The Role of P53 in Myocardial Ischemia-Reperfusion Injury.

PURPOSE: P53 is one of the key tumor suppressors. In normal cells, p53 is maintained at low levels by the ubiquitination of the ubiquitinated ligase MDM2. In contrast, under stress conditions such as DNA damage and ischemia, the interaction between p53 and MDM2 is blocked and activated by phosphorylation and acetylation, thereby mediating the trans-activation of p53 through its target genes to regulate a variety of cellular responses. Previous studies have shown that the expression of p53 is negligible in normal myocardium, tends to increase in myocardial ischemia and is maximally induced in ischemia-reperfused myocardium, demonstrating a possible key role of p53 in the development of MIRI. In this review, we detail and summarize recent studies on the mechanism of action of p53 in MIRI and describe the therapeutic agents targeting the relevant targets to provide new strategies for the prevention and treatment of MIRI. METHODS: We collected 161 relevant papers mainly from Pubmed and Web of Science (search terms "p53" and "myocardial ischemia-reperfusion injury"). After that, we selected pathway studies related to p53 and classified them according to their contents. We eventually analyzed and summarized them. RESULTS AND CONCLUSION: In this review, we detail and summarize recent studies on the mechanism of action of p53 in MIRI and validate its status as an important intermediate affecting MIRI. On the one hand, p53 is regulated and modified by multiple factors, especially non-coding RNAs; on the other hand, p53 regulates apoptosis, programmed necrosis, autophagy, iron death and oxidative stress in MIRI through multiple pathways. More importantly, several studies have reported medications targeting p53-related therapeutic targets. These medications are expected to be effective options for the alleviation of MIRI, but further safety and clinical studies are needed to convert them into clinical applications.

[Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version)].

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

Regulatory role of miR-129 and miR-384-5p on apoptosis induced by oxygen and glucose deprivation in PC12 cell.

This study aimed to establish the role of miR-129 and miR-384-5p in cerebral ischemia-induced apoptosis. Using PC12 cells transfected with miR-129 or miR-384-5p mimics or inhibitors, oxygen glucose deprivation (OGD) conditions were applied for 4 h to simulate transient cerebral ischemia. Apoptotic phenotypes were assessed via lactate dehydrogenase (LDH) assay, MTT cell metabolism assay, and fluorescence-activated cell sorting (FACS). The effect of miR overexpression and inhibition was evaluated by protein and mRNA detection of bcl-2 and caspase-3, critical apoptosis factors. Finally, the direct relationship of miR-129 and bcl-2 and miR-384-5p and caspase-3 was measured by luciferase reporter assay. The overexpression of miR-384-5p and miR-129 deficiency significantly enhanced cell viability, reduced LDH release, and inhibited apoptosis. By contrast, overexpression of miR-129 and miR-384-5p deficiency aggravated hypoxia-induced apoptosis and cell injury. miR-129 overexpression significantly reduced mRNA and protein levels of bcl-2 and miR-129 inhibition significantly increased mRNA and protein levels of bcl-2 in hypoxic cells.miR-384-5p overexpression significantly reduced protein levels of caspase-3 while miR-384-5p deficiency significantly increased protein levels of caspase-3. However, no changes were observed in caspase-3 mRNA in either transfection paradigm. Finally, luciferase reporter assay confirmed caspase-3 to be a direct target of miR-384-5p; however, no binding activity was detected between bcl-2 and miR-129.Transient cerebral ischemia induces differential expression of miR-129 and miR-384-5p which influences apoptosis by regulating apoptotic factors caspase-3 and bcl-2, thereby participating in the pathological mechanism of cerebral ischemia, and becoming potential targets for the treatment of ischemic cerebral injury in the future.

Comparative study of Janus B2XY (X, Y = S, Se, Te) and F-BNBN-H monolayers for water splitting: revealing the positive and negative roles of the intrinsic dipole.

