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Osteoporosis Diagnosis and Management: A Review from an Orthopedic Perspective.

Osteoporosis is a systemic skeletal disorder characterized by low bone density and microarchitectural deterioration, both of which lead to increased risk of fracture, disability, institutionalization, and mortality. Dual-energy X-ray absorptiometry (DEXA) remains the gold standard for evaluating bone mineral density and establishing diagnostic thresholds. However, accurate interpretation requires more than the application of numerical cut-offs. Interpretation requires careful evaluation of graphical bands, artifact recognition, awareness of site discordance, and application of least significan

Emerging Therapies in the Management of Advanced-Stage Gastric Cancer.

Globally, gastric malignancy contributes to significant cancer-related morbidity and mortality. Despite a recent approval of two targeted agents, trastuzumab and ramucirumab, the treatment options for advanced-stage gastric cancer are limited. Consequently, the overall clinical outcomes for patients with advanced-stage gastric cancer remain poor. Numerous agents that are active against novel targets have been evaluated in the course of randomized trials; however, most have produced disappointing results because of the molecular heterogeneity of gastric cancer. The Cancer Genome Atlas (TCGA) pr

Danshenol B alleviates central post-stroke pain by regulating the PIK3CG/NLRP3 signaling pathway.

BACKGROUND: Central post-stroke pain (CPSP) is a debilitating neuropathic condition that significantly impairs quality of life and is challenging to manage. Salvia miltiorrhiza (Danshen), a traditional Chinese herb, has demonstrated efficacy against neuropathic pain, but its active analgesic components and underlying mechanisms remain unclear. This study investigated the therapeutic potential of Danshenol B, an active component of Danshen, in a CPSP mouse model, focusing on its mechanism of action via the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (PIK3CG)/N

Systematic review and meta-analysis comparing zoledronic acid administered at 12-week and 4-week intervals in patients with bone metastasis.

Zoledronic acid is used to treat patients with bone metastasis, but the optimal dosing interval remains controversial. We therefore performed a systematic review and meta-analysis to compare the efficacy and safety of a 12-week interval of zoledronic acid with the standard 4-week interval. Three randomized controlled trials comprising 2650 patients were analyzed. Using a random-effects model, pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. No differences in the occurrence of skeletal-related events (SREs: RR = 0.98; 95% CI = 0.86-1.12; P = 0.80) or grade 3/4 advers

Drug resistance and tumor immune microenvironment: An overview of current understandings (Review).

The use of antitumor drugs represents a reliable strategy for cancer therapy. Unfortunately, drug resistance has become increasingly common and contributes to tumor metastasis and local recurrence. The tumor immune microenvironment (TME) consists of immune cells, cytokines and immunomodulators, and collectively they influence the response to treatment. Epigenetic changes including DNA methylation and histone modification, as well as increased drug exportation have been reported to contribute to the development of drug resistance in cancers. In the past few years, the majority of studies on tum

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Многоомичные биомаркеры, связанные с множественным склерозом: от менделианской случайности до прогнозирования наркотиков.

В настоящее время лечение и профилактика множественных склерозов (МС) по-прежнему сталкиваются с серьезными проблемами. Одним из важнейших методов проведения исследований в рамках реализации новых терапевтических стратегий стал менделийский анализ случайности (МСР). Соответственно, мы предполагаем, что существует причинно-следственная связь между генетическими вариантами конкретных плазменных белков и MS с помощью механизмов MR и что ключевые терапевтические цели можно точно определить путем интеграции многомерных аналитических подходов. В этом исследовании мы разработали всеобъемлющую аналити

Adoptive immune cell therapy for colorectal cancer.

Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality worldwide, with limited options for patients at advanced stages. Immunotherapy, particularly immune cell-based therapies, has gained significant attention as an innovative approach for targeting CRC. This review summarizes the progress in various immune cell therapies, including DC vaccine, CAR/TCR-T cells, CAR-NK cells et al, each engineered to recognize and attack cancer cells expressing specific antigens. CAR-T cell therapy, which has been successful in hematologic cancers, faces challenges in CRC due to the

The Hypoxia-Retinoid Axis in Idiopathic Pulmonary Fibrosis: Multifaceted Etiology and Therapeutic Potential.

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease with limited therapeutic options. This review focuses on the role of retinoids, particularly all-trans retinoic acid (atRA), and hypoxia in the pathogenesis of IPF. Despite an established understanding of genetic and environmental factors in IPF, the interplay between retinoid signaling and the response to hypoxia remains poorly explored due to its complexity. Preclinical evidence suggests that atRA could help reduce pulmonary fibrosis by modulating TGF-β signaling pathways and epithelial-to-mesenchymal transition (EM

Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination.

Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facilitation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro-oxidant than an anti-oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much highe

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… Fetuses without vitamin C in the brain have severe hemorrhages and there is apparently less collagen type IV in the basement membrane of brain vessels [ 69 , 70 ]. …

Investigation of the Effectiveness of Surgical Treatment on Maxillary Medication-Related Osteonecrosis of the Jaw: A Literature Review.

AIM: Medication-related osteonecrosis of the jaw (MRONJ) occurs after exposure to medication (antiresorptive or antiangiogenic agents) for bone-related complications. It is more common in the mandible than in the maxilla. The present study investigated maxillary MRONJ in elderly patients through a meta-analysis. METHODS: Keywords, including "MRONJ", "maxilla", and "surgery", were entered into databases, including Embase, PubMed/MEDLINE, Cochrane Library, and ProQuest, which were searched systematically. RESULTS: Investigating 77 studies, we found that 18 (2 case reports and 16 case series) p

Advances of HDAC inhibitors in tumor therapy: potential applications through immune modulation.

