Deciphering resveratrol's role in modulating pathological pain: From molecular mechanisms to clinical relevance.

Pathological pain, a multifaceted and debilitating ailment originating from injury or post-injury inflammation of the somatosensory system, poses a global health challenge. Despite its ubiquity, reliable therapeutic strategies remain elusive. To solve this problem, resveratrol, a naturally occurring nonflavonoid polyphenol, has emerged as a potential beacon of hope owing to its anti-inflammatory, antioxidant, and immunomodulatory capabilities. These properties potentially position resveratrol as an efficacious candidate for the management of pathological pain. This concise review summaries current experimental and clinical findings to underscore the therapeutic potential of resveratrol in pathological pain, casting light on the complex underlying pathophysiology. Our exploration suggests that resveratrol may exert its analgesic effect by the modulating pivotal signaling pathways, including PI3K/Akt/mTOR, TNFR1/NF-κB, MAPKs, and Nrf2. Moreover, resveratrol appears to attenuate spinal microglia activation, regulate primary receptors in dorsal root sensory neurons, inhibit pertinent voltage-gated ion channels, and curb the expression of inflammatory mediators and oxidative stress responses. The objective of this review is to encapsulate the pharmacological activity of resveratrol, including its probable signaling pathways, pharmacokinetics, and toxicology pertinent to the treatment of pathological pain. Hopefully, we aim to map out promising trajectories for the development of resveratrol as a potential analgesic.

Bidirectional fermentation of Monascus and Mulberry leaves enhances GABA and pigment contents: establishment of strategy, studies of bioactivity and mechanistic.

Bidirectional fermentation is a technology that utilizes fungi to ferment medicinal edible substrates, with synergistic and complementary advantages. In this work, a fermentation strategy was established to produce a high yield of γ-aminobutyric acid (GABA) and Monascus pigments (MPs) using Monascus and mulberry leaves (MLs). Firstly, the basic fermentation parameters were determined using single-factor experiments, followed by Plackett-Burman (PB) experimental design to identify MLs, glucose, peptone, and temperature as significant influencing factors. The fermentation parameters were optimized using an artificial neural network (ANN). Finally, the effects of bidirectional fermentation of MLs and Monascus were investigated by bioactivity analysis, microstructure observation, and RT-qPCR. The outcomes showed that the bidirectional fermentation significantly increased the bioactive content and promoted the secondary metabolism of Monascus. The established fermentation conditions were 44.2 g/L of MLs, 57 g/L of glucose, 15 g/L of peptone, 1 g/L of MgSO4, 2 g/L of KH2PO4, 8% (v/v) of inoculum, 180 rpm, initial pH 6, 32 °C and 8 days. The content of GABA reached 13.95 g/L and the color value of MPs reached 408.07 U/mL. This study demonstrated the feasibility of bidirectional fermentation of MLs and Monascus, providing a new idea for the application of MLs and Monascus.

Causal association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma: a two-sample Mendelian randomization study.

Background: Despite numerous observational studies on the association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma, causal inferences remain ambiguous due to confounding and reverse causality. This study aimed to elucidate the causal relationship between serum 25-Hydroxyvitamin D levels and melanoma incidence using Mendelian randomization (MR). Methods: A two-sample MR was conducted using genetic variants associated with serum 25-Hydroxyvitamin D levels as instrumental variables. Summary statistics for these variants were derived from genome-wide association studies, and those for melanoma risk were obtained from a comprehensive melanoma case-control study. Robustness of the results was assessed through sensitivity analyses, including the "leave-one-out" approach and tests for potential pleiotropy. Results: The MR analysis provided substantial evidence of a positive causal relationship between serum 25-Hydroxyvitamin D levels and the incidence of cutaneous melanoma, suggesting that each unit increase in serum 25-Hydroxyvitamin D levels corresponds with an increased risk of melanoma. Tests for pleiotropy showed minimal effects, and the sensitivity analysis confirmed no disproportionate influence by any individual single nucleotide polymorphism (SNP). Conclusion: The findings indicated a potentially causal positive association between serum 25-Hydroxyvitamin D levels and melanoma risk, challenging traditional beliefs about vitamin D's role in melanoma. This emphasizes the need for a balanced and personalized approach to vitamin D supplementation and sun exposure, particularly in high-risk populations. These results should be interpreted with caution due to potential unrecognized pleiotropy and confounding factors. Future research should focus on validating these findings in diverse populations and exploring underlying biological mechanisms.

Glutathione and selenium nanoparticles have a synergistic protective effect during cryopreservation of bull semen.