It is widely recognized that the intrinsic dipole in two-dimensional (2D) photocatalysts promotes hydrogen production during water splitting. Herein, we wonder whether the intrinsic dipole plays a negative role in water splitting. In this work, we make a comparative study of the structural, electronic, and photocatalytic properties of Janus B2XY (X, Y = S, Se, Te) and F-BNBN-H monolayers using first principles. Our theoretical results reveal that both B2XY and F-BNBN-H monolayers exhibit spatially separated conduction band minimum (CBM) and valence band maximum (VBM), as well as vacuum level differences at the opposite surfaces due to the intrinsic dipole. The F-BNBN-H monolayer has excellent redox ability for water splitting, because its CBM is located at the surface with a lower vacuum level and its VBM is distributed on the opposite surface possessing a higher vacuum level. By sharp contrast, B2XY monolayers have limited or vanishing redox ability, because their CBM is located at the surface with a higher vacuum level and their VBM is distributed on the opposite surface with a lower vacuum level. This work emphasizes the negative role of vacuum level differences of photocatalysts caused by the intrinsic dipole in water splitting.

Breakfast consumption frequency is associated with dyslipidemia: a retrospective cohort study of a working population.

BACKGROUND: Dyslipidemia is a significant contributor to cardiovascular and cerebrovascular diseases. Research on the relationship between breakfast consumption frequency and dyslipidemia in the working population is lacking. Therefore, we aimed to investigate this relationship based on a retrospective cohort study of a large working population in China. METHODS: This retrospective cohort study used data from the physical examinations and questionnaire survey of working participants at Nanfang Hospital from January 20, 2015 to October 16, 2020. Univariate and multivariate analyses were conducted to explore the relationship between breakfast consumption frequency and dyslipidemia in this working population (n = 7644). RESULTS: The prevalence of dyslipidemia among the participants was 26.4%. The univariate logistic regression test showed that the breakfast consumption frequency was inversely correlated with dyslipidemia. After adjusting for multiple factors, such as sex, age, body mass index, hypertension, hyperuricaemia, diabetes, smoking status, alcohol consumption, education level, marital status, long-term exposure to kitchen oil fumes, attending business dinners, and sleep time, it was found that breakfast consumption remained inversely associated with dyslipidaemia. The odds ratio for daily breakfast consumption was 0.466 (95% confidence interval 0.283-0.770, P = 0.003). After adjusting for confounding factors, we found that the higher the frequency of breakfast consumption, the lower the odds ratios for hypertriglyceridaemia. CONCLUSIONS: This study demonstrated that breakfast consumption frequency was inversely correlated with dyslipidemia. The higher the frequency of breakfast, the lower the risk of hypertriglyceridaemia. This study provides a basis on which dietary suggestions for the working population and lifestyle guidance for patients with a clinical need to prevent dyslipidemia can be made.

[Relevant thoughts on development of traditional Chinese medicine industry in new era].

Since the 18th National Congress of the Communist Party of China(CPC), the CPC and the government have highligh-ted the development of traditional Chinese Medicine(TCM) and issued a series of policies, such as the Plan for Protection and Deve-lopment of Chinese Medicinal Materials(2015-2020) forwarded by the General Office of the State Council in 2015, the Plan for Healthy Development of Traditional Chinese Medicine(2015-2020) released by the General Office of the State Council in the same year, the Healthy China 2030 Plan published by the CPC Central Committee and the State Council in 2016, the Law of the People's Republic of China on Traditional Chinese Medicine which took effect on July 2017, On the Preservation and Innovative Development of Traditional Chinese Medicine promulgated by CPC Central Committee and the State Council in 2019, and Plan for the Development of Traditional Chinese Medicine during the 14th Five-Year Plan Period of China released by the General Office of the State Council in March 2022, to promote the development of the TCM industry, which have brought historical opportunities to the TCM industry. However, TCM industry faces various challenges in the development. In terms of drug development in TCM, the current studies mainly focused on the chemical research and technical requests, which neglected TCM characteristics and cased in conformity between new drug transformation of TCM and clinical practice. Therefore, a more considerable and profound authoritative guideline is needed, and innovative thought and research are necessary for academics and the industry. Through the investigation of the development TCM industry in recent years, this study summarized the policies on and trends of Chinese medicinal materials, new drug development in TCM, catalogue of national basic drugs, and national basic health insurance, and proposed suggestions for further development of TCM industry.

