Dual-Ligand Ruthenium Coordination Polymer-Derived Self-Enhanced Electrochemiluminescent Emitters for Sensitive Detection of Procalcitonin.

Ru-based electrochemiluminescence (ECL) coordination polymers are widely employed for bioanalysis and medical diagnosis. However, commonly used Ru-based coordination polymers face the limitation of low efficiency due to the long distance between the ECL reagent and the coreactant dispersed in detecting solution. Herein, we report a dual-ligand self-enhanced ECL coordination polymer, composed of tris(4,4'-dicarboxylic acid-2,2'-bipyridyl) ruthenium(II) dichloride (Ru(dcbpy)32+) as ECL reactant ligand and ethylenediamine (EDA) as corresponding coreactant ligand into Zn2+ metal node, termed Zn-Ru-EDA. Zn-Ru-EDA shows excellent ECL performance which is attributed to the effective intramolecular electron transport between the two ligands. Furthermore, the dual-ligand polymer allows an anodic low excitation potential (+1.09 V) luminescence. The shift in the energy level of the highest occupied molecular orbital (HOMO) upward after the synthesis of the Zn-Ru-EDA has resulted in a reduced excitation potential. The low excitation potential reduced biomolecular damage and the destruction of the modified electrodes. The ECL biosensor has been constructed using Zn-Ru-EDA with high ECL efficiency for the ultrasensitive detection of a bacterial infection and sepsis biomarker, procalcitonin (PCT), in the range from 1.00 × 10-6 to 1.00 × 10 ng·mL-1 with outstanding selectivity, and the detection limit was as low as 0.47 fg·mL-1. Collectively, the dual-ligand-based self-enhanced polymer may provide an ideal strategy for high ECL efficiency improvement as well as designing new self-enhanced multiple-ligand-based coordination in sensitive biomolecular detection for early disease diagnostics.

Synthesis and evaluation of the cell cycle arrest and CT DNA interaction properties of 4ß-amino-4'-O-demethyl-4-deoxypodophyllotoxins.

A series of 4ß-amino-4'-O-demethyl-4-deoxypodophyllotoxin derivatives were synthesized, and their cytotoxicities against several human cancer cell lines, including HepG2, A549, HeLa and HCT-8 cells, evaluated. Some of these compounds exhibited higher levels of cytotoxicity than the anticancer drug etoposide. 4ß-N-(4-Nitrophenyl piperazinyl)-4'-O-demethyl-4-deoxypodophyllotoxin (11) was found to be the most potent synthesized compound in the current study, and induced cell cycle arrest in the G2/M phase in HeLa cells, which was accompanied by apoptosis. Furthermore, this compound activated the expression of cdc2, cyclin B1, p53 and caspase-3 in HeLa cells, leading to changes in the conformation of calf thymus DNA from the B-form to a more compact C-form.

(4-Chlorobenzoyl)(4-chlorophenyl)amino 3-(2-nitrophenyl)propanoate.

In the title hydroxamic acid derivate, C22H16Cl2N2O5, the nitro-substituted benzene ring forms dihedral angles of 14.11 (15) and 16.08 (15)°, with the 4-chloro-benzoyl and 4-chloro-phenyl benzene rings, respectively. The dihedral angle between the chloro-substituted benzene rings is 2.28 (13)°. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, forming chains along [100].

Unlocking the Potential: Amino Acids' Role in Predicting and Exploring Therapeutic Avenues for Type 2 Diabetes Mellitus.

Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), imposes a significant global burden with adverse clinical outcomes and escalating healthcare expenditures. Early identification of biomarkers can facilitate better screening, earlier diagnosis, and the prevention of diabetes. However, current clinical predictors often fail to detect abnormalities during the prediabetic state. Emerging studies have identified specific amino acids as potential biomarkers for predicting the onset and progression of diabetes. Understanding the underlying pathophysiological mechanisms can offer valuable insights into disease prevention and therapeutic interventions. This review provides a comprehensive summary of evidence supporting the use of amino acids and metabolites as clinical biomarkers for insulin resistance and diabetes. We discuss promising combinations of amino acids, including branched-chain amino acids, aromatic amino acids, glycine, asparagine and aspartate, in the prediction of T2DM. Furthermore, we delve into the mechanisms involving various signaling pathways and the metabolism underlying the role of amino acids in disease development. Finally, we highlight the potential of targeting predictive amino acids for preventive and therapeutic interventions, aiming to inspire further clinical investigations and mitigate the progression of T2DM, particularly in the prediabetic stage.

Fighting age-related orthopedic diseases: focusing on ferroptosis.

Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It is closely related to multiple biological processes, including iron metabolism, polyunsaturated fatty acid metabolism, and the biosynthesis of compounds with antioxidant activities, including glutathione. In the past 10 years, increasing evidence has indicated a potentially strong relationship between ferroptosis and the onset and progression of age-related orthopedic diseases, such as osteoporosis and osteoarthritis. Therefore, in-depth knowledge of the regulatory mechanisms of ferroptosis in age-related orthopedic diseases may help improve disease treatment and prevention. This review provides an overview of recent research on ferroptosis and its influences on bone and cartilage homeostasis. It begins with a brief overview of systemic iron metabolism and ferroptosis, particularly the potential mechanisms of ferroptosis. It presents a discussion on the role of ferroptosis in age-related orthopedic diseases, including promotion of bone loss and cartilage degradation and the inhibition of osteogenesis. Finally, it focuses on the future of targeting ferroptosis to treat age-related orthopedic diseases with the intention of inspiring further clinical research and the development of therapeutic strategies.

Surgical treatment of patellar dislocation: A network meta-analysis of randomized control trials and cohort studies.

Background: Currently, there are many surgical options for patellar dislocation. The purpose of this study is to perform a network meta-analysis of the randomized controlled trials (RCTs) and cohort studies to determine the better treatment. Method: We searched the Pubmed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, clinicaltrials.gov and who.int/trialsearch. Clinical outcomes included Kujala score, Lysholm score, International Knee Documentation Committee (IKDC) score, redislocation or recurrent instability. We conducted pairwise meta-analysis and network meta-analysis respectively using the frequentist model to compare the clinical outcomes. Results: There were 10 RCTs and 2 cohort studies with a total of 774 patients included in our study. In network meta-analysis, double-bundle medial patellofemoral ligament reconstruction (DB-MPFLR) achieved good results on functional scores. According to the surface under the cumulative ranking (SUCRA), DB-MPFLR had the highest probabilities of their protective effects on outcomes of Kujala score (SUCRA 96.5 %), IKDC score (SUCRA 100.0%) and redislocation (SUCRA 67.8%). However, DB-MPFLR (SUCRA 84.6%) comes second to SB-MPFLR (SUCRA 90.4%) in Lyshlom score. It is (SUCRA 70%) also inferior to vastus medialis plasty (VM-plasty) (SUCRA 81.9%) in preventing Recurrent instability. The results of subgroup analysis were similar. Conclusion: Our study demonstrated that MPFLR showed better functional scores than other surgical options.

Endoplasmic Reticulum Stress in Osteoarthritis: A Novel Perspective on the Pathogenesis and Treatment.

Osteoarthritis (OA), the most common degenerative joint disease, causes an enormous socioeconomic burden due to its disabling properties and high prevalence. Increasing evidence suggests that OA is a whole-joint disease involving cartilage degradation, synovitis, meniscal lesions, and subchondral bone remodeling. Endoplasmic reticulum (ER) stress is the accumulation of misfolded/unfolded proteins in the ER. Recent studies have found that ER stress is involved in the OA pathological changes by influencing the physiological function and survival of chondrocytes, fibroblast-like synoviocytes, synovial macrophages, meniscus cells, osteoblasts, osteoclasts, osteocytes, and bone marrow mesenchymal stem cells. Therefore, ER stress is an attractive and promising target for OA. However, although targeting ER stress has been proven to alleviate OA progression in vitro and in vivo, the treatments for OA remain in preclinical stage and require further investigation.

A Worldwide Bibliometric Analysis of Tetrandrine Research in Recent Two Decades.

Background: Tetrandrine has been the focus of many studies in recent years. Currently, no bibliometric study in this field has been published. This study presents a bibliometric analysis of the articles on tetrandrine research from the WOS core database during the recent two decades. Methods: Documents were retrieved for further bibliometric analysis based on the search terms: [TI = (Tetrandrine OR Sinomeninea OR Hanfangchin A) AND PY = (2000-2021)]. We used Microsoft Excel to conduct the frequency analysis, VOSviewer for data visualization, and RStudio for citation metrics and analysis. The standard bibliometric indicators such as the temporal trends and geographical distribution of publications and citations, prolific authors and co-authorship, keywords citation burst, preferred journals, top-cited articles, and important institutions were applied in this study. Results: 490 documents were retrieved from WOS core database, the retrieved document type consists of 8 categories: 425 articles, 42 meeting abstracts, 8 reviews, 7 corrections, 3 editorial material, 2 proceedings paper, 1 letter, 1 retraction. Corrections and Retractions was excluded from this investigation, the left 482 document were included for furter bibliometric analysis. Conclusion: Based on our findings, there was a continuous growth of publications on tetrandrine research for 22 years since 2000. China was the largest contributor to tetrandrine research, followed by the United States. The most influential author was Cheng Y (Natl Taiwan Univ Hosp). Acta Pharmacol Sin remained the main publication related to tetrandrine research. Chinese Academy of Sciences, is expected to be a good collaborating center in tetrandrine research. The use of tetrandrine in cancer treatment, could be the promising research subject areas to follow.