Introduction: In the present study, the synergistic protective effect of co-supplementation of glutathione (GSH) with selenium nanoparticles (SeNPs) on the cryopreservation efficiency of bull semen was analyzed. Methods: After collection, the ejaculates of Holstein bulls were subsequently diluted with a Tris extender buffer supplemented with different concentrations of SeNPs (0, 1, 2, and 4 µg/ml), followed by semen equilibration at 4°C and assessment of sperm viability and motility. Subsequently, the ejaculates of Holstein bulls were pooled, split into four equal groups, and diluted with a Tris extender buffer supplemented with basic extender (negative control group, NC group), 2 µg/ml SeNPs (SeNPs group), 4 mM GSH (GSH group), and 4 mM GSH plus 2 µg/ml SeNPs (GSH + SeNPs group). After cryopreservation, motility, viability, mitochondrial activity, plasma membrane integrity, acrosome integrity, concentration of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT), and ability of frozen-thawed sperm cells to support in vitro embryonic development were evaluated. Results and discussion: No side effect of SeNPs concentrations applied in the current study on the motility and viability of equilibrated bull spermatozoa was found. Meanwhile, supplementation of SeNPs significantly promoted the motility and viability of equilibrated bull spermatozoa. Furthermore, the co-supplementation of GSH with SeNPs effectively protected bull spermatozoa from cryoinjury as expressed by promoting semen motility, viability, mitochondrial activity, plasma membrane integrity, and acrosome integrity. Finally, the enhanced antioxidant capacity and embryonic development potential in the frozen-thawed bull spermatozoa cryopreserved by co-supplementation of GSH with SeNPs further confirmed the synergistic protective effect of co-supplementation of GSH with SeNPs on the cryopreservation of bull semen.

Effects of dietary oat supplementation on carcass traits, muscle metabolites, amino acid profiles, and its association with meat quality of Small-tail Han sheep.

Oat supplementation of the ruminant diet can improve growth performance and meat quality traits, but the role of muscle metabolites has not been evaluated. This study aimed to establish whether oat grass supplementation (OS) of Small-tail Han sheep improved growth performance and muscle tissue metabolites that are associated with better meat quality and flavor. After 90-day, OS fed sheep had higher live-weight and carcass-weight, and lower carcass fat. Muscle metabolomics analysis showed that OS fed sheep had higher levels of taurine, l-carnitine, inosine-5'-monophospgate, cholic acid, and taurocholic acid, which are primarily involved in taurine and hypotaurine metabolism, purine metabolism, and bile acid biosynthesis and secretion, decreased fat accumulation and they promote functional or flavor metabolites. OS also increased muscle levels of amino acids that are attributed to better quality and flavorsome mutton. These findings provided further evidence for supplementing sheep with oat grass to improve growth performance and meat quality.

Glutathione ameliorates the meiotic defects of copper exposed ovine oocytes via inhibiting the mitochondrial dysfunctions.

Regardless of the essential role of copper (Cu) in the physiological regulation process of mammalian reproduction, excessive exposure to Cu triggers the meiotic defects of porcine oocytes via compromising the mitochondrial functions. However, the connections between the excessive Cu exposure and meiotic defects of ovine oocytes have not been reported. In this study, the effect of copper sulfate (CuSO4) exposure on the meiotic potentials of ovine oocytes was analyzed. Subsequently, the ameliorative effect of glutathione (GSH) supplementation on the meiotic defects of CuSO4 exposed ovine oocytes was investigated. For these purposes, the in vitro maturation (IVM) of ovine cumulus oocyte complexes (COCs) was conducted in the presence of 5, 10, 20 and 40 µg/mL of CuSO4 supplementation. Subsequently, different concentrations of GSH (2, 4 and 8 mM) were added to the IVM medium containing CuSO4 solution. After IVM, the assay, including nuclear maturation, spindle organization, chromosome alignment, cytoskeleton assembly, cortical granule (CGs) dynamics, mitochondrial function, reactive oxygen species (ROS) generation, apoptosis, epigenetic modification and fertilization capacity of ovine oocytes were performed. The results showed that excessive Cu exposure triggered the meiotic defects of ovine oocytes via promoting the mitochondrial dysfunction related oxidative stress damage. Moreover, the GSH supplementation, not only ameliorated the decreased maturation potential and fertilization defect of CuSO4 exposed oocytes, but inhibited the mitochondrial dysfunction related oxidative stress damage, ROS generation, apoptosis and altered H3K27me3 expression in the CuSO4 exposed oocytes. Combined with the gene expression pattern, the finding in the present study provided fundamental bases for the ameliorative effect of GSH supplementation on the meiotic defects of CuSO4 exposed oocytes via inhibiting the mitochondrial dysfunctions, further benefiting these potential applications of GSH supplementation in the mammalian IVM system and livestock breeding suffering from the excessive Cu exposure.