Diterpenoids and Flavonoids from the Twigs of Cephalotaxus fortunei var. alpina.

Three new diterpenoids (a cephalotane, an abietane and a 9(10→20)-abeo-abietane) and one new flavonoid, together with 11 known compounds, were isolated from the twigs of Cephalotaxus fortunei var. alpina. The new compounds were identified by comprehensive spectroscopic (including 1D and 2D-NMR and HR-ESI-MS) analysis. Anti-inflammatory, immunosuppressive and cytotoxic activities of three new compounds were evaluated. 3ß,20-epoxyabieta-8,11,13-triene-3α,12-diol showed weak cytotoxicity against tumor cell lines NCI-H1975, HepG2, MCF-7, while fortalpinoid R and 3-acetonyl-3,5,7,4'-tetrahydroxy-2-methoxyflavanone were not active at 80 µM. None of these compounds showed anti-inflammatory and immunosuppressive activities.

P57-mediated autophagy promotes the efficacy of EGFR inhibitors in hepatocellular carcinoma.

BACKGROUND & AIMS: Resistance to EGFR-targeted therapy is a major obstacle in hepatocellular carcinoma (HCC) treatment, but its underlying mechanism remains unclear. Autophagy plays a vital role in antitumour treatment. Our previous study suggested that p57 is associated with autophagy and cisplatin resistance. The present study aimed to investigate whether p57 can enhance the sensitivity of HCC cells to Erlotinib (Er)/Cetuximab(C-225) and further explore the potential mechanisms of Er/C-225 resistance. METHODS: HCC cells were transfected with pIRES2-EGFP-p57 and pIRES2-EGFP-nc, accompanied by Er/C-225 treatment. Cell viability was detected by an Annexin apoptosis kit and MTT assay. Xenograft experiments were performed to study the function of p57 in the treatment of Er/C-225 in vivo. The level of autophagy was determined by analysis of the appearance of autophagic vacuoles. Western blotting was used to investigate the potential pathways involved. RESULTS: Up-regulation of p57 decreased the level of Er/C-225-induced autophagy and enhanced the decrease in Er/C-225-induced cell viability. P57 overexpression combined with CQ treatment further enhanced the therapeutic efficiency of Er/C-225. The xenograft experiment verified that p57 up-regulation sensitizes HCC cells to Er/C-225. Moreover, a mechanistic investigation demonstrated that the up-regulation of p57 resulted in a decrease of LC3B-II and beclin-1, and an increase in p-PI3K, p-AKT and p-mTOR protein expressions. CONCLUSIONS: Through activating the PI3K/AKT/mTOR signalling pathway, p57 can reverse Er/C-225-induced autophagy, and thereby increase the therapeutic efficiency of Er/C-225 treatment. Given these results, p57 up-regulation may be applicable as a therapeutic strategy to improve EGFR-targeted therapy in HCC.

[Different Types of Low-frequency Electromagnetic Fields Resist Bone Loss Caused by Weightlessness].

