Lei's formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments.

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H2O2-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

Reference values of gait parameters in healthy Chinese university students: A cross-sectional observational study.

BACKGROUND: Gait is influenced by race, age, and diseases type. Reference values for gait are closely related to numerous health outcomes. To gain a comprehensive understanding of gait patterns, particularly in relation to race-related pathologies and disorders, it is crucial to establish reference values for gait in daily life considering sex and age. Therefore, our objective was to present sex and age-based reference values for gait in daily life, providing a valuable foundation for further research and clinical applications. AIM: To establish reference values for lower extremity joint kinematics and kinetics during gait in asymptomatic adult women and men. METHODS: Spatiotemporal, kinematics and kinetics parameters were measured in 171 healthy adults (70 males and 101 females) using the computer-aided soft tissue foot model. Full curve statistical parametric mapping was performed using independent and paired-samples t-tests. RESULTS: Compared with females, males required more time (cycle time, double-limb support time, stance time, swing time, and stride time), and the differences were statistically significant. In addition, the step and stride lengths of males were longer. Compared to males, female cadence was faster, and statures-per-second and stride-per-minute were higher. There were no statistical differences in speed and stride width between the two groups. After adjusting for height, it was observed that women walked significantly faster than men, and they also had a higher cadence. However, in terms of step length, stride length, and stride width, both genders exhibited similarities. CONCLUSION: We established reference values for gait speed and spatiotemporal gait parameters in Chinese university students. This contributes to a valuable database for gait assessment and evaluation of preventive or rehabilitative programs.

Relationship between size and location of infarction beside lateral ventricle and motor recovery following rehabilitation.

BACKGROUND: The lesions besides lateral ventricle and motor recovery following rehabilitation have hardly been studied. OBJECTIVE: To explore the relationship between the size, location of infarction beside the lateral ventricle and motor recovery following rehabilitation. METHODS: A prospective cohort of 55 patients submitted to a Rehabilitation Medical Center between January 2015 and June 2019 who suffered a single cerebral infarction beside the lateral ventricle were included in the study. The size and distance between the posterior margin and the frontal-middle line (FML) of the lesion were measured. Follow-up was conducted until the recovery was no longer progressing. Barthel index and Brunstrom stages were used to evaluate the outcome (full recovery, partial recovery and poor recovery). Variance analysis and nonparametric test were used for the comparison between groups. Multivariate logistic regression analysis was used to screen the factors affecting the outcomes. The Pearson correlation coefficient was used to compare the volume of infarction, behind the FML and the outcomes. RESULTS: Among the 55 patients, the outcome was full recovery (n = 28), partial recovery (n = 13) and poor recovery (n = 14). Multivariate logistic regression analysis showed that volume and location of the infarction were significantly correlated with the outcome (p = 0.039, 0.050). The lesion volume in the full recovery patients was significantly smaller than that in the poor recovery patients (p < 0.01). The posterior edge of the lesion in the full recovery patients behind the FML was statistically significant compared with that in the poor recovery patients (p < 0.01). Spearman correlation analysis showed that the motor recovery was negative correlation to lesion volume (r = -0.508, P < 0.01) and location (r = -0.450, P < 0.01) of the infarction. CONCLUSION: The motor recovery of patients with cerebral infarction beside lateral ventricle is related to the volume and location of the lesion. The larger the volume of the lesion, and the farther the posterior margin of the lesion to the FML, the worse the motor recovery.

An LC-APCI+-MS/MS-based method for determining the concentration of neurosteroids in the brain of male mice with different gut microbiota.

BACKGROUND: Although the interaction between the gut microbiota and central nervous system (CNS) is well-known, the effects of gut microbiota on different brain regions remain obscure. NEW METHOD: In present study, we developed a simple and sensitive high-performance liquid chromatography-tandem mass spectrometry with atmospheric pressure chemical ionization in positive mode (LC-APCI+-MS/MS) for simultaneous detection of 12 analytes in the rodent' brain with different housing conditions RESULTS: The results showed that male mice in XZ group had significantly higher brain levels of dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T), progesterone (P), corticosterone (CORT), aldosterone (ALD) and 11-dehydrocorticosterone (11-DHC) than those in SPF group. CORT level was higher in the left prefrontal cortex, whereas ALD and 11-DHC levels were higher in the left hypothalamus than in the right symmetrical areas in both groups. DHEA and CORT levels were highest in the striatum than in the prefrontal cortex, hippocampus, hypothalamus, regardless of the region and group (XZ and SPF). COMPARISON WITH EXISTING METHODS: These results demonstrated that the method developed in this study provides, for the first time, direct quantitation of neurosteroids in male mice brain. CONCLUSIONS: DHEA levels showed a left-lateralized pattern in the hippocampus and hypothalamus. Mice in the XZ group showed significantly elevated levels of CORT and/or its metabolites, ALD and 11-DHC in brain than mice in the SPF group. Insanitation living conditions increased more diverse gut microbiota.

Identification of the AQP8-miR-92a network associated with the aggressive traits of colorectal cancer.

Even though earlier reports have revealed that Aquaporin 8 (AQP8) exert essential roles in diverse malignancies, its relationship between specific microRNAs (miRNAs) in regulation of colorectal carcinoma (CRC) progression has never been elaborated. Herein, we proved that AQP8 was downregulated in CRC and high level of AQP8 was significantly associated with better survival in CRC patients. Overexpression of AQP8 restrained CRC cell proliferation, migration and invasion capacities in vitro. In vivo, upregulation of AQP8 also suppressed CRC cell growth. Mechanistic analyses illustrated that AQP8 was a directly target of miR-92a. The expression of AQP8 was negatively modulated by miR-92a. Rescues analysis indicated that miR-92a facilitated CRC cell growth and invasion via modulating the expression of AQP8. Our work validated that miR-92a regulated the aggressiveness of CRC cell via targeting AQP8.

