Clinical efficacy of botulinum toxin type A in the treatment of fasciitis pain: A systematic review and meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to assess the effectiveness of botulinum toxin type A (BoNT-A) in reducing pain associated with fasciitis. By synthesizing the findings from multiple studies, we aimed to provide a comprehensive evaluation of the current evidence regarding the efficacy of BoNT-A in the treatment of fasciitis pain. METHODS: To identify studies for our report, we conducted electronic database searches of Embase, PubMed, Web of Science, and the Cochrane Library from their inception to November 20, 2022. We included only randomized controlled trials that examined the therapeutic effects of BoNT-A on fasciitis pain, with the primary outcome measure being the visual analog scale. We conducted statistical analyses using RevMan 5.4 software. RESULTS: Our final meta-analysis comprised 14 randomized controlled trials involving 537 participants, with 271 patients in the BoNT-A group and 266 patients in the control group. The overall effectiveness of BoNT-A in reducing fasciitis pain was significant, with a mean difference (MD) in visual analog scale score of -2.59 (95% confidence interval [CI], -3.36, -1.82); P < .00001; I2 = 88%. Subgroup analysis revealed that BoNT-A was particularly effective in treating plantar fasciitis (MD = -3.34 [95% CI, -4.08, -2.78]; P < .00001; I2 = 75%), lumbar back fasciitis (MD = -2.17 [95% CI, -3.82, -0.52]; P = .001; I2 = 93%), and neck and shoulder fasciitis (MD = -1.49 [95% CI, -2.76, -0.22]; P = .02; I2 = 61%). CONCLUSION: BoNT-A has a significant analgesic effect on fasciitis pain. Therefore, BoNT-A presents a promising alternative treatment option for fasciitis (PROSPERO 2022: CRD42022382805).

Relationship of Sulfatides Physiological Function and Peroxisome Proliferator-Activated Receptor α.

Sulfatides are unique sphingolipids present in the serum and the plasma membrane. Sulfatides exert important functions in a number of systems in the human body, including the nervous, immune, cardiovascular, and coagulation systems.Furthermore, it is closely related to tumor occurrence, development, and metastasis. Peroxisome proliferators-activated receptor α (PPARα) is a class of the nuclear receptor superfamily of transcription factors, which is a potential regulator of sulfatides. This review not only summarizes the current knowledge on the physiological functions of sulfatides in various systems, but also discusses the possible PPARα regulatory mechanisms in sulfatide metabolism and functions. The results of the present analysis provide deep insights and further novel ideas for expanding the research on the physiological function and clinical application of sulfatides.

Percutaneous Endoscopic Lumbar Discectomy for the Treatment of Recurrent Lumbar Disc Herniation: A Meta-analysis.

Objective: To evaluate the incidence and safety of clinical complications associated with percutaneous endoscopic lumbar discectomy (PELD) for the treatment of recurrent lumbar disc herniation (RLDH) by meta-analysis. Methods: PubMed, Embase, The Cochrane Library, and Web of Science electronic databases were searched for clinical studies on complications related to the treatment of RLDH with PELD. The search time extended from the databases' inception until May 2021. RevMan5.4 software was used for meta-analysis after two researchers independently scanned the literature, gathered data, and assessed the bias risk of the included studies. Results: A total of 8 clinical studies, including 1 randomized controlled trial and 7 cohort studies including 906 individuals, were included. According to the results of the meta-analysis, the overall complications (OR = 0.18, 95% CI: 0.04-0.83, p = 0.03) and dural tear rates (OR = 0.11, 95% CI: 0.01-0.92, p = 0.04) of PELD were lower than those of traditional fenestration nucleus pulposus removal. Moreover, the PELD group had a greater recurrence rate compared to the MIS-TLIF group (OR = 19.71, 95% CI: 3.68-105.62, p = 0.0005), and the difference was statistically significant. However, compared with MED and MIS-TLIF, there were no significant differences in the incidence of overall complications, dural tear, nerve root injury, and incomplete nucleus pulposus removal (P > 0.05). Conclusion: PELD is an effective and safe method for the treatment of recurrent lumbar disc herniation, with a lower incidence of complications and higher safety profile than traditional fenestration nucleus pulposus removal.

BMP2 as a promising anticancer approach: functions and molecular mechanisms.