Objective To compare the effects of 50-Hz 0.6-mT low-frequency pulsed electromagnetic fields(PEMFs) and 50-Hz 1.8-mT sinusoidal alternating electromagnetic fields(SEMFs) in preventing bone loss in tail-suspended rats,with an attempt to improve the prevention and treatment of bone loss caused by weightlessness.Methods Tail-suspension rat models were used to simulate microgravity on the ground. Forty rats were randomly divided into four groups[control group,hindlimb-suspended(HLS) group,HLS+PEMFs group,and HLS+SEMFs group],with 10 rats in each group. In the PEMFs treatment group and SEMFs treatment group,the intervention was 90 min per day. Rats were sacrificed after four weeks. Bone mineral density(BMD) of femur and vertebra was measured by dual-energy X-ray absorptiometry and biomechanical strength by AG-IS biomechanical instrument. Serum osteocalcin(OC),tartrate-resistant acid phosphatase 5b(Tracp 5b),parathyroid hormone(PTH),and cyclic adenosine monophosphate(cAMP) were detected by ELISA. The microstructure of bone tissue was observed by Micro-CT and HE staining.Results The BMD of the femur(P=0.000) and vertebrae(P=0.001) in the HLS group was significantly lower than in the control group;the BMD of the femurs(P=0.001) and vertebrae(P=0.039) in the HLS+PEMFs group was significantly higher than in the HLS group;the BMD of the femurs in the HLS+SEMFs group was significantly higher than in the HLS group(P=0.003),but the BMD of the vertebrae showed no significant difference(P=0.130). There was no significant difference in the BMD of the femur(P=0.818) and vertebrae(P=0.614) between the HLS+PEMFs group and the HLS+SEMFs group. The maximum load(P=0.000,P=0.009) and elastic modulus(P=0.015,P=0.009) of the femurs and vertebrae in the HLS group were significantly lower than those in the control group;the maximum load of the femur(P=0.038) and vertebrae(P=0.087) in the HLS+PEMFs group was significantly higher than that in the HLS group,but the elastic modulus was not significantly different from that in the HLS group(P=0.324,P=0.091). The maximum load(P=0.190,P=0.222) and elastic modulus(P=0.512,P=0.437) of femurs and vertebrae in the HLS+SEMFs group were not significantly different from those in the HLS group. There were no significant differences in the maximum load and elastic modulus of femurs(P=0.585,P=0.948) and vertebrae(P=0.668,P=0.349) between the HLS+PEMFs group and the HLS+SEMFs group. The serum OC level in the HLS group was significantly lower than that in the control group(P=0.000),and the OC level in HLS+PEMFs group(P=0.000) and HLS+SEMFs group(P=0.006) were significantly higher than that in the HLS group. The serum Tracp 5b concentration in the HLS group was significantly higher than that in the control group(P=0.011). There was no significant difference between the HLS+PEMFs group(P=0.459) and the HLS+SEMFs group(P=0.469) compared with the control group.Serum Tracp 5b concentrations in the HLS+PEMFs group(P=0.056) and the HLS+SEMFs group(P=0.054) were not significantly different from those in the HLS group. The PTH(P=0.000) and cAMP concentrations(P=0.000) in the HLS group were significantly lower than those in the control group. The PTH(P=0.000,P=0.000) and cAMP concentrations(P=0.000,P=0.000) in the HLS+PEMFs group and the HLS+SEMFs group were significantly higher than in the HLS group. The femoral cancellous bone of the HLS group was very sparse and small compared with the control group. The density and volume of the cancellous bone were similar among the control group,HLS+PEMFs group,and HLS+SEMFs group. Compared with the control group,the HLS group had lower BMD(P=0.000),bone volume (BV)/tissue volume(TV)(P=0.000),number of trabecular bone (Tb.N)(P=0.000),and trabecular thickness(Tb.Th)(P=0.000) and higher trabecular bone dispersion(Tb.Sp)(P=0.000) and bone surface area(BS)/BV(P=0.000). Compared with the HLS group,the HLS+PEMFs group and the HLS+SEMFs group had significantly lower Tb.Sp(P=0.000,P=0.000) and BS/BV(P=0.000,P=0.000) and significantly increased BMD(P=0.000,P=0.000),BV/TV(P=0.001,P=0.004),Tb.Th(P=0.000,P=0.001),and Tb.N(P=0.000,P=0.001). The trabecular thickness significantly differed between the HLS+PEMFs group and the HLS+SEMFs group(P=0.024). The HLS group(P=0.000),HLS+PEMFs group(P=0.000),and HLS+SEMFs group(P=0.000) had the significantly lower osteoblast density on the trabecular bone surface than the control group;however,it was significantly higher in the HLS+SEMFs group(P=0.000) and the HLS+PEMFs group(P=0.000) than in the HLS group. The HLS group had significantly lower density of osteoblasts in the endothelium than the control group(P=0.000);however,the density of osteoblasts was significantly higher in HLS+PEMFs group(P=0.000) and HLS+SEMFs group(P=0.000) than HLS group and was significantly higher in HLS+PEMFs group than in HLS+SEMFs group(P=0.041). Compared with the control group,a large number of fatty cavities were produced in the bone marrow cavity in the HLS group,but the fat globules remarkably decreased in the treatment groups,showing no significant difference from the control group. The number of adipose cells per mm 2 bone marrow in the HLS group was 4 times that of the control group(P=0.000);it was significantly smaller in the HLS+PEMFs group(P=0.000) and HLS+SEMFs group(P=0.000) than in the HLS group,whereas the difference between the HLS+PEMFs group and the HLS+SEMFs group was not statistically significant(P=0.086). Conclusions 50-Hz 0.6-mT PEMFs and 50-Hz 1.8-mT SEMFs can effectively increase bone mineral density and biomechanical values in tail-suspended rats,increase the concentration of bone formation markers in rat blood,activate the cAMP pathway by affecting PTH levels,and thus further increase the content of osteoblasts to prevent the deterioration of bone micro-structure. In particular,PEMFs can prevent the reduction of bone mineral density and maximum load value by about 50% and increase the bone mass of tail-suspended rats by promoting bone formation.

