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Clinical course and biomarkers in patients with type 1 Gaucher disease and Parkinson's disease: A retrospective cohort study.

INTRODUCTION: Pathogenic variants in GBA1, the gene encoding beta-glucocerebrosidase, are significant genetic risk factors for Parkinson's disease (PD). Patients with type 1 Gaucher disease (GD1), caused by biallelic GBA1 variants, have approximately six-fold higher lifetime risk for PD compared to the general population. However, few studies have described the clinical presentation of GD-associated PD (GD-PD) in GD1 patients. We describe the variable presentation of PD and evaluate clinical characteristics and biomarkers in a cohort of patients with concurrent diagnoses of GD-PD. METHODS: Re

Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a hematologic malignancy associated with high morbidity and mortality. Here we describe a case of a patient with AML who presented a partial response after utilization of the non-steroidal anti-inflammatory drug nimesulide. The response was characterized by complete clearance of peripheral blood blasts and an 82% decrease of bone marrow blasts associated with myeloblast differentiation. We have then shown that nimesulide induces in vitro cell death and cell cycle arrest in all AML cell lines (HL-60, THP-1, OCI-AML2, and OCI-AML3). Weighted Correlation Network An

The pro-apoptotic paradox: the BH3-only protein Bcl-2 interacting killer (Bik) is prognostic for unfavorable outcomes in breast cancer.

Breast cancer is the leading cause of cancer-associated deaths in women worldwide. Clinical biomarkers give information on disease progression and identify relevant biological pathways. A confounding factor that uncouples markers from disease outcome is the ability of tumor cells to mutate and evade clinical intervention. Therefore, we focussed on apoptotic genes that modulate tumor regression. Using gene and tissue microarray analyses, we identified an association of Bcl-2 interacting killer (Bik) with poor breast cancer prognosis. Bik prognostic ability was independent of Estrogen Receptor/P

Renaissance of Traditional Mineral Drugs in Cancer: Advanced Delivery Strategies and Bioengineering Approaches.

Traditional mineral drugs represent an underexploited reservoir of natural antitumor agents; however, their clinical translation has historically been hindered by poor bioavailability, non-specific biodistribution, and dose-limiting toxicity. This review comprehensively examines the pharmacological mechanisms and modern formulation strategies driving the renaissance of mineral-based oncology therapeutics. We highlight how mineral drugs exert potent anticancer effects through interconnected pathways, including regulated cell death (e.g., apoptosis, ferroptosis), cell-cycle arrest, and immunomod

Перекресток между диабетом и болезнью Альцгеймера: Молекулярная перспектива.

Общемировая распространенность видов 2 Заболевание сахарным диабетом (T2DM) и болезнью Альцгеймера (AD) значительно возрастает в зависимости от возраста. Растущие данные подтверждают концептуализацию АД как типа 3 диабет, термин, предлагаемый для описания метаболического заболевания, вызванного главным образом поврежденной инсулиновой сигнализацией и инсулиновой резистентностью в мозге. В рамках этого обзора изучаются общие молекулярные механизмы, лежащие в основе как T2DM, так и AD, включая хроническую нейроинфламму, окислительный стресс, митохондриальную дисфункцию и поврежденный метаболизм

Сравнительный анализ нервно-воспалительных путей болезни Альцгеймера, болезни Паркинсона и множественного склероза: понимание сходства и различий.

Растет интерес к нейродегенеративным болезням, усугубляющим значительное социально-экономическое бремя, вызванное старением общества. Несмотря на то, что каждая болезнь имеет различные этиологии, нейроинфламмация, как считается, играет решающую роль в болезни Альцгеймера (AD), болезни Паркинсона (PD) и множественном склерозе (MS). Помимо патогенной функции воспаления мозга, растет число свидетельств того, что иммунная реакция необходима для нейрорегенерации. Этот обзор сравнивает и контрастирует с нейроинфламационными путями, которые характерны для различных нейродегенеративных заболеваний. В

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… In mouse microglia, TLR2 knockout decreases α-synuclein uptake ( Kim et al., 2013 ). α-synuclein is incorporated into autophagosomes through the activation of the TLR-4–NFκB pathway ( Choi et al., 2020b ; Choi et al., 2020a ). …

A clinicopathologic study of malignancy in VCP-associated multisystem proteinopathy.

BACKGROUND: Valosin containing protein (VCP) is an important protein with many vital functions mostly related to the ubiquitin-proteasome system that provides protein quality control. VCP-associated inclusion body myopathy with Paget disease of bone and frontotemporal dementia, also termed VCP disease and multisystem proteinopathy (MSP 1), is an autosomal dominant disorder caused by monoallelic variants in the VCP gene on human chromosome 9. VCP has also been strongly involved in cancer, with over-activity of VCP found in several cancers such as prostate, pancreatic, endometrial, esophageal ca

Advances in Understanding Mitochondrial MicroRNAs (mitomiRs) on the Pathogenesis of Triple-Negative Breast Cancer (TNBC).

