scholarly journals Recent Advances in Pharmacological Intervention of Osteoarthritis: A Biological Aspect

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinxia Deng ◽  
Zhixian Zong ◽  
Zhanpeng Su ◽  
Haicong Chen ◽  
Jianping Huang ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Bone Structure ◽  
Wide Spectrum ◽  
Biologic Agents ◽  
Joint Disease ◽  
Research Progress ◽  
Pharmacological Intervention ◽  
Special Technique ◽  
Biological Aspect ◽  
Rna Exosome

Osteoarthritis (OA) is a degenerative joint disease in the musculoskeletal system with a relatively high incidence and disability rate in the elderly. It is characterized by the degradation of articular cartilage, inflammation of the synovial membrane, and abnormal structure in the periarticular and subchondral bones. Although progress has been made in uncovering the molecular mechanism, the etiology of OA is still complicated and unclear. Nevertheless, there is no treatment method that can effectively prevent or reverse the deterioration of cartilage and bone structure. In recent years, in the field of pharmacology, research focus has shifted to disease prevention and early treatment rather than disease modification in OA. Biologic agents become more and more attractive as their direct or indirect intervention effects on the initiation or development of OA. In this review, we will discuss a wide spectrum of biologic agents ranging from DNA, noncoding RNA, exosome, platelet-rich plasma (PRP), to protein. We searched for key words such as OA, DNA, gene, RNA, exosome, PRP, protein, and so on. From the pharmacological aspect, stem cell therapy is a very special technique, which is not included in this review. The literatures ranging from January 2016 to August 2021 were included and summarized. In this review, we aim to help readers have a complete and precise understanding of the current pharmacological research progress in the intervention of OA from the biological aspect and provide an indication for the future translational studies.

scholarly journals Knockdown of long noncoding RNA HOTAIR inhibits osteoarthritis chondrocyte injury by miR-107/CXCL12 axis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jipeng Lu ◽  
Zhongxiong Wu ◽  
Ying Xiong
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
Cell Apoptosis ◽  
Noncoding Rna ◽  
Underlying Mechanism ◽  
Joint Disease ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Cxcl12 Expression ◽  
Ecm Degradation

Abstract Background Osteoarthritis (OA) is a joint disease characterized via destruction of cartilage. Chondrocyte damage is associated with cartilage destruction during OA. Long noncoding RNAs (lncRNAs) are implicated in the regulation of chondrocyte damage in OA progression. This study aims to investigate the role and underlying mechanism of lncRNA homeobox antisense intergenic RNA (HOTAIR) in OA chondrocyte injury. Methods Twenty-three OA patients and healthy controls without OA were recruited. Chondrocytes were isolated from OA cartilage tissues. HOTAIR, microRNA-107 (miR-107) and C-X-C motif chemokine ligand 12 (CXCL12) levels were measured by quantitative real-time polymerase chain reaction and western blot. Cell proliferation, apoptosis and extracellular matrix (ECM) degradation were measured using cell counting kit-8, flow cytometry and western blot. The target interaction was explored by bioinformatics, luciferase reporter and RNA immunoprecipitation assays. Results HOTAIR expression was enhanced, and miR-107 level was reduced in OA cartilage samples. HOTAIR overexpression inhibited cell proliferation, but induced cell apoptosis and ECM degradation in chondrocytes. HOTAIR knockdown caused an opposite effect. MiR-107 was sponged and inhibited via HOTAIR, and knockdown of miR-107 mitigated the effect of HOTAIR silence on chondrocyte injury. CXCL12 was targeted by miR-107. CXCL12 overexpression attenuated the roles of miR-107 overexpression or HOTAIR knockdown in the proliferation, apoptosis and ECM degradation. CXCL12 expression was decreased by HOTAIR silence, and restored by knockdown of miR-107. Conclusion HOTAIR knockdown promoted chondrocyte proliferation, but inhibited cell apoptosis and ECM degradation in OA chondrocytes by regulating the miR-107/CXCL12 axis.

Profile of Indian Patients with Juvenile Onset Chronic Inflammatory Joint Disease Using the ILAR Classification Criteria for JIA: A Community-based Cohort Study

2010 ◽  
Vol 37 (8) ◽  
pp. 1756-1762 ◽  
Author(s):  
VINAYA KUNJIR ◽  
ANURADHA VENUGOPALAN ◽  
ARVIND CHOPRA
Keyword(s):  
Wide Spectrum ◽  
Classification Criteria ◽  
Joint Disease ◽  
First Year ◽  
Hla B27 ◽  
Juvenile Onset ◽  
Rheumatology Clinic ◽  
American College Of Rheumatology ◽  
Indian Patients ◽  
Observational Cohort

