Efficacy of growth factor gene-modified stem cells for motor function after spinal cord injury in rodents: a systematic review and meta­analysis.

The efficacy of growth factor gene-modified stem cells in treating spinal cord injury (SCI) remains unclear. This study aims to evaluate the effectiveness of growth factor gene-modified stem cells in restoring motor function after SCI. Two reviewers searched four databases, including PubMed, Embase, Web of Science, and Scopus, to identify relevant records. Studies on rodents assessing the efficacy of transplanting growth factor gene-modified stem cells in restoring motor function after SCI were included. The results were reported using the standardized mean difference (SMD) with a 95% confidence interval (95% CI). Analyses showed that growth factor gene-modified stem cell transplantation improved motor function recovery in rodents with SCI compared to the untreated (SMD = 3.98, 95% CI 3.26-4.70, I2 = 86.8%, P < 0.0001) and stem cell (SMD = 2.53, 95% CI 1.93-3.13, I2 = 86.9%, P < 0.0001) groups. Using growth factor gene-modified neural stem/histone cells enhanced treatment efficacy. In addition, the effectiveness increased when viral vectors were employed for gene modification and high transplantation doses were administered during the subacute phase. Stem cells derived from the human umbilical cord exhibited an advantage in motor function recovery. However, the transplantation of growth factor gene-modified stem cells did not significantly improve motor function in male rodents (P = 0.136). Transplantation of growth factor gene-modified stem cells improved motor function in rodents after SCI, but claims of enhanced efficacy should be approached with caution. The safety of gene modification remains a significant concern, requiring additional efforts to enhance its clinical translatability.

Effect of Yiyuan moxibustion on urodynamics and TRPV4/ATP/P2X5 signal pathway of bladder tissue in rats with neurogenic bladder after sacral cord injury. / ç›Šå ƒç¸å¯¹éª¶é«“æŸä¼¤åŽç¥žç»æºæ€§è†€èƒ±å¤§é¼ å°¿æµåŠ¨åŠ›å­¦åŠè†€èƒ±ç»„ç»‡TRPV4/ATP/P2X5信号通路的影响.

OBJECTIVES: To observe the effect of Yiyuan moxibustion on urodynamics and the expressions of transient receptor potential vanilloid 4 (TRPV4), adenosine triphosphate (ATP), tyrosine protein kinase KIT (C-Kit) and adenosine triphosphate receptor P2X5 in bladder tissue of rats with detrusor reflex-free neurogenic bladder (NB) after sacral cord injury (SCI), so as to explore its mechanism in promoting the recovery of urination function of NB rats. METHODS: Female SD rats were randomly divided into sham operation, model, Yiyuan moxibustion, Yiyuan moxibustion+inhibitor (combination) and inhibitor groups, with 12 rats in each group. The model of detruser reflex-free NB after sacral SCI was established by modified Hassan Shaker spinal cord transection method. The behavioral score of Basso Beasttie Bresnahan (BBB) and urodynamic indexes were used to evaluate the model of rats after operation. Fifteen days after modeling, Yiyuan moxibustion was applied to "Shenque" (CV8) and "Guanyuan" (CV4) for 20 min, once daily for 14 days. Rats of the inhibitor and combination groups were given intravesical instillation of HC067047 (1 mL, 1 µmol/L, 30 min). After the interventions, urodynamics was used to evaluate the bladder function of rats. HE staining was used to observe the morphology of bladder tissue. ATP content in bladder tissue was detected by colorimetric method. The positive expression rates of C-Kit and their receptor P2X5 in bladder tissue were observed by immunofluorescence double labeling method, and TRPV4, C-Kit, and P2X5 protein expression levels in bladder tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the maximum bladder capacity and bladder compliance of rats in the model group were increased (P<0.01), the leak point pressure, ATP content, the possitive expression rates of C-Kit and P2X5, and the protein expression levels of TRPV4, C-Kit, P2X5 in bladder tissue were decreased (P<0.01). In comparison with the model and combination groups, the Yiyuan moxibustion group showed a decrease in maximum bladder capacity and bladder compliance (P<0.01), an increase in leakage point pressure, ATP content, the possitive expression rates of C-Kit and P2X5, and TRPV4, C-Kit, and P2X5 protein expression levels (P<0.01, P<0.05)；However, these indicators showed opposite trends in the inhibitor group (P<0.01, P<0.05). CONCLUSIONS: Yiyuan moxibustion can improve the urodynamics and bladder function in rats with bladder detrusor nonreflective after SCI, which may be related to its effect in activating the TRPV4 channel in bladder tissue, promoting the release of ATP from bladder epithelium, thus increasing the expression of bladder Cajal interstitial cells and their purinergic P2X5 receptors.

Derivation and Validation of a Risk Score for Methicillin-Resistant Staphylococcus aureus Bloodstream Infection.

