Local corticosteroid injection versus physical therapy for the treatment of carpal tunnel syndrome: A systematic review and meta-analysis of randomized controlled trials.

The comparative effect of commonly used conservative treatments for carpal tunnel syndrome remained controversial. The purpose of this study was to compare the clinical effect of local corticosteroid injection and physical therapy for the treatment of carpal tunnel syndrome. A systematic literature search of PubMed, EMBASE, and Cochrane library was conducted to identify relevant randomized clinical trials published before 21st Mar 2023. Two independent reviewers assayed quality of included studies using the Cochrane collaboration risk of bias tool. Relevant data were extracted and pooled analyses were conducted. Outcome measurements included Boston Carpal Tunnel Syndrome Questionnaire, visual analogue scale and some electrophysiology tests, while the former two were set as the primary outcomes. Subgroup analysis and sensitive analysis were performed and publication bias was evaluated. Heterogeneity among the included studies was examined using the I2 statistic. After selection, 12 studies were identified eligibility for inclusion. Only one study was found to have a high risk of bias. Pooled data of primary outcomes did not show any differences between treatments, and subgroup analysis supported the results. However, patients treated with local corticosteroid injection showed better improvement in distal motor latency (p = 0.002) and compound muscle action potential (p = 0.04). Some studies failed to pass the sensitive analysis, indicating the related analysis might be not so stable. A slight publication bias was observed in subgroup analysis of function scales, among three publication bias test. In conclusion, compared to physical therapy, local corticosteroid injection might have better treatment effects on carpal tunnel syndrome.

Current Status and Trends of Research on Anthracycline-Induced Cardiotoxicity from 2002 to 2021: A Twenty-Year Bibliometric and Visualization Analysis.

Anthracyclines constitute the cornerstone of numerous chemotherapy regimens for various cancers. However, the clinical application of anthracyclines is significantly limited to their dose-dependent cardiotoxicity. A comprehensive understanding of the current status of anthracycline-induced cardiotoxicity is necessary for in-depth research and optimal clinical protocols. Bibliometric analysis is widely applied in depicting development trends and tracking frontiers of a specific field. The present study is aimed at revealing the status and trends of anthracycline-induced cardiotoxicity during the past two decades by employing bibliometric software including R-bibliometric, VOSviewer, and CiteSpace. A total of 3504 publications concerning anthracycline-induced cardiotoxicity from 2002 to 2021 were collected from the Web of Science Core Collection database. Results showed significant growth in annual yields from 90 records in 2002 to 304 papers in 2021. The United States was the most productive country with the strongest collaboration worldwide in the field. Charles University in the Czech Republic was the institution that contributed the most papers, while 7 of the top 10 productive institutions were from the United States. The United States Department of Health and Human Services and the National Institutes of Health are the two agencies that provide financial support for more than 50% of sponsored publications. The research categories of included publications mainly belong to Oncology and Cardiac Cardiovascular Systems. The Journal of Clinical Oncology had a comprehensive impact on this research field with the highest IF value and many publications. Simunek Tomas from Charles University contributed the most publications, while Lipshultz Steven E. from the State University of New York possessed the highest H-index. In addition, the future research frontiers of anthracycline-induced cardiotoxicity might include early detection, pharmacogenomics, molecular mechanism, and cardiooncology. The present bibliometric analysis may provide a valuable reference for researchers and practitioners in future research directions.

Pretreatment with resveratrol ameliorate trigeminal neuralgia by suppressing matrix metalloproteinase-9/2 in trigeminal ganglion.

Trigeminal neuralgia (TN) is a common type of neuropathic pain whereas the underlying pathogenesis has not been completely elucidated. Recent study suggests that the development of neuroinflammation is responsible for generating and sustaining neuropathic pain. The purpose of our study was to investigate the protective effect of intervening the inflammation in early stages of pain and explore its potential mechanism. MMP-9 and MMP-2 are vital proinflammatory participants and accumulating evidence indicates that they are involved in the early development of neuropathic pain. In this study, we found that MMP-9/2 showed different temporal up regulation in trigeminal ganglion (TG) significantly after chronic constriction injury (CCI) surgery. However, the activation of MMP-9/2 were suppressed by the pretreatment with resveratrol, which delayed and attenuated CCI-induced mechanical allodynia simultaneously. Besides, the expression of proinflammatory cytokines like IL-1ß and TNF-α as well as the excessive neuronal activity induced by CCI were suppressed by resveratrol. Moreover, we believed that the inhibition of MMP-9/2 activation and pain sensitization may be related to the TLR-4/NF-κB signaling pathway, which might be negatively regulated by the induction of SOCS3. In conclusion, pretreatment with resveratrol could be an effective approach to alleviate trigeminal neuralgia in early stages via a powerful inhibition on the activation of MMP-9/2 in TG.

Ligand-induced activation of ERK1/2 signaling by constitutively active Gs-coupled 5-HT receptors.