Characteristics of microbiota, core sulfate-reducing taxa and corrosion rates in production water from five petroleum reservoirs in China.

Microbial diversity and activities in petroleum reservoir systems can be altered by water-flooding operation, but the current understanding of the mechanism for such changes in microbial composition characteristics and community is inadequate. In this study, microbial communities especially functional groups in production water from five petroleum reservoirs in China were investigated by chemical and molecular biological analyses. The dominant and core phyla in the five oil reservoirs were Proteobacteria, Deferribacterota, Firmicutes, Desulfobacterota, Euryarchaeota and Thermoplasmatota. At the genus level, the dominant taxa in each petroleum reservoir were different, and not all of the dominant genera were the core members across the five oil reservoirs. The microbiologically influenced corrosion (MIC) were investigated for the functional groups in each production water. The corrosion rates in production water were higher than controls with a positive correlation to the abundances of sulfate-reducing prokaryotes (SRP). The SRP diversity based on the aprA and dsrA gene analysis showed that obvious differences were evident between onshore (JS, SL, DQ and XJ) and offshore (BS) oilfields. The core SRP taxa in onshore oilfields were Desulfomicrobium and Desulfovibrio, also with Desulfotomaculum in medium/low-temperature oil reservoirs (DQ and XJ), but in high-temperature petroleum reservoirs (JS, BS and SL), Archaeoglobus, Thermodesulfobacterium and Thermodesulfovibrio were the core groups. Statistical analysis indicated that temperature, electron acceptors and donors showed significant influence on the SRP community. This research reveals the characteristics of microbial and functional community as well as their interaction mechanism on corrosion in petroleum reservoir environments, and will improve industrial bio-control and management of MIC in oilfields.

A novel biflavone from Reineckia carnea induces apoptosis of human renal cancer 786-O cells.

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system, which is highly invasive, metastatic, and insensitive to radiotherapy and chemotherapy. Chinese herbal medicine has always been an important source of anti-tumor drug development. Reineckia carnea Kunth is a traditional herb commonly used by the Miao nationality in southwest China. In this study, the extract of Reineckia carnea was isolated and purified by reverse phase preparative chromatography and other chromatographic techniques. According to the physicochemical properties and spectral data, the structure of the compound was identified, and a novel biflavone compound named Reineckia-biflavone A (RFA) was obtained. The result of antiproliferative activity showed that RFA had cytotoxicity on 786-O cells with an IC50 value of 19.34 µmol/L. The results of CCK-8 and hemolysis assays showed that RFA was not significantly cytotoxic to both red blood cells (RBC) and peripheral blood mononuclear cells (PBMC). By Hoechst 33258 apoptosis staining, typical apoptotic morphology was observed under fluorescence microscope. RFA could induce the apoptosis of 786-O cells with the increase of apoptosis rate. The cell cycle tests showed that the cell proportion was obviously arrested in the S phase. At the same time, RFA could decrease the mitochondrial membrane potential and increase the intracellular free Ca2+ concentration. Western blot showed that the expression levels of pro-apoptotic proteins (Bax, Caspase-3, Cleaved Caspase-3, and Cytochrome c) in cells rose, while the expression level of anti-apoptotic proteins (Bcl-2) declined significantly. In conclusion, this study suggests that the RFA is a new biflavone determined by SciFinder retrieval. The apoptosis may be triggered by RFA through the mitochondrial pathway, which is mediated by up-regulating the intracellular calcium ion, down-regulating the mitochondrial membrane potential, and changing the apoptosis-related proteins.

[Kinesio Taping combined with electroacupuncture for the treatment of Bigliani typeâ subacromial impingement syndrome].