Bone morphogenetic protein 2 (BMP2), a pluripotent factor, is a member of the transforming growth factor-beta (TGF-ß) superfamily and is implicated in embryonic development and postnatal homeostasis in tissues and organs. Experimental research in the contexts of physiology and pathology has indicated that BMP2 can induce macrophages to differentiate into osteoclasts and accelerate the osteolytic mechanism, aggravating cancer cell bone metastasis. Emerging studies have stressed the potent regulatory effect of BMP2 in cancer cell differentiation, proliferation, survival, and apoptosis. Complicated signaling networks involving multiple regulatory proteins imply the significant biological functions of BMP2 in cancer. In this review, we comprehensively summarized and discussed the current evidence related to the modulation of BMP2 in tumorigenesis and development, including evidence related to the roles and molecular mechanisms of BMP2 in regulating cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), cancer angiogenesis and the tumor microenvironment (TME). All these findings suggest that BMP2 may be an effective therapeutic target for cancer and a new marker for assessing treatment efficacy.

MicroRNA-138-1-3p sensitizes sorafenib to hepatocellular carcinoma by targeting PAK5 mediated ß-catenin/ABCB1 signaling pathway.

BACKGROUND: Sorafenib is a kinase inhibitor that is used as a first-line therapy in advanced hepatocellular carcinoma (HCC) patients. However, the existence of sorafenib resistance has limited its therapeutic effect. Through RNA sequencing, we demonstrated that miR-138-1-3p was downregulated in sorafenib resistant HCC cell lines. This study aimed to investigate the role of miR-138-1-3p in sorafenib resistance of HCC. METHODS: In this study, quantitative real-time PCR (qPCR) and Western Blot were utilized to detect the levels of PAK5 in sorafenib-resistant HCC cells and parental cells. The biological functions of miR-138-1-3p and PAK5 in sorafenib-resistant cells and their parental cells were explored by cell viability assays and flow cytometric analyses. The mechanisms for the involvement of PAK5 were examined via co-immunoprecipitation (co-IP), immunofluorescence, dual luciferase reporter assay and chromatin immunoprecipitation (ChIP). The effects of miR-138-1-3p and PAK5 on HCC sorafenib resistant characteristics were investigated by a xenotransplantation model. RESULTS: We detected significant down-regulation of miR-138-1-3p and up-regulation of PAK5 in sorafenib-resistance HCC cell lines. Mechanistic studies revealed that miR-138-1-3p reduced the protein expression of PAK5 by directly targeting the 3'-UTR of PAK5 mRNA. In addition, we verified that PAK5 enhanced the phosphorylation and nuclear translocation of ß-catenin that increased the transcriptional activity of a multidrug resistance protein ABCB1. CONCLUSIONS: PAK5 contributed to the sorafenib resistant characteristics of HCC via ß-catenin/ABCB1 signaling pathway. Our findings identified the correlation between miR-138-1-3p and PAK5 and the molecular mechanisms of PAK5-mediated sorafenib resistance in HCC, which provided a potential therapeutic target in advanced HCC patients.

Single-cell RNA sequencing reveals atlas of dairy goat testis cells.

Single-cell RNA sequencing (scRNA-seq) is useful for exploring cell heterogeneity. For large animals, however, little is known regarding spermatogonial stem cell (SSC) self-renewal regulation, especially in dairy goats. In this study, we described a high-resolution scRNA-seq atlas derived from a dairy goat. We identified six somatic cell and five spermatogenic cell subtypes. During spermatogenesis, genes with significantly changed expression were mainly enriched in the Notch, TGF-ß, and Hippo signaling pathways as well as the signaling pathway involved in the regulation of stem cell pluripotency. We detected and screened specific candidate marker genes ( TKTL1 and AES) for spermatogonia. Our study provides new insights into goat spermatogenesis and the development of testicular somatic cells.

Characterization of a transcription factor SlNAC7 gene from Suaeda liaotungensis and its role in stress tolerance.

NAC (NAM, ATAF1/2, CUC2) transcription factors play important roles in plant growth, development, and responses to abiotic stress. In this study, we cloned an NAC2 subfamily transcription factor gene (SlNAC7) from the halophyte Suaeda liaotungensis K., and conducted a series of studies to determine the characteristics and functions of this gene. The SlNAC7 coding region contains 1719 base pairs that encode a 573 amino acid long protein. SlNAC7 is expressed in the roots, stems, and leaves of S. liaotungensis, with the highest expression in the leaves. We found that SlNAC7 expression can be induced by drought, salt, cold, and abscisic acid. Transient expression in onion epidermal cells revealed that SlNAC7 is located in both the nucleus and cytoplasm. A transcriptional activation experiment in yeast showed that the transcriptional activation domain of SlNAC7 is located at the C terminus. When SlNAC7 was transformed into Arabidopsis under the control of a CaMV 35S promoter its overexpression was found to enhance the ability of transgenic plants to resist drought, salt, and cold stress. Moreover, these plants showed multiple changes in growth characteristics and physiological and biochemical indices in response to different stresses, as well as the upregulation of numerous stress-related genes. We have thus characterized a new halophyte-derived NAC transcription factor, SlNAC7, which can regulate plant growth and physiological and biochemical changes under adverse conditions by regulating the expression of stress-related genes, thereby enhancing plant stress resistance. SlNAC7 is a promising candidate for breeding new varieties of stress-tolerant crops.