5-HT4R, 5-HT6R, and 5-HT7AR are three constitutively active Gs-coupled 5-HT receptors that have key roles in brain development, learning, memory, cognition, and other physiological processes in the central nervous system. In addition to Gs signaling cascade mediated by these three 5-HT receptors, the ERK1/2 signaling which is dependent on cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) activation downstream of Gs signaling has also been widely studied. In this study, we investigated these two signaling pathways originating from the three Gs-coupled 5-HT receptors in AD293 cells. We found that the phosphorylation and activation of ERK1/2 are ligand-induced, in contrast to the constitutively active Gs signaling. This indicates that Gs signaling alone is not sufficient for ERK1/2 activation in these three 5-HT receptors. In addition to Gs, we found that ß-arrestin and Fyn are essential for the activation of ERK1/2. Together, these results put forth a novel mechanism for ERK1/2 activation involving the cooperative action of Gs, ß-arrestin, and Fyn.

[Correlation of the single nucleotide polymorphisms rs34349826 and rs6521 of the LHB gene with male infertility in Chinese men].

Objective: To study the relationship of the single nucleotide polymorphisms (SNP) rs34349826 (c.104 A>G) and rs6521 (c.114 C>G) of the luteinizing hormone beta-subunit (LHB) gene with male infertility in Chinese men. METHODS: This case-control study included 405 males with primary infertility (the infertility group) and 424 normal fertile men (the control group), the former again divided into subgroups of oligospermia, severe oligozoospermia and azoospermia according to the sperm concentration. Clinical data were collected from all the subjects and genomic DNA obtained from their peripheral blood for genotyping rs34349826 and rs6521 of the LHB gene by Sequence MassArray. We analyzed the correlation of male infertility with the SNPs of the two loci using the logistic regression model as well as its association with their haplotype combination with the SHEsis online software. RESULTS: There were statistically significant differences between the control and infertility groups in the semen volume (ï¼»3.51 ± 1.36ï¼½ vs ï¼»3.74 ± 1.71ï¼½ ml, P <0.05), sperm concentration (ï¼»79.21 ± 61.60ï¼½ vs ï¼»27.37 ± 30.80ï¼½ ×106/ml, P <0.01), percentage of progressively motile sperm (ï¼»39.40 ± 9.64ï¼½ % vs ï¼»11.90 ± 14.72ï¼½ %, P <0.01), and levels of serum luteinizing hormone (LH) (ï¼»3.29 ± 1.39ï¼½ vs ï¼»6.25 ± 4.83ï¼½ IU/L, P <0.01) and follicle-stimulating hormone (FSH) (ï¼»4.56 ± 2.31ï¼½ vs ï¼»15.64 ± 17.03ï¼½ IU/L, P <0.01). Logistic regression analysis revealed no correlation between male infertility and the genotypes of the rs34349826 and rs6521 loci of the LHB gene, and similar results were found in the subgroups of the infertile males. SHEsis analysis on the haplotypes of the rs34349826 and rs6521 loci showed the GG genotype combination to be a protective factor against male infertility. CONCLUSIONS: The rs34349826 and rs6521 loci of the LHB gene were not related to male infertility, which can be further confirmed by larger-sample studies. The GG genotype combination is a protective factor against male infertility.

Protective Effects of Fucoidan on Aß25-35 and d-Gal-Induced Neurotoxicity in PC12 Cells and d-Gal-Induced Cognitive Dysfunction in Mice.

Alzheimer's disease (AD) is a chronic neurodegenerative disease which contributes to memory loss and cognitive decline in the elderly. Fucoidan, extracted from brown algae, is a complex sulfated polysaccharide and potential bioactive compound. In this study, we investigated whether fucoidan protects PC12 cells from apoptosis induced by a combination of beta-amyloid 25-35 (Aß25-35) and d-galactose (d-Gal), and improves learning and memory impairment in AD model mice. The results indicated that fucoidan could inhibit the release of cytochrome c from the mitochondria to cytosol and activation of caspases, and increase the expression of apoptosis inhibitor proteins (IAPs), including livin and X-linked IAP (XIAP) in PC12 cells damaged by Aß25-35 and d-Gal-induction. Fucoidan reversed the decreased activity of acetylcholine (ACh) and choline acetyl transferase (ChAT), as well as the increased activity of acetylcholine esterase (AChE), in AD model mice induced by infusion of d-Gal. Furthermore, fucoidan improved antioxidant activity in vitro and in vivo by activation of superoxide dismutase (SOD) and glutathione (GSH). These results suggested that fucoidan could protect PC12 cells from apoptosis and ameliorate the learning and memory impairment in AD model mice, which appeared to be due to regulating the cholinergic system, reducing oxidative stress, and inhibiting the caspase-dependent apoptosis pathway.

Identification and biochemical characterization of DC07090 as a novel potent small molecule inhibitor against human enterovirus 71 3C protease by structure-based virtual screening.

