and poor prognosis, with a survival rate of less than five years despite advances in medical interventions. A hallmark of GBM is metabolic reprogramming, which supports tumor growth and progression. Mitochondrial dysfunction plays a critical role in this metabolic shift by altering energy production and disrupting key cellular pathways. However, the precise molecular mecha-nisms underlying these alterations remain inadequately understood. This review highlights th

A Novel Paradigm for Targeting Challenging Targets: Advancing Technologies and Future Directions of Molecular Glue Degraders.

Molecular glue degraders (MGDs) constitute a class of innovative therapeutic agents within the field of targeted protein degradation (TPD). In contrast to proteolysis-targeting chimeras (PROTACs), MGDs induce protein degradation by stabilizing the interaction between an E3 ubiquitin ligase and a target protein. They typically exhibit favorable drug-like characteristics, including lower molecular weight and enhanced bioavailability. Although their discovery was historically serendipitous, recent advances in high-throughput screening, bioinformatics, and artificial intelligence are enabling more

Ataxia-Telangiectasia and Associated Bronchiectasis: Case Report and Literature Review.

Ataxia-telangiectasia is a rare, autosomal recessive primary immunodeficiency caused by mutations in the ATM gene on chromosome 11, which encodes a serine-threonine kinase essential for the recognition and repair of DNA double-strand breaks. The disease is characterized by progressive neurological impairment, immunological dysfunction, and an increased susceptibility to recurrent infections and malignancies. Pulmonary involvement represents a major source of morbidity and frequently arises from chronic infections, aspiration, and impaired airway clearance, ultimately leading to the development

Colorectal cancer with first known case of simultaneous bilateral tibial metastases.

The most common osseous metastatic regions for colorectal cancer are the lumbar and sacral vertebrae and the pelvis. There are few reported cases of isolated solitary tibial metastasis, and simultaneous bilateral solitary tibial metastases in colorectal cancer are even rarer. A 62-year-old female patient was admitted to our inpatient clinic 3 years after receiving initial chemotherapy for a rectosigmoid adenocarcinoma with liver metastasis. The patient complained of left leg pain. Radiographs and magnetic resonance imaging revealed a 3- × 3-cm mass in the right proximal tibia and a 2- × 7-cm m

A review of feline infectious peritonitis virus infection.

Feline infectious peritonitis (FIP) is an infectious disease characterized by non-specific laboratory changes and clinical signs. Clinical symptoms include anorexia, jaundice, fever, and weight loss. Moreover, some lesions are found in the digestive and respiratory systems. FIP, whose virulence varies, cannot be distinguished using several diagnostic methods. Moreover, feline coronaviruses (FCoVs) can be classified into two serotypes based on differences in their amino acid sequences, spike (S) protein sequences, and antibody (Ab) neutralization. There are two pathotypes, namely those caused b

Появляющаяся роль BTK Inhibitors в многоразовом склерозе: от иммунобиологии к клиническому переводу.

Множественный склероз (MS), аутоиммунное заболевание, предполагает периферическую иммунную активацию, за которой следует воспаление CNS в разрозненной форме. Несмотря на то, что высокоэффективные методы коррекции заболеваний (HO-DMT) оказались эффективными в борьбе с рецидивами у пациентов с синдромом MS, они не позволяют эффективно ориентироваться на хроническую микрогильевую активацию и удушающие повреждения у пациентов с синдромом MS. Тейросиновые ингибиторы киназы Брютона (BTKis), которые являются перорально активными и способными пересечь мозговой барьер, были признаны эффективными для мо