OBJECTIVE: To investigate the clinical effect of Kinesio Taping combined with electroacupuncture in the treatment of Bigliani typeⅠsubacromial impingement syndrome. METHODS: From January 2019 to June 2021, 82 cases with Bigliani typeⅠsubacromial impingement syndrome were selected and divided into treatment group and control group. Treatment group included 41 cases, 23 males and 18 females, aged from 20 to 52 years old, with an average of (39.31±5.80)years old. There were 12 cases on left shoulder and 29 cases on right shoulder. The course of disease was from 3.2 to 35.4 months. The treatment group was treated with Kinesio Taping and electroacupuncture. In control group, there were 41 cases, including 22 males and 19 females, aged from 19 to 53 years old with an average of (40.67±6.13) years old, 30 cases on right shoulder, 11 cases on left shoulder. The courses of disease was from 3.0 to 36.0 months. The control group was treated with simple shoulder electroacupuncture. Patients in both groups were treated with electroacupuncture 3 times a week for 3 weeks. After each electroacupuncture treatment in the treatment group, the Kinesio Taping was applied immediately and kept for 2 days. Before treatment, immediately after treatment, and after 1, 3, 8 weeks, the shoulder joint Constant-Murley score, pain visual analogue scale (VAS), and shoulder joint range of motion were used to evaluate the treatment effect. RESULTS: After 1 week of treatment, there was 1 patient in treatment group refused treatment due to hypersensitivity to Kinesio Taping, 1 patient in control group was allergic to the metal needle and refused treatment. And the other 80 patients completed all treatment. Immediately after treatment, and 1, 3, and 8 weeks after treatment, VAS of treatment group were (2.06±1.03), (2.74±1.66), (3.28±1.04), and (3.90±0.12) points, respectively. The Constant-Murley scores of shoulder joint were(86.41±3.52), (82.44±3.14), (80.46±2.54), (76.97±2.01) points. VAS of control group were(3.35±0.41), (3.08±0.92), (3.77±0.67), (3.96±1.04) points, and the Constant-Murley scores of the shoulder joint were(75.82±2.73), (74.72±1.53), (73.66±1.53), (70.68±1.95) points respectively. Immediately after treatment, VAS, Constant-Murley score, and shoulder range of motion between two groups were better than those of before treatment (P<0.05), and the difference was statistically significant between two groups after treatment (P<0.05). One week after treatment, VAS, Constant-Murley score, and shoulder joint range of motion between two groups were better than those of before treatment (P<0.05), but there was no significant difference in VAS between two groups (P>0.05). There were significant differences in the Constant-Murley score and shoulder range of motion between two groups (P<0.05). At 3 and 8 weeks after treatment, VAS, Constant-Murley score, and the range of motion of shoulder joints between two groups were better than those of before treatment (P<0.05), but there was no significant difference between two groups(P>0.05). CONCLUSION: The treatment for bigliani typeⅠsubacromial impingement syndrome with Kinesio Taping combined with electroacupuncture can reduce pain, effectively improve the function of shoulder joint. In addition, with Kinesio Taping protection when motion, the patients sports ability can be improved obviously, with good immediate effect, and no trauma. If the patients are willing to accept it, it would be an immediate and effective treatment.

Robust route to H2O2 and H2 via intermediate water splitting enabled by capitalizing on minimum vanadium-doped piezocatalysts.

H2O2 is an environmentally friendly chemical for a wide range of water treatments. The industrial production of H2O2 is an anthraquinone oxidation process, which, however, consumes extensive energy and produces pollution. Here we report a green and sustainable piezocatalytic intermediate water splitting process to simultaneously obtain H2O2 and H2 using single crystal vanadium (V)-doped NaNbO3 (V-NaNbO3) nanocubes as catalysts. The introduction of V improves the specific surface area and active sites of NaNbO3. Notably, V-NaNbO3 piezocatalysts of 10 mg exhibit 3.1-fold higher piezocatalytic efficiency than the same catalysts of 50 mg, as more piezocatalysts lead to higher probability of aggregation. The aggregation causes reducing active sites and decreased built-in electric field due to the neutralization between different nano-catalysts. Remarkably, piezocatalytic H2O2 and H2 production rates of V-NaNbO3 (10 mol%) nanocubes (102.6 and 346.2 µmol·g-1·h-1, respectively) are increased by 2.2 and 4.6 times compared to the as-prepared pristine NaNbO3 counterparts, respectively. This improved catalytic efficiency is attributed to the promoted piezo-response and more active sites of NaNbO3 catalysts after V doping, as uncovered by piezo-response force microscopy (PFM) and density functional theory (DFT) simulation. More importantly, our DFT results illustrate that inducing V could reduce the dynamic barrier of water dissociation over NaNbO3, thus enhancing the yield of H2O2 and H2. This facile yet robust piezocatalytic route using minimal amounts of catalysts to obtain H2O2 and H2 may stand out as a promising candidate for environmental applications and water splitting. Electronic Supplementary Material: Supplementary material (typical Raman spectra of NaNbO3 and V-NaNbO3 with various doping concentrations (Fig. S1). XPS spectra of Na 1s (Fig. S2). PL spectra of solution obtained from the piezocatalytic system using NaNbO3 and V-NaNbO3 (10 mol%) as the catalysts after 1 h (Fig. S3). The length of NaNbO3 and V-NaNbO3 nanocubes calculated from XRD data of their (101) planes (Table S1)) is available in the online version of this article at 10.1007/s12274-022-4506-0.