Hand, foot and mouth disease (HFMD) is a serious, highly contagious disease. HFMD caused by Enterovirus 71 (EV71), results in severe complications and even death. The pivotal role of EV71 3Cpro in the viral life cycle makes it an attractive target for drug discovery and development to treat HFMD. In this study, we identified novel EV71 3Cpro inhibitors by docking-based virtual screening. Totally 50 compounds were selected to test their inhibitory activity against EV71 3Cpro. The best inhibitor DC07090 exhibited the inhibition potency with an IC50 value of 21.72 ± 0.95 µM without apparent toxicity (CC50 > 200 µM). To explore structure-activity relationship of DC07090, 15 new derivatives were designed, synthesized and evaluated in vitro enzyme assay accordingly. Interestingly, four compounds showed inhibitory activities against EV71 3Cpro and only DC07090 inhibited EV71 replication with an EC50 value of 22.09 ± 1.07 µM. Enzyme inhibition kinetic experiments showed that the compound was a reversible and competitive inhibitor. The Ki value was determined to be 23.29 ± 12.08 µM. Further molecular docking, MD simulation and mutagenesis studies confirmed the binding mode of DC07090 and EV71 3Cpro. Besides, DC07090 could also inhibit coxsackievirus A16 (CVA16) replication with an EC50 value of 27.76 ± 0.88 µM. Therefore, DC07090 represents a new non-peptidyl small molecule inhibitor for further development of antiviral therapy against EV71 or other picornaviruses.

Annexin A11 in disease.

Ubiquitously expressed in many cell types, annexin A11 (Anxa11) is a member of the multigene family of Ca(2+)-regulated phospholipid-dependent and membrane-binding annexin proteins. Studies have shown that Anxa11 plays an important role in cell division, Ca(2+) signaling, vesicle trafficking and apoptosis. The deregulation and mutation of Anxa11 are involved in systemic autoimmune diseases, sarcoidosis and the development, chemoresistance and recurrence of cancers. Malfunction of Anxa11 may lead to or enhance the metastasis, invasion and drug resistance of cancers through the platelet-derived growth factor receptor (PDGFR) pathway and/or the mitogen-activated protein kinase (MAPK)/p53 pathway. In a variety of diseases, Anxa11 is most commonly reported to function through interactions with apoptosis-linked gene-2 protein (ALG-2) and/or calcyclin (S100A6). Although it has been little studied, Anxa11 is a promising biomarker for the diagnosis, treatment and prognosis of certain diseases. In this review, the associations of Anxa11 with Ca(2+)-regulated exocytosis, cytokinesis, sex differentiation, autoimmune diseases, thrombolysis and cancers are summarized and interpreted.

Metabolic fate of nicotinamide in higher plants.

Metabolism of [carbonyl-14C]nicotinamide was surveyed in various plant materials including the model plants, Arabidopsis thaliana, Oryza sativa and Lotus japonicus. In all plants studied, nicotinamide was used for the pyridine (nicotinamide adenine) nucleotide synthesis, probably after conversion to nicotinic acid. Radioactivity from [carbonyl-14C]nicotinamide was incorporated into trigonelline (1-N-methylnicotinic acid) and/or into nicotinic acid 1N-glucoside (Na-Glc). Trigonelline is formed mainly in leaves and cell cultures of O. sativa and L. japonicus and in seedlings of Trifolium incarnatum, Medicago sativa and Raphanus sativus. Trigonelline synthesis from nicotinamide is generally greater in leaves than in roots. Na-Glc was formed as the major nicotinic acid conjugate in A. thaliana and in tobacco Bright Yellow-2 cells. In seedlings of Chrysanthemum coronarium and Theobroma cacao, both trigonelline and Na-Glc were synthesized from [carbonyl-14C]nicotinamide. Trigonelline is accumulated in some seeds, mainly Leguminosae species. The pattern of formation of the nicotinic acid conjugates differs between species and organs.

Involvement of rapid nucleotide synthesis in recovery from phosphate starvation of Catharanthus roseus cells.

Growth of suspension-cultured Catharanthus roseus cells ceased during phosphate starvation, but the cells grew again upon addition of Pi even after long-term starvation. The metabolic fate of [(33)P]Pi was studied in 1-week-old stationary phase cells in ordinary culture and in 1- or 2-week-old Pi-starved cells. Immediately after administration, the most heavily labelled organic compounds are nucleotides, followed by sugar phosphates. Two weeks Pi starvation slowed down the speed of incorporation of (33)P into nucleotides. The RNA, protein, and free nucleotide content all decreased gradually during Pi starvation; however, these compounds, especially nucleotides, increased markedly in the 24 h after addition of Pi. These responses are found in all cells examined, although the total amounts of these compounds were lower in the long-term Pi-deficient cells. Of the nucleotides, a marked increase was observed in nucleoside triphosphates and UDP-glucose. The transcript level of phosphate transporter and the activities of acid phosphatase, 5'- and 3'-nucleotidase, and adenosine nucleosidase were all reduced by the addition of Pi. In contrast, the activities of adenine phosphoribosyltransferase, nicotinate phosphoribosyltransferase, and nicotinamidase, which are salvage enzymes of purine and pyridine nucleotides, were markedly increased in the Pi-fed cells. Little or no increase was observed in adenosine kinase. In the light of these results, the possible involvement of net nucleotide synthesis in the initial metabolic events of recovery from Pi deficiency are discussed.