BACKGROUND: Compared with methicillin sensitive Staphylococcus aureus (MSSA), the prognosis of patients with methicillin resistant Staphylococcus aureus (MRSA) bloodstream infection is poor. Therefore, the construction of MRSA and MSSA identification model has certain value for the selection of antibiotics and treatment outcome control. This study aimed to derive and validate a simple risk prediction model for MRSA bloodstream infection in Chinese patients. METHODS: Three hundred and thirty-five patients with Staphylococcus aureus (S. aureus) bloodstream infection were retrospectively analyzed and divided into three groups. The first group was used for the risk score derivation (n = 163), the second group was used for internal validation (n = 80), and the third group was used for external validation (n = 92). According to the odds ratio (OR) obtained from multivariate logistic regression, the risk prediction model for MRSA bloodstream infection was established, and the prediction efficiency of the model in three cohorts were evaluated. RESULTS: Hospital stay before BSI ≥ 7 days, hospital acquired BSI, infection source ≥ 2 sites, indwelling gastric tube before BSI and carbapenems used before BSI and after admission were independent influencing factors of MRSA in the derivation group, the above influencing factors were scored 3, 5, 4, 3, and 3, respectively. The derivation, internal and external validation groups showed adequate discrimination (the AUCs were 0.788, 0.780, and 0.742, respectively) and good calibration (H-L tests were χ2 = 3.896, p = 0.306; χ2 = 4.221, p = 0.298; and χ2 = 3.974, p = 0.352, respectively). The risk scores were further divided into very low-risk (score 0 - 3), low-risk (score 4 - 7), high-risk (score 8 - 12), and very high-risk (score ≥ 13) layers. CONCLUSIONS: The simple risk score model for predicting MRSA bloodstream infection has good predictive effect, high predictive accuracy, and good clinical applicability, which can help clinicians choose sensitive antibiotics and reduce the adverse prognosis of patients.

[Efficacy differences between electroacupuncture and moxibustion for neurogenic bladder after spinal cord injury: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between electroacupuncture(EA) and moxibustion for neurogenic bladder (NB) after spinal cord injury (SCI). METHODS: One hundred and twenty patients with NB after SCI were randomly divided into an EA group, a moxibustion group, and an intermittent catheterization group, with 40 patients in each group. The patients in the intermittent catheterization group were treated with routine treatment and intermittent catheterization, while the patients in the EA group and the moxibustion group were treated with additional treatments of EA (discontinuous wave, with a frequency of 1.3-1.6 Hz, and intensity based on patient tolerance) and moxibustion, respectively. The acupoints used in both groups were Zhongji (CV 3) and Guanyuan (CV 4), bilateral Zusanli (ST 36), Yinlingquan (SP 9), and Baliao points. Each session lasted for 30 min, once daily, six times a week, for a total of six weeks.The maximum bladder capacity (MBC), residual urine vdume (RUV), detrusor pressure (Pdet) during the filling phase, bladder compliance (BC), maximum renal pelvis separation width of both kidneys, urine white blood cell count, TCM syndrome score, and World Health Organization quality of life assessment-BREF (WHOQOL-BREF) score were compared before and after treatment in the 3 groups. The number of patients in each group who achieved bladder functional balance was recorded, and the clinical efficacy was assessed after treatment. RESULTS: After treatment, the MBC, Pdet, BC, and WHOQOL-BREF scores in the EA group and the moxibustion group were increased (P<0.05), while the RUV, maximum renal pelvis separation width of both kidneys, urine white blood cell count, and TCM syndrome scores were decreased (P<0.05, P<0.01). In the intermittent catheterization group, MBC, RUV, maximum renal pelvis separation width of both kidneys, and urine white blood cell count were decreased (P<0.05), while BC and WHOQOL-BREF score were increased (P<0.05) after treatment. After treatment, the MBC, Pdet, BC, and WHOQOL-BREF scores in the EA group and the moxibustion group were higher than those in the intermittent catheterization group (P<0.05), while the RUV and TCM syndrome scores were lower than those in the intermittent catheterization group (P<0.05). Moreover, after treatment, the MBC and Pdet in the moxibustion group were higher than those in the EA group (P<0.05), while the RUV, maximum renal pelvis separation width of both kidneys, and TCM syndrome score in the EA group were lower than those in the moxibustion group (P<0.05). The number of patients who achieved bladder functional balance after treatment in the EA group and the moxibustion group was higher than that in the intermittent catheterization group (P<0.05). The cured and effective rate was 85.0% (34/40) in the EA group and 82.5% (33/40) in the moxibustion group, which were both higher than 65.0% (26/40) in the intermittent catheterization group (P<0.05), there was no significant difference between the EA group and the moxibustion group (P>0.05). CONCLUSION: EA and moxibustion could effectively improve the functional state of bladder in patients with NB after SCI. EA is more effective in reducing residual urine volume and excessive activity of the urethral sphincter, and relieving TCM syndromes, while moxibustion is more effective in increasing the pressure of the detrusor during the filling period and establishing the detrusor reflex.