Beneficial Effect of Selenium Doped Carbon Quantum Dots Supplementation on the in vitro Development Competence of Ovine Oocytes.

Background: After the synthesis of selenium doped carbon quantum dots (Se/CDs) via a step-by-step hydrothermal synthesis method with diphenyl diselenide (DPDSe) as precursor, the beneficial effects of Se/CDs' supplementation on the in vitro development competence of ovine oocytes were firstly investigated in this study by the assay of maturation rate, cortical granules' (CGs) dynamics, mitochondrial activity, reactive oxygen species (ROS) production, epigenetic modification, transcript profile, and embryonic development competence. Results: The results showed that the Se/CDs' supplementation during the in vitro maturation (IVM) process not only enhanced the maturation rate, CGs' dynamics, mitochondrial activity and embryonic developmental competence of ovine oocytes, but remarkably decreased the ROS production level of ovine oocytes. In addition, the expression levels of H3K9me3 and H3K27me3 in the ovine oocytes were significantly up-regulated after the Se/CDs' supplementation, in consistent with the expression levels of 5mC and 5hmC. Moreover, 2994 up-regulated differentially expressed genes (DEGs) and 846 repressed DEGs were found in the oocytes after the Se/CDs' supplementation. According to the analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), these DEGs induced by the Se/CDs' supplementation were positively related to the progesterone mediated oocyte maturation and mitochondrial functions. And these remarkably up-regulated expression levels of DEGs related to oocyte maturation, mitochondrial function, and epigenetic modification induced by the Se/CDs' supplementation further confirmed the beneficial effect of Se/CDs' supplementation on the in vitro development competence of ovine oocytes. Conclusion: The Se/CDs prepared in our study significantly promoted the in vitro development competence of ovine oocytes, benefiting the extended research about the potential applications of Se/CDs in mammalian breeding technologies.

Phlorizin alleviates cholinergic memory impairment and regulates gut microbiota in d-galactose induced mice.

We explored the effect of phlorizin against cholinergic memory impairment and dysbacteriosis in D-galactose induced ICR mice. The control (CON) group, D-galactose model (DGM) group, and three groups (DG-PL, DG-PM, DG-PH) treated with phlorizin at 0.01%, 0.02%, and 0.04% (w/w) in diets were raised for 12 weeks. Supplementing with phlorizin reversed the loss of organ coefficient and body weight caused by D-galactose. The functional abilities of phlorizin on hippocampal-dependent spatial learning and memory, anti-oxidation, anti-inflammation were also observed. Meanwhile, phlorizin intervention upregulated the gene expression of Nrf2, GSH-PX, SOD1, decreased the gene expression of NF-κB, TLR-4, TNF-α, and IL-1ß in the hippocampus, while enhanced the gene expression of JAM-A, Mucin2, Occludin in the caecum. Furthermore, a neurotransmitter of acetylcholine (ACh) was enhanced, while acetylcholinesterase (AChE) activity was inhibited by phlorizin administration. Moreover, phlorizin administration increased short-chain fatty acids (SCFAs) content, and reduced lipopolysaccharides (LPS) levels, which may relate to the rebuilding of gut microbiota homeostasis. Treatment with phlorizin may be an effective intervention for alleviating cognitive decline and gut microbiota dysbiosis.

Genome-Wide Characterization and Expression Analysis of GATA Transcription Factors in Response to Methyl Jasmonate in Salvia miltiorrhiza.