PARP-1-regulated TNF-α expression in the dorsal root ganglia and spinal dorsal horn contributes to the pathogenesis of neuropathic pain in rats.

Emerging evidence has implicated poly-(ADP-ribose) polymerase 1 (PARP-1), a transcriptional coregulator, in a variety of inflammatory diseases. In the current study, the role of PARP-1 in neuropathic pain and the underlying mechanisms were investigated. Neuropathic pain was determined by assessing the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) following lumbar 5 spinal nerve ligation (SNL) in male rates. Western blotting, qRT-PCR, immunohistochemistry, chromatin immunoprecipitation (ChIP), and Co-IP assays were performed to elucidate the mechanisms. The results showed that SNL resulted in a significant increase in the expression and activation of PARP-1 in the ipsilateral L4/5 dorsal root ganglia (DRG) and spinal dorsal horn, which occurred on day one, reached peak on day 7, and persisted more than 2 weeks after surgery. Double immunofluorescence staining revealed that PARP-1 was expressed exclusively in DRG A-type and C-type neurons. In the spinal cord, PARP-1 mainly colocalized with the neuronal marker NeuN and the astrocytic marker GFAP specifically in the superficial lamina. Prior intrathecal (i.t.) injection of PJ-34, a PARPs inhibitor, or Tiq-A, a specific PARP-1 inhibitor, dose-dependently prevented the reductions in PWT and PWL following SNL. Established neuropathic pain-like hypersensitivity was also attenuated with i.t. injection of PJ-34 and Tiq-A starting on day 7 following SNL, a timepoint at which neuropathic pain was fully established. SNL-induced mechanical allodynia and thermal hyperalgesia were also alleviated by i.t. injection of PARP-1 siRNA following a reduction in PARP-1 expression in the dorsal horn. Moreover, the SNL-induced increases in TNF-α protein and mRNA in the dorsal horn and DRG were dramatically suppressed by i.t. injection of Tiq-A or PARP-1 siRNA. The i.t. lipopolysaccharide (LPS)-induced increase in the production of TNF-α in the dorsal horn was also inhibited by prior to i.t. injection of PARP-1 siRNA. Results of ChIP assay showed that SNL-induced PARP-1 activation promoted the binding of NF-κB p65 with the TNF-α promoter in the dorsal horn and that PARP-1 inhibition reduced this binding and suppressed TNF-α expression. Co-IP assay revealed that SNL caused a significant increase in the level of histone H1 poly(ADP)-ribosylation. Together, these results indicate that PARP-1-regulated TNF-α expression in the DRG and spinal dorsal horn following SNL contributes to the development and maintenance of neuropathic pain. Targeting PARP-1 might be a promising therapeutic strategy for the treatment of the chronic pain.

Baicalin Ameliorates Dexamethasone-Induced Osteoporosis by Regulation of the RANK/RANKL/OPG Signaling Pathway.

BACKGROUND: Osteoporosis is a chronic bone metabolism disorder affecting millions of the world population. The RANKL/RANK/OPG signaling pathway has been confirmed to be the main regulator of osteoporosis. It is of great interest to identify appropriate therapeutic agents that can regulate the RANKL/RANK/OPG pathway. Baicalin (BA) is a well-known traditional Chinese medicine formula against various inflammatory diseases with a proven role of the RANKL/RANK/OPG pathway regulation. However, the potential effect of BA on osteoporosis and the mechanisms underlying this remain unclear. In the present study, we aimed to evaluate the efficacy of BA in the prevention of dexamethasone (DEX)-induced osteoporosis in zebrafish. METHODS: In this study, growth and development changes of zebrafish and calcein staining were assessed with a micrograph. The expression levels of RANKL and OPG and transcription factors in response to DEX induction and BA administration were evaluated by Western blotting and qRT-PCR. In addition, the intermolecular interactions of BA and RANKL were investigated by molecular docking. RESULTS: Results show that BA enhances the growth and development of dexamethasone (DEX)-induced osteoporosis in zebrafish larvae. Calcein staining and calcium and phosphorus determination revealed that BA ameliorates mineralization of DEX-induced osteoporosis zebrafish larvae. BA also regulates the expression of RANKL and OPG and hampers the changes in gene expression related to bone formation and resorption under the induction of DEX in zebrafish. It can be inferred by molecular docking that BA may interact directly with the extracellular domain of RANKL. CONCLUSION: The findings, herein, reveal that BA ameliorates DEX-induced osteoporosis by regulation of the RANK/RANKL/OPG signaling pathway.