LncRNA NKILA upregulation mediates oxygen glucose deprivation/re-oxygenation-induced neuronal cell death by inhibiting NF-κB signaling.

Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) induces severe injury to neuronal cells. The expression and potential function of NKILA (NF-κB Interacting LncRNA) in OGDR-treated neuronal cells were tested in this study. We show that OGDR induced NKILA upregulation to in-activate NF-κB signaling in SH-SY5Y cells and primary murine hippocampal neurons. Conversely, shRNA-mediated NKILA silencing almost reversed OGDR-induced NF-κB inhibition. OGDR-induced neuronal cell viability reduction, apoptosis and necrosis were largely attenuated by NKILA shRNA as well. Conversely, ectopic overexpression of NKILA by a lentiviral vector enhanced OGDR-induced SH-SY5Y cell death. For the mechanism study, we show that OGDR downregulated miR-103 and miR-107 to induce NKILA upregulation in neuronal cells. Transfection of miR-103 mimic or miR-107 mimic almost reversed OGDR-induced NKILA upregulation, NF-κB in-activation and SH-SY5Y cell death. Taken together, OGDR induces NKILA upregulation to in-activate NF-κB signaling, which mediates subsequent neuronal cell death. NKILA could be a novel therapeutic target of ischemic neuronal injury.

Pulsed electromagnetic fields prevented the decrease of bone formation in hindlimb-suspended rats by activating sAC/cAMP/PKA/CREB signaling pathway.

Microgravity is one of the main threats to the health of astronauts. Pulsed electromagnetic fields (PEMFs) have been considered as one of the potential countermeasures for bone loss induced by space flight. However, the optimal therapeutic parameters of PEMFs have not been obtained and the action mechanism is still largely unknown. In this study, a set of optimal therapeutic parameters for PEMFs (50 Hz, 0.6 mT 50% duty cycle and 90 min/day) selected based on high-throughput screening with cultured osteoblasts was used to prevent bone loss in rats induced by hindlimb suspension, a commonly accepted animal model to simulate the space environment. It was found that hindlimb suspension for 4 weeks led to significant decreases in femoral and vertebral bone mineral density (BMD) and their maximal loads, severe deterioration in bone micro-structure, and decreases in levels of bone formation markers and increases in bone resorption markers. PEMF treatment prevented about 50% of the decreased BMD and maximal loads, preserved the microstructure of cancellous bone and thickness of cortical bone, and inhibited decreases in bone formation markers. Histological analyses revealed that PEMFs significantly alleviated the reduction in osteoblast number and inhibited the increase in adipocyte number in the bone marrow. PEMFs also blocked decreases in serum levels of parathyroid hormone and its downstream signal molecule cAMP, and maintained the phosphorylation levels of protein kinase A (PKA) and cAMP response element-binding protein (CREB). The expression level of soluble adenylyl cyclases (sAC) was also maintained. It therefore can be concluded that PEMFs partially prevented the bone loss induced by weightless environment by maintaining bone formation through signaling of the sAC/cAMP/PKA/CREB pathway. Bioelectromagnetics. 39:569-584, 2018. © 2018 Wiley Periodicals, Inc.