Characterization of the complete chloroplast genome of Ligusticum sinense, as a Chinese herb to treat toothache in China.

Ligusticum sinense is a popular herb in Chinese medicine. The circular double-stranded complete chloroplast genome of L. sinense was 146,342 bp in length, exhibiting a typical quadripartite structure. It contained a large single-copy region (LSC) of 91,788 bp, a small single-copy region (SSC) of 17,618 bp and two identical inverted repeat (IR) regions of 18,468 bp each. The overall nucleotide composition of chloroplast genome sequence is: A (30.8%), T (31.6%), C (19.2%), G (19.4%) and the total G + C content of 38.6%. The chloroplast genome contained 127 genes, including 83 protein-coding genes, 36 transfer RNA genes and 8 ribosomal RNA genes were annotated. The total of 15 genes duplicated in one of the IR, including 6 tRNA, 4 rRNA, and 5 protein-coding genes. The ML phylogenetic tree indicated that L. sinense is closely related to L. tenuissimum in the phylogenetic relationship.

Prostaglandin E1 attenuates high glucose-induced apoptosis in proximal renal tubular cells by inhibiting the JNK/Bim pathway.

Proximal renal tubular damage is a critical process underlying diabetic kidney disease (DKD). Our previous study shows that prostaglandin E1 (PGE1) reduces the apoptosis of renal tubular cells in DKD rats. But its underlying mechanisms remain unclear. In this study we investigated the protective effects of PGE1 in DKD rats and high glucose (HG, 30 mM)-treated HK-2 proximal tubular cells. Four weeks after uninephrectomized streptozotocin-induced diabetic rats were established, the DKD rats were administered PGE1 (10 µg· kg-1· d-1, iv.) for 10 consecutive days. We showed that PGE1 administration did not change blood glucose levels, but alleviated diabetic kidney injury in the DKD rats, evidenced by markedly reduced proteinuria and renal tubular apoptosis. In the in vitro experiments, PGE1 (0.1-100 µM) significantly enhanced HG-reduced HK-2 cell viability. In HG-treated HK-2 cells, PGE1 (10 µM) significantly suppressed the c-Jun N-terminal kinase (JNK) and the mitochondrial apoptosis-related protein expressions such as Bim, Bax, caspase-3 and cleaved caspase-3; similar changes were also observed in the kidney of PGE1-treated DKD rats. By using two pharmacological tools-JNK activator anisomycin (AM) and JNK inhibitor SP600125, we revealed that PGE1 blocked HG-triggered activation of JNK/Bim pathway in HK-2 cells; JNK was an upstream regulator of Bim. In conclusion, our results demonstrate that the nephroprotective effects of PGE1 against apoptosis of proximal renal tubule in DKD rats via suppressing JNK-related Bim signaling pathway.

Quantum chemical study of adsorption and dissociation of H2S on the gallium-rich GaAs (001)-4 x 2 surface.

H(2)S adsorption and dissociation on the gallium-rich GaAs(001)-4 x 2 surface is investigated using hybrid density functional theory. Starting from chemisorbed H(2)S on the GaAs(001)-4 x 2 surface, two possible reaction routes have been proposed. We find that H(2)S adsorbs molecularly onto GaAs(001)-4 x 2 via the formation of a dative bond, and this process is exothermic with adsorption energy of 6.6 kcal/mol. For the first reaction route, one of the H atoms from the chemisorbed H(2)S is transferred to a second-layer As atom and the dissociated SH is inserted into the Ga-As bond with an activation barrier of 8.2 kcal/mol, which is found to be 29.3 kcal/mol more stable than the reactants. For the second case, the dissociated species may insert themselves into the Ga-Ga dimer resulting in the Ga-H-Ga and Ga-HS-Ga bridge-bonded states, which are found to be 29.8 and 22.2 kcal/mol more stable than the reactants, respectively. However, the calculations also show that the activation barrier (16.1 kcal/mol) for chemisorbed H(2)S dissociation through the second route is higher than the transfer of one H atom into a second-layer As atom. As a result, we conclude that sulfur insertion into the Ga-As bond is more kinetically favorable.

Quantum chemical study of the initial surface reactions in atomic layer deposition of TiN on the SiO(2) surface.

Cluster calculations employing hybrid density functional theory have been carried out to examine the initial surface reactions in atomic layer deposition (ALD) of TiN thin films on the SiO(2) surface using TiCl(4) and NH(3) as precursors. The potential energy surface (PES) of both half-reactions at different temperatures is presented. The first half-reaction between TiCl(4) with the SiO(2) surface is activated with an activation barrier of 0.78 eV and an exothermicity of 0.38 eV, suggesting that it is thermodynamically favourable. Also, the NH(3) half-reaction begins with the formation of amido complexes by the replacement of Cl atoms by NH(2), which is endothermic by 0.58 eV with a physisorbed HCl state (HCl-PS1). Formation of the amido complexes can be followed by an elimination reaction to form imido complexes, which has a relatively high activation barrier of 2.51 eV. In addition, the effect of the reaction temperature on the Cl impurity concentrations and film growth rate in the ALD process is also discussed.