PAK6: a potential anti-cancer target

p21-activated kinase 6 (PAK6) is a member of the PAK family of serine/threonine kinases that are known effectors of Rho GTPases Cdc42 and Rac. PAKs regulate a large number of complex cellular mechanisms, including cell motility, morphology, and tumor development. PAK6, initially cloned as an interacting partner of the androgen receptor (AR), is associated with an array of cellular processes implicated in tumor progression. However, the full biological implications of PAK6 activity during cancer remain poorly understood. In this review, we assess our current understanding of the physiological roles of classical PAK6 functionality in mammals, in addition to its emerging role in tumorigenesis.

Friend or foe, the role of EGR-1 in cancer.

Early growth response-1 (EGR-1), also termed NEFI-A and Krox-24, as a multi-domain protein is implicated in several vital physiological processes, including development, metabolism, cell growth and proliferation. Previous studies have implied that EGR-1 was producing in response to the tissue injury, immune response and fibrosis. Meanwhile, emerging studies stressed the pronounced correlation of EGR-1 and human cancers. Nevertheless, the intricate mechanisms of cancer-reduce EGR-1 alteration still poorly characterized. In the review, we evaluated the effects of EGR-1 in tumor cell proliferation, apoptosis, migration, invasion and tumor microenvironment, and then, we dwell on the intricate signaling pathways that EGR-1 involved in. The aberrantly expressed of EGR-1 in cancers are expected to provide a new cancer therapy strategy or a new marker for assessing treatment efficacy.

Upregulation of matrix metalloproteinase-9/2 in the wounded tissue, dorsal root ganglia, and spinal cord is involved in the development of postoperative pain.

Emerging evidence implicates the upregulation of matrix metalloproteinase (MMP)-9/2 in the dorsal root ganglion (DRG) and spinal cord as a contributor to the pathogenesis of chronic pain. In the current study, the expression of MMP-9/2 in wounded tissue, ipsilateral DRG, and the spinal dorsal horn as well as its role in the development of postoperative pain were examined following plantar incision in rats. Our results showed that plantar incision resulted in increased expression of MMP-9/2 in wounded tissue and ipsilateral L4/5 DRGs. Although gelatin zymography detected an increased activity of MMP-9, only MMP-2 protein was increased in the spinal cord. Results of double immunofluorescence staining showed MMP-2 expression in DRG neurons and satellite glial cells, but MMP-9 was found only in neurons. In the spinal cord, MMP-2 was expressed in neurons and astrocytes, and MMP-9 was expressed in neurons and somewhat in microglial cells. Planter incision also elicited increased expression of p-Erk, p-p38, and IL-1ß in wounded tissue, ipsilateral L4/5 DRGs, and dorsal horn. Prior intraplantar or intrathecal injection of MMP-9- and MMP-2-specific inhibitors partially prevented reductions of paw withdrawal threshold and paw withdrawal latency following plantar incision. The maturation of IL-1ß was also inhibited by the treatment. Moreover, MMP-9 inhibition suppressed p38, and MMP-2 inhibitor reduced the Erk phosphorylation in wounded tissue, DRGs, and dorsal horn. Immunofluorescence staining detected colocalization of MMP-9 with p38 and MMP-2 with Erk in DRG and spinal cord. Together, the above results reveal that upregulated MMP-9 via p38/IL-1ß and MMP-2 via Erk/IL-1ß signaling in the wounded tissue, ipsilateral DRG, and dorsal horn contribute to the development of postoperative pain.