[Effect of Compound Medicine of Tanshinone 2A and Resveratrol on Peak Bone Mass in Growing Rats].

Objective To study the effect of the compound medicine of tanshinone 2A and resveratrol on peak bone mass in growing rats and to explore its possible mechanism,so as to explore anti-osteoporosis mechanisms of new traditional Chinese medicine (TCM) drugs. Methods Totally 40 1-month-old female Wistar rats were randomly divided into tanshinone 2A group,resveratrol group,compound group (tanshinone 2A and resveratrol),and normal control group,with 10 rats in each group. Body weight was measured once every two weeks,and the whole body bone mineral density was measured with dual-energy X-ray monthly. When the whole-body bone mineral density became statistically significant between medication groups and control group,all animals were sacrificed to determine the bone mineral density of vertebrae and right femoral bone. The biomechanical properties of femur and vertebrae were measured by AGS-X series universal test,then the bone morphology was analyzed with Fuchsin picric acid staining. Finally,the levels of tartrate-resistant acid phosphatase 5b and osteocalcin were measured with enzyme-linked immunosorbent assay.Results The body weights were not statistically significant among all groups (P>0.05). The whole-body bone mineral density showed no significant difference (P>0.05) after feeding for 1 month;however,two months later,it was significantly different between medication groups and control group;in particular,the whole-body (P=0.016),femoral (P=0.001),and vertebral bone mineral density (P=0.034),bone trabecular number (P=0.024),thickness (P=0.040),and area (P=0.038) were significantly increased in the compound group,along with the significantly decreased trabecular separation degree (P=0.032). Compared with the control group,the compound group had significantly increased osteocalcin (P=0.033) and tartrate-resistant acid phosphatase 5b (P=0.028) levels in serum.Conclusion The compound of tanshinone 2 A and resveratrol can improve the bone density and bone quality in rats,and such effect is higher than either tanshinone 2 A monomer or resveratrolmonomer.

[Effect of Xianling Gubao capsule on bone metabolism in ovariectomized rats].

To investigate the effect of Xianling Gubao capsule in preventing postmenopausal osteoporosis, forty-eight female Wistar rats were randomly divided into four groups: sham group (Sham), ovariectomized group (OVX), ethinylestradiol group (EE) and Xianling Gubao capsule group (XLGB). Rats in each group received ovariectomy, except for sham group. The XLGB group received Xianling Gubao capsule at the dose of 378 mg·kg⁻¹·d⁻¹. The dosage of EE group was 200 µg·kg⁻¹·d⁻¹, and OVX and Sham groups were only fed with equal volume of distilled water. All of the rats were put to death two months later. Bone mineral density, bone biomechanics, bone histomorphometry Micro-CT scanning and organ index of vital organs were calculated and pathologically observed. There was no significant difference in the body weight of rats and organ indexes of lung, kidney, heart and spleen in the experimental groups. There was also no significant change in their pathological observation, but the uterine index of OVX group and XLGB group was significantly lower than that of Sham group. According to the results of BMD test, compared with the OVX group, femurs and vertebrae BMD of the other three groups were increased, with statistically significant differences. On the basis of the results of bone biomechanical test, compared with OVX group, the maximum load values of femur and vertebrae of the other three groups were increased, with statistically significant differences, while the change of elastic modulus was not statistically significant. According to the bone histomorphometry results of VG staining, compared with Sham group, the number of trabecular bone was significantly lower than that in OVX group. Compared with OVX group, the number of trabecular bone in EE group and XLGB group was increased, but with no significant difference between EE and XLGB groups. The results of serum biochemical indexes showed that compared with Sham group, osteocalcin (OC) decreased, while tartrate resistant acid phosphatase 5b (TRACP 5b) increased in OVX group, with statistically significant differences. Compared with OVX group, the OC content of XLGB group and EE group increased, while the content of TRACP 5b decreased, with statistically significant differences. On the basis of the results of Micro-CT scanning, the change trends of femur volume BMD, number of trabecular bone (Tb.N), trabecular bone thickness (Tb.Th), trabecular bone separation (Tb.Sp), bone volume/tissue volume (BV/TV) in the groups were consistent with those of bone histomorphometry. There was no significant change in femoral cortical bone between the two groups. Xianling Gubao capsule can prevent osteoporosis in ovariectomized rats. The possible mechanism is the dual activity of inhibiting bone resorption and improving bone formation.

AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury.

DPSN axons mediate and maintain a variety of normal spinal functions. Unsurprisingly, DPSN tracts have been shown to mediate functional recovery following SCI. KLF7 could contribute to CST axon plasticity after spinal cord injury. In the present study, we assessed whether KLF7 could effectively promote DPSN axon regeneration and synapse formation following SCI. An AAV-KLF7 construct was used to overexpress KLF7. In vitro, KLF7 and target proteins were successfully elevated and axonal outgrowth was enhanced. In vivo, young adult C57BL/6 mice received a T10 contusion followed by an AAV-KLF7 injection at the T7-9 levels above the lesion. Five weeks later, overexpression of KLF7 was expressed in DPSN. KLF7 and KLF7 target genes (NGF, TrkA, GAP43, and P0) were detectably increased in the injured spinal cord. Myelin sparring at the lesion site, DPSN axonal regeneration and synapse formation, muscle weight, motor endplate morphology, and functional parameters were all additionally improved by KLF7 treatment. Our findings suggest that KLF7 promotes DPSN axonal plasticity and the formation of synapses with motor neurons at the caudal spinal cord, leading to improved functional recovery and further supporting the potential of AAV-KLF7 as a therapeutic agent for spinal cord injury.

Evaluation of G3BP1 in the prognosis of acute and acute-on-chronic liver failure after the treatment of artificial liver support system.

BACKGROUND: The increased expression of G3BP1 was positively correlated with the prognosis of liver failure. AIM: To investigate the effect of G3BP1 on the prognosis of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) after the treatment of artificial liver support system (ALSS). METHODS: A total of 244 patients with ALF and ACLF were enrolled in this study. The levels of G3BP1 on admission and at discharge were detected. The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis. RESULTS: This study was shown that lactate dehydrogenase (LDH), alpha-fetoprotein (AFP) and prothrombin time were closely related to the prognosis of patients. After the ALSS treatment, the patient' amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission (difG3BP1) < 0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index. The subgroup analysis showed that the difG3BP1 < 0 group had a higher risk of progression, regardless of model for end-stage liver disease high-risk or low-risk group. At the same time, compared with the inflammatory marks [tumor necrosis factor-α, interleukin (IL)-1ß and IL-18], G3BP1 had higher discrimination and was more stable in the model analysis and validation set. When combined with AFP and LDH, concordance index was respectively 0.84 and 0.8 in training and validation cohorts. CONCLUSION: This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS. The combination of G3BP1, AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.

Stress granules inhibit endoplasmic reticulum stress-mediated apoptosis during hypoxia-induced injury in acute liver failure.

BACKGROUND: Stress granules (SGs) could be formed under different stimulation to inhibit cell injury. AIM: To investigate whether SGs could protect hepatocytes from hypoxia-induced damage during acute liver failure (ALF) by reducing endoplasmic reticulum stress (ERS) mediated apoptosis. METHODS: The agonist of SGs, arsenite (Ars) was used to intervene hypoxia-induced hepatocyte injury cellular model and ALF mice models. Further, the siRNA of activating transcription factor 4 (ATF4) and SGs inhibitor anisomycin was then used to intervene in cell models. RESULTS: With the increase of hypoxia time from 4 h to 12 h, the levels of HIF-1α, ERS and apoptosis gradually increased, and the expression of SGs marker G3BP1 and TIA-1 was increased and then decreased. Compared with the hypoxia cell model group and ALF mice model, the levels of HIF-1α, apoptosis and ERS were increased in the Ars intervention group. After siRNA-ATF4 intervention, the level of SGs in cells increased, and the levels of HIF-1α, ERS and apoptosis decreased. Compared with the siRNA-ATF4 group, the levels of G3BP1 in the siRNA-ATF4+anisomycin group were decreased, and the levels of HIF-1α, ERS and apoptosis were increased. Moreover, compared with the ALF group, the degree of liver injury and liver function, the levels of HIF-1α, ERS and apoptosis in the Ars intervention group were decreased, the level of SGs was increased. CONCLUSION: SGs could protect hepatocytes from hypoxia-induced damage during ALF by reducing ERS-mediated apoptosis.