Inhibition of PGE2 in Subchondral Bone Attenuates Osteoarthritis.

Aberrant subchondral bone architecture is a crucial driver of the pathological progression of osteoarthritis, coupled with increased sensory innervation. The sensory PGE2/EP4 pathway is involved in the regulation of bone mass accrual by the induction of differentiation of mesenchymal stromal cells. This study aimed to clarify whether the sensory PGE2/EP4 pathway induces aberrant structural alteration of subchondral bone in osteoarthritis. Destabilization of the medial meniscus (DMM) using a mouse model was combined with three approaches: the treatment of celecoxib, capsaicin, and sensory nerve-specific prostaglandin E2 receptor 4 (EP4)-knockout mice. Cartilage degeneration, subchondral bone architecture, PGE2 levels, distribution of sensory nerves, the number of osteoprogenitors, and pain-related behavior in DMM mice were assessed. Serum and tissue PGE2 levels and subchondral bone architecture in a human sample were measured. Increased PGE2 is closely related to subchondral bone's abnormal microstructure in humans and mice. Elevated PGE2 concentration in subchondral bone that is mainly derived from osteoblasts occurs in early-stage osteoarthritis, preceding articular cartilage degeneration in mice. The decreased PGE2 levels by the celecoxib or sensory denervation by capsaicin attenuate the aberrant alteration of subchondral bone architecture, joint degeneration, and pain. Selective EP4 receptor knockout of the sensory nerve attenuates the aberrant formation of subchondral bone and facilitates the prevention of cartilage degeneration in DMM mice. Excessive PGE2 in subchondral bone caused a pathological alteration to subchondral bone in osteoarthritis and maintaining the physiological level of PGE2 could potentially be used as an osteoarthritis treatment.

A worldwide bibliometric analysis of triptolide research from 1997 to 2021.

OBJECTIVES: In recent years, triptolide has received much attention due to its wide range of pharmacological activities. However, no bibliometric studies have been published on triptolide. This study conducted a bibliometric study to provide scientific and insightful information for further research. METHODS: This study performed a bibliometric study of articles published in the Web of Science database from 1997 to 2021. Based on the keywords used in relation to the title of the article containing the word triptolide, 970 publications were searched for further analysis. We used Microsoft Excel for frequency analysis, VOSviewer and CiteSpace for data visualization, and Rstudio for citation metrics and analysis. RESULTS: After analysis, standard bibliometric indicators such as the growth of publications, prolific authors and coauthorship, country distributions, preferred journals, most influential institutions and top cited documents were presented in this study. CONCLUSIONS: According to our findings, the number of triptolide-related publications has been increasing since 2009. China was the largest contributor to triptolide research, followed by the USA. Biomedicine & Pharmacotherapy was the leading journal related to triptolide research. The most productive authors were Zhang LY (China Pharmaceut Univ) and Jiang ZZ (China Pharmaceut Univ). China Pharmaceutical University was the most influential institution in the field of triptolide research. Our findings suggest that the effective use of triptolide in cancer therapy as well as overcoming its multiorgan toxicity to promote its widespread clinical applications are expected to be hot research topics in the future.

The top 100 most-cited articles on exercise therapy for sarcopenia: A bibliometric analysis.

Objective: Vast quantities of literature regarding the applications of exercise therapy for sarcopenia have been published. The main objective of this study is to determine the top 100 most-cited articles and analyze their bibliometric characteristics. Design: This study reports a bibliometric analysis via a systematic search of the academic literature regarding the applications of exercise therapy for sarcopenia. Methods: All databases in the Web of Science were searched with the following strategy: term search (TS) = (exercise* OR training OR "physical activit*") AND TS = (sarcopenia) on 25 February 2022. The results were presented in descending order by their total citations. The list of the top 100 articles was finally determined by negotiation of two independent researchers. Results: The top 100 articles were published between 1993 and 2020. More than half of the articles (n = 54) were published during the decade 2006-2015. Total citations of the top 100 articles ranged from 155 to 1,131 with a median of 211.5. The average of annual citations was constantly increasing with year (P < 0.05). The most studied exercise therapy is strength/resistance training, with about 71% articles had discussed about it. The top 100 articles were from 54 different journals, and the Journal of Applied Physiology was the journal that contributed the most articles (n = 8). A total of 75 different first corresponding authors from 15 countries made contributions to the top 100 list. Luc J.C. van Loon from the Maastricht University in the Netherlands published the most articles (n = 5) as the first corresponding author. Most articles (87%) were from North America (58%) and Europe (29%), while the United States as a country contributed over half of the articles (51%). Conclusion: Our study determined the top 100 most-cited articles on exercise therapy for sarcopenia and analyzed their bibliometric characteristics, which may provide a recommended list for researchers in this field and pave the way for further research.