Salvia miltiorrhiza is an important medicinal plant, which is mainly used for treatment of cardiovascular and cerebrovascular diseases. GATA transcription factors are evolutionarily conser-ved proteins that play essential roles in biological process of plants. In this study, we systematically characterized the GATA transcription factors in S. miltiorrhiza. A total 28 SmGATA genes were identified and divided into four subfamilies based on phylogenetic analysis and domain. SmGATA genes being clustered into a subfamily have similar conserved motifs and exon-intron patterns, and unevenly distribute on eight chromosomes of S. miltiorrhiza. Tissue-specific expression analysis based on transcriptome datasets showed that the majority of SmGATA genes were preferentially expressed in roots. Under methyl jasmonate (MeJA) treatment, the quantitative real-time PCR (qRT-PCR) analysis indicated that several SmGATA genes in roots showed distinct upregulation post-MeJA treatment, especially SmGATA08, which was highly responsive to MeJA, and might be involved in the jasmonate signal, thereby affecting root growth, development, tolerance to various stresses, or secondary metabolites biosynthesis. The study found that several SmGATAs, like SmGATA08, are highly responsive to MeJA, indicating that these SmGATAs might be vital in the biosynthesis of tanshinones and phenolic acids by regulating the response to MeJA in S. miltiorrhiza. Our results laid the foundation for understanding their biological roles and quality improvement in S. miltiorrhiza.

Computed tomography-guided iodine-125 radioactive seed implantation in small-cell lung cancer: A retrospective study.

Purpose: To explore the efficacy of computed tomography (CT)-guided iodine-125 (125I) radioactive seed implantation for the treatment of small-cell lung cancer (SCLC). Material and methods: A total of 12 SCLC patients were retrospectively enrolled. All patients underwent CT-guided 125I seed implantation therapy, and were followed up until death, the last visit time, or study end time. Primary endpoint was the overall response rate (ORR). Secondary endpoints were local control rate (LCR), progression-free survival (PFS), overall survival (OS), and safety. Results: All patients were successfully implanted with 125I radioactive seeds. The ORR at 2, 6, 12, and 24 months after implantation was 83.3%, 63.6%, 50%, and 40%, respectively; the LCR at 1 and 2 years were 75% (6/8) and 60% (3/5), respectively; the median PFS and OS were 8 and 12 months, respectively; and the OS rate at 6, 12, and 24 months after implantation was 91.67%, 66.67%, and 41.67%, respectively. No surgery-related deaths occurred. During the follow-up period, mild complications were observed in patients, including worsening cough, hemoptysis, and pneumothorax. Conclusions: CT-guided 125I seed implantation therapy is a safe and effective supplementary treatment for SCLC patients, who cannot tolerate radiotherapy.

Inhibition of Nuclear Factor Kappa B as a Therapeutic Target for Lung Cancer.

CONTEXT: A wide variety of malignancies common to humans display abnormal constitutive expression of nuclear factor kappa beta (NF-κß). The study of NF-κß can increase understanding of its role in cancer, especially in lung-tumor formation. OBJECTIVE: This review intended to examine the research on the impact of the NF-κß signaling pathway on the development of malignancies of the lungs and the advances in the regulation of that pathway to mitigate and provide treatment for lung carcinoma. DESIGN: The research team performed a narrative review by searching the PubMed, EMBASE, and Web of Science databases. The search used the keywords NF-κB or NF-kappa B or nuclear factor kappa B and non-small-cell lung cancer or non-small-cell lung carcinoma or NSCLC or lung cancer or lung adenocarcinoma or lung squamous carcinoma. SETTING: This study were conducted at Department of Respiratory and Critical Care Medicine, Qingxian People's Hospital, Cangzhou City, Hebei Province, People's Republic of China. RESULTS: As a major cell survival signal, nuclear factor-kappaB (NF-kappaB) is involved in multiple steps in carcinogenesis and in cancer cell's resistance to chemo- and radio-therapy. Recent studies with animal models and cell culture systems have established the links between NF-kappaB and lung carcinogenesis, highlighting the significance of targeting NF-kappa signaling pathway for lung cancer treatment and chemoprevention. CONCLUSIONS: While no convincing evidence exists that survival of lung cancer cells is dependent on NF-κß, inhibition of NF-κß is a potent supporting therapy for enhancing the therapeutic effects of chemotherapy and radiotherapy. Constitutive and therapeutically induced activation of NF-κß reduces the tumor-massacre effect of treatment, so inhibiting NF-κß might increase antitumor activity.

Acupuncture around the greater tuberosity of the femur combined with acupuncture at Xuehai acupoint alleviates the postoperative pain of elderly patients with intertrochanteric fracture.