Heteronuclear Trimetallic MFe2 and M2 Fe (M=V, Nb, and Ta) Clusters for Dinitrogen Activation.

Catalysts with heteronuclear metal active sites may have high performance in the nitrogen reduction reaction (NRR), and the in-depth understanding of the reaction mechanisms is crucial for the design of related catalysts. In this work, the dissociative adsorption of N2 on heteronuclear trimetallic MFe2 and M2 Fe (M=V, Nb, and Ta) clusters was studied with density functional theory calculations. For each cluster, two reaction paths were studied with N2 initially on M and Fe atoms, respectively. Mayer bond order analysis provides more information on the activation of N-N bonds. M2 Fe is generally more reactive than MFe2 . The coordination mode of N2 on three metal atoms can be end-on: end-on: side-on (EES) for both MFe2 and M2 Fe. In addition, a unique end-on: side-on: side-on (ESS) coordination mode was found for M2 Fe, which leads to a higher degree of N-N bond activation. Nb2 Fe has the highest reactivity towards N2 when both the transfer of N2 and the dissociation of N-N bonds are taken into account, while Ta-containing clusters have a superior ability to activate the N-N bond. These results indicate that it is possible to improve the performance of iron-based catalysts by doping with vanadium group metals.

Mechanisms of lipid metabolism promoted by berberine via peroxisome proliferator-activated receptor gamma during in vitro maturation of porcine oocytes.

This study was conducted to explore the molecular mechanisms of berberine (Ber) via peroxisome proliferator-activated receptor gamma (PPARG) in promoting in vitro maturation (IVM) and lipid metabolism of porcine oocytes. Our results showed that expression changes in PPARG influenced IVM and the lipid droplet content of porcine oocytes. Moreover, c-Jun-N-terminal kinase (JNK) inhibitor modified the effect of PPARG agonist on IVM and lipid droplet content of porcine oocytes, and Ber significantly reduced lipid droplet content. Activation of PPARG upregulated the transcription level of microRNA-192 (miR-192), significantly promoted the expression of fatty acid binding protein 3 (FABP3) and steroid regulatory element binding transcription factor 1 (SREBF1) and PPARG, inhibited phosphorylation of PPARG, and enhanced JNK phosphorylation. Ber and overexpression of miR-192 upregulated the transcription level of miR-192 in porcine oocytes; significantly decreased the expression of FABP3, SREBF1, and PPARG; increased PPARG phosphorylation; and inhibited JNK phosphorylation. Otherwise, JNK inhibitor reduced the effects of PPARG agonist. In conclusion, Ber may activate the expression of miR-192, downregulate the expression level of PPARG and lipid synthesis-related genes, increase PPARG phosphorylation, and reduce JNK phosphorylation to enhance lipid metabolism, which is beneficial to improve porcine oocyte quality of IVM.

Reparative effects of lycium barbarum polysaccharide on mouse ovarian injuries induced by repeated superovulation.

To explore the repair effect of lycium barbarum polysaccharide (LBP) on ovarian injuries induced by repeated superovulation in mice, a model of ovarian injury was established, and ovarian repair was assessed after intragastric administration of LBP. The oocyte quality and blastocyst rates of pronuclear embryos in vitro were observed. The levels of 8-hydroxydeoxyguanosine (8-OHdG) and lipid peroxide (LPO) in ovarian tissue were measured, and ovarian damage was assessed in paraffin sections. The groups with significant injury were selected according to the above observation, mice in the significant injury group were intragastrically administered with LBP (low dose, 25 mg/kg; medium dose, 35 mg/kg; and high dose, 45 mg/kg) for 30 days. The above measurements and anti-Müllerian hormone (AMH) expression were detected in the mouse ovaries and the breeding verification was carried out. Our results showed that repeated superovulation could cause mouse oocyte quality to drop, significant differences started from 4 superovulation events (P < 0.05). The levels of 8-OHdG and LPO in the ovary increased gradually as the number of superovulation events increased, and significant differences were observed after 4-6 superovulations (P < 0.05). The ratios of primordial follicles, primary, tertiary and mature follicles decreased and the ratio of atresia follicles increased as the number of superovulation events increased, especially in 4-6 superovulation groups. Thus, the groups of superovulation 4-6 events were considered as significant injury groups. LBP-medium dose groups significantly improved the number and quantity of oocytes and embryo blastocyst rate (P < 0.05), significantly decreased 8-OHdG and LPO levels in mice ovary (P < 0.05), also improved the ratios of all stages follicles and reduced the rate of atresia follicles, increased the numbers of litter size, live birth, weaning survival, and repaired the expression of AMH in ovary significantly (P < 0.05). In conclusion, the degree of ovarian injury was affected by the number of superovulation. LBP repaired ovarian injuries most likely through scavenging oxidative products 8-OHdG and LPO and increasing AMH protein expression.