Triple-negative breast cancer (TNBC) is characterized by poor outcome and the most challenging breast cancer type to treat worldwide. TNBC manifests distinct profile of mitochondrial functions, which dictates reprogrammed metabolism, fosters tumor progression, and notably serves as therapeutic targets. Mitochondrial microRNAs (mitomiRs) are a group of microRNAs that critically modulate mitochondrial homeostasis. By a pathway-centric manner, mitomiRs tightly orchestrate metabolic reprogramming, redox status, cell apoptosis, mitochondrial dynamics, mitophagy, mitochondrial DNA (mtDNA) maintenanc

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… Mitochondrial fission acts to promote segregation of damaged mitochondria, which subsequently facilitates mitochondrial fragments of the appropriate size for engulfment by autophagosomes. …

Fate of Antibody-Drug Conjugates in Cancer Cells.

Antibody-Drug Conjugates (ADCs) are a class of cancer therapeutics that combines antigen specificity and potent cytotoxicity in a single molecule as they are comprised of an engineered antibody linked chemically to a cytotoxic drug. Four ADCs have received approval by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) and can be prescribed for metastatic conditions while around 60 ADCs are currently enrolled in clinical trials. The efficacy of an ADC greatly relies on its intracellular trafficking and processing of its components to trigger tumor cell death. A limite

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… It reaches autophagosomes and later autolysosomes where it is degraded leading to the release of DM1. …

Cancer-Therapy-Related Cardiac Dysfunction: Latest Advances in Prevention and Treatment.

The increasing efficacy of cancer therapies has significantly improved survival rates, but it has also highlighted the prevalence of cancer-therapy-related cardiac dysfunction (CTRCD). This review provides a comprehensive overview of the identification, monitoring, and management of CTRCD, a condition resulting from several treatments, such as anthracyclines, HER2-targeted therapies, target therapies, and radiotherapy. The paper includes a discussion of the mechanisms of CTRCD associated with various cancer treatments. Early detection through serum biomarkers and advanced imaging techniques is

Drug Repurposing for Cancer Treatment: A Comprehensive Review.

Cancer ranks among the primary contributors to global mortality. In 2022, the global incidence of new cancer cases reached about 20 million, while the number of cancer-related fatalities reached 9.7 million. In Saudi Arabia, there were 13,399 deaths caused by cancer and 28,113 newly diagnosed cases of cancer. Drug repurposing is a drug discovery strategy that has gained special attention and implementation to enhance the process of drug development due to its time- and money-saving effect. It involves repositioning existing medications to new clinical applications. Cancer treatment is a therap

Fasting-Mimicking Diet Inhibits Autophagy and Synergizes with Chemotherapy to Promote T-Cell-Dependent Leukemia-Free Survival.

Fasting mimicking diets (FMDs) are effective in the treatment of many solid tumors in mouse models, but their effect on hematologic malignancies is poorly understood, particularly in combination with standard therapies. Here we show that cycles of a 3-day FMD given to high-fat-diet-fed mice once a week increased the efficacy of vincristine to improve survival from BCR-ABL B acute lymphoblastic leukemia (ALL). In mice fed a standard diet, FMD cycles in combination with vincristine promoted cancer-free survival. RNA seq and protein assays revealed a vincristine-dependent decrease in the expressi

Диабет мелитус в множестве миэломы и связанных с ним расстройства плазменных клеток: обзор риска, прогноза и результатов.

Существует четкая связь между типом 2 сахарный диабет и общий риск заболевания раком. Однако исследования, посвященные оценке типа 2 Риск ДМ и множественной миэломы (ММ) ограничен, и связь менее ясна. Понимание воздействия давнишнего типа 2 Важнейшее значение имеет DM о системах органов и симптоматологии у пациентов с последующим диагнозом MM, а также потенциальные перекликающиеся токсичные вещества, связанные с лечением MM. В настоящем обзоре резюмируется роль вида 2 ДМ о рисках и результатах ММ и изучает различные механизмы, лежащие в основе этих ассоциаций. Более глубокое понимание этой асс

The novel role of circular RNA ST3GAL6 on blocking gastric cancer malignant behaviours through autophagy regulated by the FOXP2/MET/mTOR axis.