PAK5 promotes the migration and invasion of cervical cancer cells by phosphorylating SATB1.

p21-activated kinase 5 (PAK5) is involved in several oncogenic signaling pathways and its amplification or overexpression has been found in various types of cancer; however, the pathophysiologic role of PAK5 in cervical cancer (CC) remains elusive. This study aims to elucidate the effects of PAK5 on CC metastasis and its specific regulation mechanism. We performed western blotting and immunohistochemistry (IHC) analysis and found that the expression levels of PAK5 were significantly upregulated in CC cells and tissues. In addition, statistical analysis via IHC showed that increased PAK5 significantly correlated with CC progression. Mn2+-Phos-tag SDS-PAGE, western blotting, immunofluorescence and dual luciferase reporter assays were utilized to determine the involvement of SATB1 in PAK5-mediated epithelial-mesenchymal transition (EMT). We found that PAK5-mediated special AT-rich binding protein-1 (SATB1) phosphorylation on Ser47 initiated EMT cascade and promoted migration and invasion of CC cells. Furthermore, overexpression of PAK5 induced lung metastasis of CC cells in xenograft modes. Taken together, we conclude that PAK5 is a novel prognostic indicator and plays an important role in the CC metastasis.

Spectroscopic characterization of DOM and the nitrogen removal mechanism during wastewater reclamation plant.

The performance of the Sha-he wastewater reclamation plant was evaluated in this study. To remove residual nitrogen after Anaerobic-Anoxic-Oxic (A2O) treatment, three multistage Anoxic-Oxic (A/O) were added to investigate the nitrogen removal efficiency and its mechanism. In addition, the constituents and evolution of dissolved organic matter (DOM) during wastewater reclamation was also investigated using a method combining fluorescence spectroscopy with fluorescence regional integration (FRI). The results suggested that multistage A/O treatment can effectively improve the nitrogen removal ability under low concentrations of carbon sources. The total nitrogen (TN) exhibits significantly positive correlation with fulvic acid-like materials and humic acid-like materials. The correlation coefficient for TN and fulvic acid-like substances (R2 = 0.810, P < 0.01) removal was greater than that of humic acid-like substances (R2 = 0.636, P < 0.05). The results indicate that nitrogen removal may be achieved with the fulvic-like and humic-like substances, and the removal effects were higher by fulvic acid-like substances than humic-like substances, mostly due to that the latter were relatively more difficult to be utilized as carbon source during the nitrogen removal process. The effluent water quality of biological treatment reached the first grade A standard of "Cities sewage treatment plant pollutant discharge standard" (GB18918-2002). In addition, the effluent from the membrane bioreactor reached the "Standards of reclaimed water quality" (SL368-2006).

Co4N Nanowires: Noble-Metal-Free Peroxidase Mimetic with Excellent Salt- and Temperature-Resistant Abilities.

Compared to natural enzymes, nanomaterial-based artificial enzymes have attracted immense attention because of their high stability and cost-effectiveness. In this study, cobalt nitride (Co4N) as a noble-metal-free artificial enzyme exhibiting highly intrinsic peroxidase-like activity and good stability was reported. Kinetic studies revealed that the resultant Co4N nanowires (NWs) exhibited a stronger affinity for 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 than HRP. Compared to Co3O4 NWs, Co4N NWs exhibited highly improved catalytic activities, with H2O2 exhibiting an apparent Km approximately 2 orders of magnitude less than that of Co3O4. In particular, the peroxidase-like activity of Co4N was maintained well over a wide range of temperatures and ionic strength. A Co4N-based method was further developed for the detection of glucose with good sensitivity and reliability. Because of advantages such as easy storage, cost-effectiveness, high sensitivity, and outstanding stability, Co4N NWs demonstrate the potential for replacing noble-metal-based peroxidase mimetics in a wide range of promising applications.

Changes in the Intestinal Microbiota of Gibel Carp (Carassius gibelio) Associated with Cyprinid herpesvirus 2 (CyHV-2) Infection.

Gut microbiota are integral to the host, and have received increased attention in recent years. However, information regarding the intestinal microbiota of many aquaculture animals is insufficient; elucidating the dynamics of the intestinal microbiota can be beneficial for nutrition, immunity, and disease control. In this study, we used 16S rRNA sequencing to observe changes in the intestinal microbiota of gibel carp (Carassius auratus gibelio) associated with cyprinid herpesvirus 2 (CyHV-2) infection. Our results indicate that the diversity of the intestinal microbiota was strongly reduced, and the composition was dramatically altered following CyHV-2 infection. The most dominant species in healthy fish were Cetobacterium, Rhodobacter, and Crenothrix; meanwhile, Cetobacterium, Plesiomonas, Bacteroides, and Flavobacterium were the most abundant species in sick fish. Plesiomonas was highly abundant in infected samples, and could be used as a microbial biomarker for CyHV-2 infection. Chemical properties of the aquaculture water were significantly correlated with the microbial community structure; however, it is difficult to determine whether these changes are a cause or consequence of infection. However, it may be possible to use probiotics or prebiotics to restore the richness of the host intestinal microbiota in infected animals to maintain host health.