Histone deacetylase inhibitors (HDAC inhibitors, HDACi) have garnered considerable attention due to their potential in treating various types of malignant tumors. Histone deacetylases (HDACs) not only influence chromatin structure and gene transcription by regulating histone acetylation status but also acetylate various non-histone proteins. They are widely involved in several key biological processes, such as cell cycle regulation, apoptosis induction, and immune responses. HDACi exert their effects by inhibiting HDAC activity; however, these effects are highly concentration-dependent and non

Targeting fibrosis, mechanisms and cilinical trials.

Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response. Multiple organs can develop fibrosis, including the liver, kidney, heart, and lung. Fibrosis such as liver cirrhosis, idiopathic pulmonary fibrosis, and cystic fibrosis caused substantial disease burden. Persistent abnormal activation of myofibroblasts mediated by various signals, such as transforming growth factor, platelet-derived growth factor, and fibroblast growh factor, has been recongized as a major event in the occurrence and progression of fibrosi

Circulating biosignatures in multiple myeloma and their role in multidrug resistance.

A major obstacle to chemotherapeutic success in cancer treatment is the development of drug resistance. This occurs when a tumour fails to reduce in size after treatment or when there is clinical relapse after an initial positive response to treatment. A unique and serious type of resistance is multidrug resistance (MDR). MDR causes the simultaneous cross resistance to unrelated drugs used in chemotherapy. MDR can be acquired through genetic alterations following drug exposure, or as discovered by us, through alternative pathways mediated by the transfer of functional MDR proteins and nucleic

Efficacy of Danshen injection combined with Calcitriol and Calcium/Vitamin-D for the treatment of osteoporotic fractures: A retrospective case-control study.

ObjectiveTo explore the efficacy of Danshen injection combined with calcitriol and calcium/Vitamin-D in the treatment of osteoporotic fractures.MethodsThis was a case-control study. We retrospectively reviewed clinical data of 91 patients with osteoporotic fractures who received treatment in Rui'an People's Hospital from February 2021 to July 2022. The data were divided into a control group with 44 records of patients who received treatment with calcitriol and calcium/Vitamin-D, and a study group with 47 patients who received Danshen injection combined with calcitriol and calcium/Vitamin-D. Th

Bone-modifying therapy in multiple myeloma: a comprehensive review.

Multiple myeloma (MM) is a clonal hematologic malignancy characterized by plasma cell proliferation in the bone marrow. One of the most common clinical presentations is skeletal-related events (SREs), characterized by osteolysis of the bone, leading to a significant morbidity and mortality. The main aim of this review article is to provide an overview of the pathogenesis and evidence-based, guideline-recommended treatment of SREs. MM bone homeostasis is altered by numerous pathways and cytokines, leading to the pathogenesis of bone and osteolytic lesions. Historically, bisphosphonates were the

Utilizing 3D Models to Unravel the Dynamics of Myeloma Plasma Cells' Escape from the Bone Marrow Microenvironment.

Recent therapeutic advancements have markedly increased the survival rates of individuals with multiple myeloma (MM), doubling survival compared to pre-2000 estimates. This progress, driven by highly effective novel agents, suggests a growing population of MM survivors exceeding the 10-year mark post-diagnosis. However, contemporary clinical observations indicate potential trends toward more aggressive relapse phenotypes, characterized by extramedullary disease and dominant proliferative clones, despite these highly effective treatments. To build upon these advances, it is crucial to develop m

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… . | [ 58 , 62 , 63 ] Hydrogel | MM cells | Matrigel, Fibronectin, and Collagen Type IV | 6 days | Modelled the endosteum–MM interaction. Activation of STAT3 was observed in 3D cells but not in 2D cells. | Utilised MM cell lines. …

Transformative Impact of Nanocarrier-Mediated Drug Delivery: Overcoming Biological Barriers and Expanding Therapeutic Horizons.

Advancing therapeutic progress is centered on developing drug delivery systems (DDS) that control therapeutic molecule release, ensuring precise targeting and optimal concentrations. Targeted DDS enhances treatment efficacy and minimizes off-target effects, but struggles with drug degradation. Over the last three decades, nanopharmaceuticals have evolved from laboratory concepts into clinical products, highlighting the profound impact of nanotechnology in medicine. Despite advancements, the effective delivery of therapeutics remains challenging because of biological barriers. Nanocarriers offe

Current options for the treatment of Paget's disease of the bone.

Paget's disease of bone (PDB) is a chronic bone remodelling disorder characterized by increased osteoclast-mediated bone resorption, with subsequent compensatory increases in new bone formation, resulting in a disorganized mosaic of woven and lamellar bone at affected skeletal sites. This disease is most often asymptomatic but can be associated with bone pain or deformity, fractures, secondary arthritis, neurological complications, deafness, contributing to substantial morbidity and reduced quality of life. Neoplastic degeneration of pagetic bone is a relatively rare event, occurring with an i

Изучение точных методов лечения иммунизированных подстрекательских заболеваний: использование бесконечного потенциала доставки нуклеиновой кислоты.

Неизлечимые подстрекательские заболевания (ИМИД) создают неизмеримое бремя для отдельных лиц и общества. В то время как традиционное использование иммунодепрессантов и лекарственных средств для борьбы с заболеваниями обеспечивает частичную помощь и контроль, их неизбежные побочные эффекты и ограниченная эффективность ставят под сомнение возможность найти лекарство. Перспективные лекарства от нуклеиновой кислоты продемонстрировали способность оказывать точное воздействие на молекулярном уровне, при этом различные классы нуклеиновых кислот выполняют регулирующие функции с помощью различных механ