Objective.To assess the current International League of Associations for Rheumatology (ILAR) classification criteria (Edmonton, 2001) for juvenile idiopathic arthritis (JIA) in Indian patients.Methods.Out of 441 children, 330 with chronic joint pains were diagnosed with juvenile onset chronic inflammatory arthritis and followed in an observational cohort. Our study was carried out from 1994 to 2006 in a community rheumatology clinic. Emphasis was placed on obtaining data required by the ILAR system. Of the original group, 235 children were eventually classified as having JIA; 108 were examined during the first year of illness.Results.We assigned 224 children (95%) to discrete JIA categories: enthesitis-related arthritis (ERA; 36%), oligoarthritis (OLA-persistent; 17%), polyarthritis rheumatoid factor (RF)-negative (17%), polyarthritis RF-positive (12%), systemic arthritis (8%), OLA-extended (4%), and psoriatic arthritis (1%). The remaining 11 children (5%) were classified with undifferentiated arthritis (mostly an overlap due to seropositive RF and/or HLA-B27). The prevalence of ERA (89% HLA-B27-positive) and seropositive RF was unexpectedly high. Although agreement (κ > 0.79) with the American College of Rheumatology criteria and the European Spondylarthropathy Study Group criteria was good to excellent, the ILAR system was found to be more comprehensive and clinically homogeneous. However, some problems appear unique in our scenario.Conclusion.A wide-spectrum phenotype of JIA is demonstrated by an Indian cohort. Although useful, RF and HLA-B27 in this population proved problematic to the ILAR classification.

scholarly journals Biological functions and clinical significance of long noncoding RNAs in bladder cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yan Zhang ◽  
Xianwu Chen ◽  
Juntao Lin ◽  
Xiaodong Jin
Keyword(s):  
Bladder Cancer ◽  
Clinical Significance ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Research Progress ◽  
High Morbidity ◽  
Biological Functions ◽  
Mesenchymal Transition

AbstractBladder cancer (BCa) is one of the 10 most common cancers with high morbidity and mortality worldwide. Long noncoding RNAs (lncRNAs), a large class of noncoding RNA transcripts, consist of more than 200 nucleotides and play a significant role in the regulation of molecular interactions and cellular pathways during the occurrence and development of various cancers. In recent years, with the rapid advancement of high-throughput gene sequencing technology, several differentially expressed lncRNAs have been discovered in BCa, and their functions have been proven to have an impact on BCa development, such as cell growth and proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and drug-resistance. Furthermore, evidence suggests that lncRNAs are significantly associated with BCa patients’ clinicopathological characteristics, especially tumor grade, TNM stage, and clinical progression stage. In addition, lncRNAs have the potential to more accurately predict BCa patient prognosis, suggesting their potential as diagnostic and prognostic biomarkers for BCa patients in the future. In this review, we briefly summarize and discuss recent research progress on BCa-associated lncRNAs, while focusing on their biological functions and mechanisms, clinical significance, and targeted therapy in BCa oncogenesis and malignant progression.

scholarly journals Gastric Aspiration and Its Role in Airway Inflammation

2018 ◽  
Vol 12 (1) ◽  
pp. 1-10 ◽  
Author(s):  
E.B. Hunt ◽  
A. Sullivan ◽  
J. Galvin ◽  
J. MacSharry ◽  
D.M. Murphy
Keyword(s):  
Wide Spectrum ◽  
Experimental Models ◽  
Clinical Syndrome ◽  
Pharmacological Intervention ◽  
Symptom Improvement ◽  
Gastric Aspiration ◽  
Airway Response ◽  
Clinical Benefits ◽  
The Individual ◽  
Chronic Airway

Gastro-Oesophageal Reflux (GOR) has been associated with chronic airway diseases while the passage of foreign matter into airways and lungs through aspiration has the potential to initiate a wide spectrum of pulmonary disorders. The clinical syndrome resulting from such aspiration will depend both on the quantity and nature of the aspirate as well as the individual host response. Aspiration of gastric fluids may cause damage to airway epithelium, not only because acidity is toxic to bronchial epithelial cells but also due to the effect of digestive enzymes such as pepsin and bile salts. Experimental models have shown that direct instillation of these factors to airways epithelia cause damage with a consequential inflammatory response. The pathophysiology of these responses is gradually being dissected, with better understanding of acute gastric aspiration injury, a major cause of acute lung injury, providing opportunities for therapeutic intervention and potentially, ultimately, improved understanding of the chronic airway response to aspiration. Ultimately, clarification of the inflammatory pathways which are related to micro-aspirationviapepsin and bile acid salts may eventually progress to pharmacological intervention and surgical studies to assess the clinical benefits of such therapies in driving symptom improvement or reducing disease progression.