Effects of icariin on ovarian function in d-galactose-induced aging mice.

In this study, effects of icariin (Ica) on were examined in a mouse model of d-galactose (D-gal)-induced ovarian aging. Kunming white mice were divided into three groups: aging group induced with D-gal, experiment group treated with Ica at low (50 mg/kg), middle (100 mg/kg) and high (200 mg/kg) concentrations, and control group with no treatment. Ovarian histomorphology, serum FSH, LH and E2 levels, and reproductive function were compared among the groups. Ovarian expression of Amh, Bax and Bcl-2 was examined by qPCR and western blotting. Our results showed that diameters of secondary and tertiary follicles were significantly reduced in the aging group when compared with control group (P < 0.01), and were restored to normal in Ica 100 and Ica 200 treatment groups. The diameter of atretic follicles was significantly smaller in the aging group compared with control group and Ica 200 treatment group (P < 0.05). The proportion of secondary and atretic follicles was higher in the aging group compared with control group, Ica 100 and 200 treatment groups, whereas the proportion of tertiary and mature follicles was reduced in the aging group versus control, Ica 100 and 200 groups. The aging group lacked mature follicles, whereas Ica treatment induced mature follicle development. Primary and secondary follicles exhibited similar theca cell numbers and theca interna and externa cell layers in all groups examined, whereas theca interna and externa cell layers were decreased and increased, respectively, in tertiary follicles of aging group compared with control and I 200 groups. In the aging group, FSH and LH levels were significantly higher than those in control and Ica 200 groups (P < 0.05), and the E2 level was significantly reduced compared with control (P < 0.01), Ica 200 (P < 0.01), and Ica 100 (P < 0.05) groups. Serum hormone levels were equivalent in the control, Ica 100 and Ica 200 groups. The pregnancy rate was reduced in the aging group compared with other groups. The average litter size per birth, birth litter weight, and weaning weight of litters were all significantly lower in the aging group compared with control, Ica 100 and 200 groups (P < 0.05). The ovarian expression of AMH and Bcl-2 mRNA was significantly reduced in the aging group compared with those in control and Ica-treated groups (P < 0.01). In contrast, Bax expression was significantly higher in the aging group compared with all other groups (P < 0.01), and the Bcl-2/Bax ratio was markedly reduced in aging group compared with control, Ica 100 and 200 groups (P < 0.01), and Ica 50 group (P < 0.05). Ovarian expression of AMH protein was elevated in the Ica 100 group compared with the aging, control and Ica 50 groups (P < 0.01) and Ica 200 group (P < 0.05). Ovarian Bcl-2 protein levels and the Bcl-2/Bax ratio were significantly higher in the Ica 100 group than those in the Ica 50, 200 and aging groups (P < 0.05), and were similar or reduced (P < 0.05), respectively, compared to those in control group. Ovarian Bax expression was similar in each group. These findings suggest that Ica can improve ovarian follicular development, inhibit follicular atresia, decrease FSH and LH levels and increase E2, upregulate ovarian AMH expression and increase the Bcl-2/Bax ratio in aging mice. Therefore, Ica can partially restore ovarian function of aging mice and enhance their fertility. Optimal reproductive effects were obtained with the Ica 100 group.

Function of berberine on porcine in vitro fertilization embryo development and differential expression analysis of microRNAs.

The effect of berberine (Ber) on in vitro fertilization (IVF) embryo development in pigs and the associated differential expression of microRNAs (miRNAs) in the embryo were investigated. NCSU-23 embryonic culture medium was used for a control group, while NCSU-23 embryonic culture medium added with Ber was used for a Ber group. The embryo development rates in these groups were determined, and the zygotes, 4- and 8-cell embryos, and blastocysts were collected for cDNA microarray analysis. The development rates of 2-, 4-, 8-cell embryos and blastocysts were significantly higher in the Ber group than those in the control group (p < 0.01). The differentially expressed miRNAs in the 8-cell versus the 4-cell stage in control group as well as in the 8-cell Ber group versus the 8-cell control group overlapped, and it was found that nine miRNAs were commonly upregulated and two of them were downregulated, while there was no overlap among the other groups. The target genes of Ber-regulated miRNAs at the 8-cell stage were mainly associated with the molecular pathway of nucleic acid and protein synthesis. These findings suggest that Ber may regulate the expression of miRNAs at the 8-cell stage, which is beneficial to provide material reserves for the maternal to zygote transition of porcine embryos, thereby increasing the porcine IVF embryo development rate.