Arthroscopic therapy of rotator cuff diseases: A bibliometric study of the past 2 decades (2002-2021).

Purpose: Rotator cuff diseases, as a common cause of shoulder pain and disability, have seriously affected the patients' daily life. Rotator cuff repair techniques have been a hot topic in the arthroscopic therapy field. Our study was to use bibliometrics analysis to clarify the current status and research trends in the field of arthroscopic therapy of rotator cuff diseases. Methods: The publications relating to arthroscopic therapy of rotator cuff diseases published from 2001 to 2021 were obtained from the Web of Science Core Collection (WoSCC) database. The R software and VOSviewer software were used for the cross-sectional bibliometric and scientometric analysis. Results: A total of 4,567 publications about arthroscopic therapy of rotator cuff diseases published between 2002 and 2021 retrieved from the WoSCC database were analyzed in our study. The results showed that the United States made the largest contribution to this field. The most relevant institutions were Seoul National University, Rush University, and Hospital for Special Surgery. Stephen S Burkhart was the most relevant researcher in this field with the largest number of publications, as well as the highest H-index and G-index. The journal ARTHROSCOPY contributed the largest number of publications in the past 2 decades. Considering the H-index and G-index, ARTHROSCOPY was also the journal with the largest impact in this field. Conclusions: Arthroscopic Therapy of Rotator Cuff Diseases Related research presented a rising trend in the past 2 decades. The United States can be regarded as the leader because of its huge contributions to this field. The journal ARTHROSCOPY published the largest number of publications in this field. It can be predicted that research about advanced arthroscopic techniques and postoperative pain management of patients with rotator cuff diseases will be the next research hotspots in the following years.

Exosomes in osteoarthritis: Updated insights on pathogenesis, diagnosis, and treatment.

Osteoarthritis (OA) has remained a prevalent public health problem worldwide over the past decades. OA is a global challenge because its specific pathogenesis is unclear, and no effective disease-modifying drugs are currently available. Exosomes are small and single-membrane vesicles secreted via the formation of endocytic vesicles and multivesicular bodies (MVBs), which are eventually released when MVBs fuse with the plasma membrane. Exosomes contain various integral surface proteins derived from cells, intercellular proteins, DNAs, RNAs, amino acids, and metabolites. By transferring complex constituents and promoting macrophages to generate chemokines and proinflammatory cytokines, exosomes function in pathophysiological processes in OA, including local inflammation, cartilage calcification and degradation of osteoarthritic joints. Exosomes are also detected in synovial fluid and plasma, and their levels continuously change with OA progression. Thus, exosomes, specifically exosomal miRNAs and lncRNAs, potentially represent multicomponent diagnostic biomarkers for OA. Exosomes derived from various types of mesenchymal stem cells and other cell or tissue types affect angiogenesis, inflammation, and bone remodeling. These exosomes exhibit promising capabilities to restore OA cartilage, attenuate inflammation, and balance cartilage matrix formation and degradation, thus demonstrating therapeutic potential in OA. In combination with biocompatible and highly adhesive materials, such as hydrogels and cryogels, exosomes may facilitate cartilage tissue engineering therapies for OA. Based on numerous recent studies, we summarized the latent mechanisms and clinical value of exosomes in OA in this review.

Synthesis and biological evaluation of conjugates of deoxypodophyllotoxin and 5-FU as inducer of caspase-3 and -7.

In order to generate compounds with superior antitumor activity and reduced toxicity, a series of conjugates of deoxypodophyllotoxin and 5-FU were synthesized by coupling 4'-demethyl-4-dexoypodophyllotoxin with N-(5-fluorouracil-N(1)-ly acetic)- amino acids (or 5-fluorouracil-N(1)-ly acetic acid). The cytotoxic activity of these compounds against four human cancer cell lines (HL-60, A-549, HeLa and SiHa) were evaluated, and results indicated that these compounds were more potent in terms of cytotoxicity than either parent compound DPT or anticancer drug VP-16 and 5-FU. In addition, we found that 14d induced cell cycle arrest in the G2/M phase accompanied by apoptosis in A-549 cells, and 14d activated caspase-3 and -7. These results suggested that caspase-mediated pathways are involved in 14d induced apoptosis.