Gastric cancer (GC) ranks third in mortality among all cancers worldwide. Circular RNAs (circRNAs) play an important role in the occurrence and development of gastric cancer. Forkhead box P2 (FOXP2), as a transcription factor, is closely associated with the development of many types of tumours. However, the regulatory network between FOXP2 and circRNAs remains to be explored. In our study, circST3GAL6 was significantly downregulated in GC and was associated with poor prognosis in GC patients. Overexpression of circST3GAL6 inhibited the malignant behaviours of GC cells, which was mediated by in

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… Red spots represent autolysosomes while yellow spots represent autophagosomes. Three random fields were selected for puncta quantification. …

Metformin and Its Benefits for Various Diseases.

Metformin is a widely used biguanide drug due to its safety and low cost. It has been used for over 60 years to treat type 2 diabetes at the early stages because of its outstanding ability to decrease plasma glucose levels. Over time, different uses of metformin were discovered, and the benefits of metformin for various diseases and even aging were verified. These diseases include cancers (e.g., breast cancer, endometrial cancer, bone cancer, colorectal cancer, and melanoma), obesity, liver diseases, cardiovascular disease, and renal diseases. Metformin exerts different effects through differe

Towards Molecular Profiling in Multiple Myeloma: A Literature Review and Early Indications of Its Efficacy for Informing Treatment Strategies.

Multiple myeloma (MM), the second most common hematologic malignancy, is characterized by the clonal expansion of plasma cells. Despite dramatic improvements in patients' survival over the past decade due to advances in therapy exploiting novel molecular targets (immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies), the treatment of relapsed and refractory disease remains challenging. Recent studies confirmed complex, dynamic, and heterogeneous genomic alterations without unifying gene mutations in MM patients. In the current review, we survey recent therapeutic strategies,

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… Molecular chaperone GRP78 enhances aggresome delivery to autophagosomes to promote drug resistance in multiple myeloma. Oncotarget. 2015;6:3098–3110. doi: 10.18632/oncotarget.3075. 98. Wallington-Beddoe C.T., Sobieraj-Teague M., Kuss B.J., Pitson S.M. …

Role of Osteocytes in Myeloma Bone Disease: Anti-sclerostin Antibody as New Therapeutic Strategy.

Osteocytes are terminally differentiated cells of the osteoblast lineage. They are involved in the regulation of bone remodeling by increasing osteoclast formation or decreasing bone formation by the secretion of the osteoblast inhibitor sclerostin. Monoclonal antibody anti-sclerostin, Romosozumab, has been developed and tested in clinical trials in patients with osteoporosis. In the last years, the role of osteocytes in the development of osteolytic bone lesions that occurs in multiple myeloma, have been underlined. Myeloma cells increase osteocyte death through the up-regulation of both apop

Potential Therapeutic Targets of Resveratrol, a Plant Polyphenol, and Its Role in the Therapy of Various Types of Cancer.

Cancer is among the most prominent causes of mortality worldwide. Different cancer therapy modes employed, including chemotherapy and radiotherapy, have been reported to be significant in cancer management, but the side effects associated with these treatment strategies are still a health problem. Therefore, alternative anticancer drugs based on medicinal plants or their active compounds have been generating attention because of their less serious side effects. Medicinal plants are an excellent source of phytochemicals that have been recognized to have health-prompting effects through modulati

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… The LC3+ puncta formation, which characterized autophagosome formation, was also evidently dose dependently enhanced through resveratrol treatment, suggesting that resveratrol induced autophagy in liver cancer cells. … The data revealed that resveratrol enhances the presence of LC3-II and autophagosomes while also causing GFP-LC3 accumulation. Long-term exposure to this stilbenoid resulted in caspase-3 activation, cytosolic cytochrome c translocation, and apoptotic cell death [ 118 ]. …

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers.

Cancer is a serious disease with an increasing number of reported cases and high mortality worldwide. Gastrointestinal cancer defines a group of cancers in the digestive system, e.g., liver cancer, colorectal cancer, and gastric cancer. Coptidis Rhizoma (C. Rhizoma; Huanglian, in Chinese) is a classical Chinese medicinal botanical drug for the treatment of gastrointestinal disorders and has been shown to have a wide variety of pharmacological activity, including antifungal, antivirus, anticancer, antidiabetic, hypoglycemic, and cardioprotective effects. Recent studies on C. Rhizoma present sig

LAMP5 modulates IRF4 stability and nuclear transport: a critical mechanism in myeloma progression and therapy.

Multiple myeloma is a malignant hematopoietic neoplasm characterized by unclear molecular mechanisms and lack of highly effective targeted therapies for clinical application. Interferon regulatory factor 4 (IRF4) is a well-known core transcription factor that regulates the progression of myeloma, but the molecular mechanisms underlying its protein homeostasis regulation are unknown. Our research shows that lysosomal-associated membrane protein 5 (LAMP5) interacts with IRF4 and prevents its degradation through the autophagy-lysosome pathway, thereby facilitating the progression of myeloma. Addi