OBJECTIVE: To determine the efficacy of acupuncture around the greater tuberosity of the femur (AGTF) combined with acupuncture at Xuehai acupoint for postoperative pain in elderly patients with intertrochanteric fracture. METHODS: A total of 97 elderly patients with intertrochanteric fracture treated by proximal femoral nail antirotation (PFNA) were enrolled and randomly assigned into an observation group (Obs group, n=48) and a control group (Con group, n=49). The Obs group was treated by aspirin and AGTF combined with acupuncture at Xuehai acupoint for analgesia, while the Con group was treated by aspirin alone for analgesia. Both groups were treated for 7 consecutive days. The two groups were compared in pain degree (visual analog scale (VAS) score) after operation and hip joint function (Harris score), daily living ability (modified Barthel index (MBI) score), bone metabolism-related indexes, and inflammatory factors before and after treatment. RESULTS: At 1-7 d after operation, both groups had gradually lower VAS scores, and at 5 and 7 d after operation, the Obs group had a lower VAS score than the Con group (both P<0.05). Additionally, at 2 months after operation, both groups had higher Harris scores and MBI scores, and the scores of the Obs group were both higher than those of the Con group (both P<0.05). At 7 d after operation, both groups showed a decrease in serum beta collagen degradation products (ß-CTx) and an increase in procollagen type I amino-terminal propeptide (PINP) (both P<0.05), but the differences between the two groups in ß-CTx and PINP were insignificant (P>0.05). Moreover, at 7 d after operation, both groups showed a decrease in C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α), and the two levels in the Obs group were lower than those in the Con group (both P<0.05). CONCLUSION: For elderly patients with intertrochanteric fracture, AGTF combined with acupuncture at the Xuehai acupoint can more effectively relieve their postoperative pain and postoperative inflammation and more strongly promote their postoperative recovery of hip joint function.

Effect of exogenous glutathione supplementation on the in vitro developmental competence of ovine oocytes.

The beneficial effect of glutathione (GSH) on the in vitro maturation (IVM) of bovine/porcine oocytes has been confirmed; however, the antioxidant effect of exogenous GSH supplementation on the IVM of ovine oocytes has not been determined. In this study, ovine cumulus oocyte complexes (COCs) were classified into three groups according to the layer number of cumulus cells (the Grade A group has more than five layers, the Grade B group has three to four layers and the Grade C group has less than three layers). After in vitro culture of COCs in the presence of exogenous GSH, the meiotic competence of ovine oocytes was assessed by analyzing nuclear maturation to metaphase II (MII) stage, cortical granules (CGs) dynamics, astacin like metalloendopeptidase (ASTL) distribution, histone methylation pattern, reactive oxygen species (ROS) production, mitochondrial activities and genes expression. After in vitro fertilization (IVF), assessments of embryonic development were conducted to confirm the effects of exogenous GSH supplementation. The results showed that exogenous GSH not only enhanced the maturation rates of the Grade B and Grade C groups but also promoted CGs dynamics and ASTL distribution of the Grade A, B and C groups (p < 0.05). Exogenous GSH increased the mitochondrial activities of the Grade A, B and C groups and decreased the ROS production levels of oocytes (p < 0.05), regardless of the layer number of cumulus cells. Moreover, exogenous GSH promoted the expression levels of genes related with oocyte maturation, antioxidant activity and antiapoptotic effects in the Grade B and Grade C groups (p < 0.05). The expression levels of H3K4me3 and H3K9me3 in the Grade B and Grade C groups were promoted after exogenous GSH supplementation (p < 0.05), consistent with the expression levels of genes related with histone methylation (p < 0.05). In addition, exogenous GSH strongly promoted the embryonic developmental competence of Grade B and Grade C groups (p < 0.05). Taken together, our findings provide foundational evidence for the free radical scavenging potential of exogenous GSH in the in vitro developmental competence of ovine oocytes, especially oocytes from COCs lacking cumulus cells. These findings, which demonstrated the potential for improving the quality of ovine oocytes during IVM, will contribute to researches on GSH applications and the efficiency of assisted reproductive technology for ovine breeding.

[Kinesio Taping combined with electroacupuncture for the treatment of patellofemoral disorder in middle-aged and elderly exercise enthusiasts].