scholarly journals Pharmacological Properties of Morus nigra L. (Black Mulberry) as A Promising Nutraceutical Resource

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 437 ◽  
Author(s):  
Sung Lim ◽  
Chang-Ik Choi
Keyword(s):  
Raw Materials ◽  
Wide Spectrum ◽  
Research Progress ◽  
Therapeutic Effects ◽  
Pharmacological Properties ◽  
Protective Effects ◽  
Anticancer Activities ◽  
Traditional Herbal Medicine ◽  
Morus Nigra ◽  
Silk Worm

Mulberry plants belonging to the Moraceae family have been grown for the purpose of being the nutrient source for silk worm and raw materials for the preparation of jams, marmalades, vinegars, juices, wines, and cosmetics. Morus nigra L. (black mulberry) is native to Southwestern Asia, and it has been used as a traditional herbal medicine for animals and humans. In this article, recent research progress on various biological and pharmacological properties of extracts, fractions, and isolated active constituents from different parts of M. nigra are reviewed. M. nigra exhibited a wide-spectrum of biological and pharmacological therapeutic effects including antinociceptive, anti-inflammatory, antimicrobial, anti-melanogenic, antidiabetic, anti-obesity, anti-hyperlipidemic, and anticancer activities. M. nigra also showed protective effects against various human organs and systems, mainly based on its antioxidant capacity. These findings strongly suggest that M. nigra can be used as a promising nutraceutical resource to control and prevent various chronic diseases.

Assessment of joint and bone structure in PsA patients: Using high-resolution computed tomography

2018 ◽  
Author(s):  
Camille Figueiredo ◽  
Georg Schett
Keyword(s):  
Computed Tomography ◽  
High Resolution ◽  
Bone Structure ◽  
Distinct Pattern ◽  
Bone Architecture ◽  
Joint Disease ◽  
High Resolution Computed Tomography ◽  
Bone Erosions ◽  
Bone Changes ◽  
Clinical Arthritis

Psoriatic arthritis (PsA) is associated with a distinct pattern of bone pathology, which influences the clinical picture of the disease. High-resolution computed tomography (CT) has contributed to understanding structural bone changes in PsA. Periarticular bone erosions in PsA are characterized by periosteal responses around the cortical break, distinguishing them from bone erosions in rheumatoid arthritis. Furthermore, a large number of enthesophytes can be found in CT studies of joints of PsA patients and in psoriasis patients without clinical arthritis. This latter observation supports the idea that articular changes start in psoriasis before joint disease commences. Moreover, enthesophytes are not influenced by methotrexate treatment and tumour necrosis factor inhibition. Finally, studies of systemic bone loss by high-resolution CT revealed significant alterations of the bone architecture in PsA but not in patients with skin disease only. In summary, CT has made valuable contributions in understanding the structural bone changes in PsA.

scholarly journals Pharmacological blood pressure control and outcomes in patients with hypertensive crisis discharged from the emergency department

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0251311
Author(s):  
Yu-Ting Lin ◽  
Yen-Hung Liu ◽  
Ya-Luan Hsiao ◽  
Hsiu-Yin Chiang ◽  
Pei-Shan Chen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Health Care ◽  
Emergency Department ◽  
Cardiovascular Mortality ◽  
Wide Spectrum ◽  
Hypertensive Crisis ◽  
Cox Proportional Hazards ◽  
Pharmacological Intervention ◽  
Care Utilization

Pharmacological blood pressure (BP) intervention for high blood pressure is controversial for a wide spectrum of hypertensive crisis in the emergency department (ED). We evaluated whether medical control of BP altered the short- and long-term outcomes among patients with hypertensive crisis who were discharged from the ED under universal health care. This retrospective cohort comprised 22 906 adults discharged from the ED of a tertiary hospital with initial systolic BP ≥ 180 mmHg or diastolic BP ≥ 120 mmHg between 2010 and 2016. The main exposure was the use of antihypertensive medication during the ED stay. Clinical endpoints were revisits to the ED or inpatient admission (at 7, 30, and 60 days), cardiovascular mortality (at 1, 3, and 5 years), and incident stroke (at 1, 3, and 5 years). The associations between pharmacological intervention for BP and outcomes were evaluated using multivariable Cox proportional-hazards models. Of the patient data analyzed, 72.2% were not treated pharmacologically and 68.4% underwent evaluation of end-organ damage. Pharmacological intervention for BP was significantly associated with a 11% and 11% reduced risk of hospital revisits within 30 or 60 days of discharge from ED, respectively, particularly among patients with polypharmacy. No association between pharmacological intervention for BP and incident stroke and cardiovascular mortality was observed. A revision of diagnostic criteria for hypertensive crisis is essential. Although pharmacological intervention for BP may not alter the long-term risk of cardiovascular mortality, it significantly reduces short-term health care utilization.