OBJECTIVE: To observe the clinical efficacy of Kinesio Taping combined with electroacupuncture in the treatment of patellofemoral disorder in middle-aged and elderly exercise enthusiasts. METHODS: From April 2018 to April 2020, 62 middle-aged and elderly exercisers with patellofemoral disorder were selected and divided into observation group and control group. In the observation group, there were 30 cases:12 males and 18 females, aged from 35 to 66 years old, with an average age of (48.32±6.80) years old. The observation group was treated with Kinesio Taping and electroacupuncture . In the control group, there were 32 cases:12 males and 20 females, aged from 35 to 67 years old, with an averageage of (48.67±8.13) years old. The patients in the control group was treated with knee electroacupuncture. All the patients in both groups were treated once every other day, 3 times a week, for a total of 4 weeks. The VAS pain score and knee Lysholm score before and after treatment were compared between the two groups before and after treatment, and statistical analysis was conducted. RESULTS: In the control group, 2 patients were not satisfied with the curative effect after 2 weeks of treatment and gave up treatment, while the remaining 60 patients completed all the treatments. After 4 weeks of treatment, the VAS and Lyshlom scores of the control group were 2.73±1.46 and 75.63±8.62 respectively;the VAS and Lyshlom scores of the observation group were 2.02±1.85 and 83.31±5.53 respectively;the VAS and Lyshlom scores of the observation group and the control group were better than those before treatment, and the Lyshlom scores of the observation group were better than those of the control group. CONCLUSION: Kinesio Taping combined with electroacupuncture is aimed at patellofemoral disorderof middle-aged and elderly sports enthusiasts. It has little trauma, can relieve pain and has a fast onset speed, which is readily accepted by patients, and promotes the rehabilitation of knee joint function of patients, thus providing a favorable reference for the promotion in clinical application.

Gracillin Isolated from Reineckia carnea Induces Apoptosis of A549 Cells via the Mitochondrial Pathway.

BACKGROUND: Reineckia carnea is commonly used to treat cough, pneumonia and other diseases in China. In our previous study, it was found that the ethanol extracts of Reineckia carnea have a strong inhibitory effect on the proliferation of human lung cancer A549 cells. Here, we isolated gracillin from ethanol extracts for the first time. PURPOSE: Clarify the antiproliferation effect of gracillin on A549 cells and further explore its mechanisms via the mitochondrial pathway. METHODS: Gracillin was isolated and purified by silica gel, D-101 macroporous resin and preparative RP-HPLC, then identified by NMR and HR-MS. The inhibitory effects of gracillin on the proliferation of A549 cells were detected by the MTS method. Its mechanisms were further explored by flow cytometry and Western blot. RESULTS: A steroid saponin, gracillin, was isolated and identified from Reineckia carnea for the first time. In a concentration-dependent and time-dependent manner, gracillin significantly inhibited the proliferation of A549 cells with an IC50 value at 2.54 µmol/L and induced morphological changes. The results of flow cytometry analysis showed that the apoptosis rate of A549 cells was significantly increased (p < 0.05), and the cells proportion was obviously arrested in S phase. The concentration of intracellular calcium was raised (p < 0.01), and the mitochondrial membrane potential was greatly decreased (p < 0.01). In addition, the expression levels of Bax, caspase-3, cleaved caspase-3, and cytochrome C were dramatically up-regulated while Bcl-2 was down-regulated (p < 0.05) in A549 cells. CONCLUSION: This study confirmed that gracillin has a significant antiproliferative effect on A549 cells. Gracillin could induce the apoptosis of A549 cells through the mitochondrial pathway, which might be associated with regulation of the concentration of intracellular calcium, the mitochondrial membrane potential and the expression levels of Bax, Bcl-2, caspase-3, cleaved caspase-3, and cytochrome C.

Transcription factor CsDOF regulates glutamine metabolism in tea plants (Camellia sinensis).

Glutamine plays a critical role in ammonium assimilation, and contributes substantially to the taste and nutritional quality of tea. To date, little research has been done on glutamine synthesis in tea plants. Here, a zinc finger protein CsDOF and a glutamine synthetase (GS)-encoding gene CsGS2 from tea plant (Camellia sinensis cv 'Shuchazao') were characterized, and their role in glutamine biosynthesis was determined using transient suppression assays in tea leaves and overexpression in Arabidopsis thaliana. The expression patterns of CsDOF and CsGS2, the GS activity and the glutamine content of photosynthetic tissues (leaf and bud) were significantly induced by shade. Suppressing the expression of CsDOF resulted in downregulated expression of CsGS2 and reduction of the leaf glutamine content. Moreover, in CsDOF-silenced plants, the expression of CsDOF and the glutamine content under shade treatment were higher than in natural light. The glutamine content and CsGS2 transcript level were also decreased in tea leaves when CsGS2 was suppressed, while they were higher under shade treatment than in natural light in CsGS2-silenced plants. In addition, the glutamine content and GS2 transcript level were increased when CsDOF and CsGS2 was overexpressed in Arabidopsis thaliana, respectively. In binding analyses, CsDOF directly bound to an AAAG motif in the promoter of CsGS2, and promotes its activity. The study shed new light on the molecular mechanism by which CsDOF activates CsGS2 gene expression and contributes to glutamine biosynthesis in tea plants.