scholarly journals Targeting mutant p53 for cancer therapy: direct and indirect strategies

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jiahao Hu ◽  
Jiasheng Cao ◽  
Win Topatana ◽  
Sarun Juengpanich ◽  
Shijie Li ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Synthetic Lethality ◽  
Noncoding Rnas ◽  
Research Progress ◽  
Mutant P53 ◽  
Wild Type ◽  
Synthetic Lethal ◽  
Therapeutic Benefits ◽  
Synthetic Lethal Interactions ◽  
Wild Type P53

AbstractTP53 is a critical tumor-suppressor gene that is mutated in more than half of all human cancers. Mutations in TP53 not only impair its antitumor activity, but also confer mutant p53 protein oncogenic properties. The p53-targeted therapy approach began with the identification of compounds capable of restoring/reactivating wild-type p53 functions or eliminating mutant p53. Treatments that directly target mutant p53 are extremely structure and drug-species-dependent. Due to the mutation of wild-type p53, multiple survival pathways that are normally maintained by wild-type p53 are disrupted, necessitating the activation of compensatory genes or pathways to promote cancer cell survival. Additionally, because the oncogenic functions of mutant p53 contribute to cancer proliferation and metastasis, targeting the signaling pathways altered by p53 mutation appears to be an attractive strategy. Synthetic lethality implies that while disruption of either gene alone is permissible among two genes with synthetic lethal interactions, complete disruption of both genes results in cell death. Thus, rather than directly targeting p53, exploiting mutant p53 synthetic lethal genes may provide additional therapeutic benefits. Additionally, research progress on the functions of noncoding RNAs has made it clear that disrupting noncoding RNA networks has a favorable antitumor effect, supporting the hypothesis that targeting noncoding RNAs may have potential synthetic lethal effects in cancers with p53 mutations. The purpose of this review is to discuss treatments for cancers with mutant p53 that focus on directly targeting mutant p53, restoring wild-type functions, and exploiting synthetic lethal interactions with mutant p53. Additionally, the possibility of noncoding RNAs acting as synthetic lethal targets for mutant p53 will be discussed.

scholarly journals The Ambiguous Role of Microglia in Aβ Toxicity: Chances for Therapeutic Intervention

2020 ◽  
Vol 18 (5) ◽  
pp. 446-455 ◽  
Author(s):  
Sara Merlo ◽  
Simona Federica Spampinato ◽  
Grazia Ilaria Caruso ◽  
Maria Angela Sortino
Keyword(s):  
Disease Progression ◽  
Therapeutic Intervention ◽  
Microglial Activation ◽  
Wide Spectrum ◽  
Direct Interaction ◽  
Pharmacological Intervention ◽  
High Complexity ◽  
Regenerative Processes ◽  
Multiple Receptors

Amyloid-β (Aβ) has long been shown to be critical in Alzheimer’s disease pathophysiology. Microglia contributes to the earliest responses to Aβ buildup, by direct interaction through multiple receptors. Microglial cells operate Aβ clearance and trigger inflammatory/regenerative processes that take place in the long years of silent disease progression that precede symptomatic appearance. But in time and with aging, the fine balance between pro- and anti-inflammatory activity of microglia deranges, negatively impacting its Aβ-clearing ability. Furthermore, in recent years, microglial activation has proven to be much more complex than the mere dichotomic pro/antiinflammatory polarization previously accepted. Microglia can display a wide spectrum of phenotypes, which can even be mixed. On these bases, it is evident that while pharmacological intervention aiding microglia to prolong its ability to cope with Aβ buildup could be extremely relevant, its feasibility is hampered by such high complexity, which still needs to be completely understood.

scholarly journals Epigenetic Modulation on Tau Phosphorylation in Alzheimer’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Chao-Chao Yu ◽  
Tao Jiang ◽  
Ao-Fei Yang ◽  
Yan-Jun Du ◽  
Miao Wu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Noncoding Rna ◽  
Pathological Change ◽  
Epigenetic Modification ◽  
Tau Phosphorylation ◽  
Research Progress ◽  
Tau Hyperphosphorylation ◽  
Rna Regulation ◽  
Epigenetic Modulation

Tau hyperphosphorylation is a typical pathological change in Alzheimer’s disease (AD) and is involved in the early onset and progression of AD. Epigenetic modification refers to heritable alterations in gene expression that are not caused by direct changes in the DNA sequence of the gene. Epigenetic modifications, such as noncoding RNA regulation, DNA methylation, and histone modification, can directly or indirectly affect the regulation of tau phosphorylation, thereby participating in AD development and progression. This review summarizes the current research progress on the mechanisms of epigenetic modification associated with tau phosphorylation.

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