MicroRNA-21 in gynecological cancers: From molecular pathogenesis to clinical significance.

Ovarian, cervical, and endometrial cancers are the three most common gynecological cancer types (GCs). They hold a significant position as the leading causes of mortality among women with cancer-related death. However, GCs are often diagnosed late, severely limiting the efficacy of current treatment options. Thus, there is an urgent, unmet need for innovative experimentation to enhance the clinical treatment of GC patients. MicroRNAs (miRNAs) are a large and varied class of short noncoding RNAs (22 nucleotides in length) that have been shown to play essential roles in various biological processes involved in development. Recent research has shown that miR-211 influences tumorigenesis and cancer formation, adding to our knowledge of the miR-21 dysregulation in GCs. Furthermore, current research that sheds light on the crucial functions of miR-21 may provide supporting evidence for its potential prognostic, diagnostic, and therapeutic applications in the context of GCs. This review will thus focus on the most recent findings concerning miR-21 expression, miR-21 target genes, and the processes behind GCs. In addition, the latest findings that support miR-21's potential use as a non-invasive biomarker and therapeutic agent for detecting and treating cancer will be elucidated in this review. The roles played by various lncRNA/circRNA-miRNA-mRNA axis in GCs are also comprehensively summarized and described in this study, along with any possible implications for how these regulatory networks may contribute to the pathogenesis of GCs. Also, it is crucial to recognize the complexity of the processes involved in tumour therapeutic resistance as a significant obstacle in treating GCs. Furthermore, this review provides an overview of the current state of knowledge regarding the functional significance miR-21 in therapeutic resistance within the context of GCs.

Chx10+V2a interneurons in spinal motor regulation and spinal cord injury.

Chx10-expressing V2a (Chx10+V2a) spinal interneurons play a large role in the excitatory drive of motoneurons. Chemogenetic ablation studies have demonstrated the essential nature of Chx10+V2a interneurons in the regulation of locomotor initiation, maintenance, alternation, speed, and rhythmicity. The role of Chx10+V2a interneurons in locomotion and autonomic nervous system regulation is thought to be robust, but their precise role in spinal motor regulation and spinal cord injury have not been fully explored. The present paper reviews the origin, characteristics, and functional roles of Chx10+V2a interneurons with an emphasis on their involvement in the pathogenesis of spinal cord injury. The diverse functional properties of these cells have only been substantiated by and are due in large part to their integration in a variety of diverse spinal circuits. Chx10+V2a interneurons play an integral role in conferring locomotion, which integrates various corticospinal, mechanosensory, and interneuron pathways. Moreover, accumulating evidence suggests that Chx10+V2a interneurons also play an important role in rhythmic patterning maintenance, left-right alternation of central pattern generation, and locomotor pattern generation in higher order mammals, likely conferring complex locomotion. Consequently, the latest research has focused on postinjury transplantation and noninvasive stimulation of Chx10+V2a interneurons as a therapeutic strategy, particularly in spinal cord injury. Finally, we review the latest preclinical study advances in laboratory derivation and stimulation/transplantation of these cells as a strategy for the treatment of spinal cord injury. The evidence supports that the Chx10+V2a interneurons act as a new therapeutic target for spinal cord injury. Future optimization strategies should focus on the viability, maturity, and functional integration of Chx10+V2a interneurons transplanted in spinal cord injury foci.

Botryorhodine J, a new anti-MRSA depsidone isolated from endophytic fungus Alternaria alternata Pas11.

A new depsidone derivative botryorhodine J (1), along with six known compounds (2-7) were obtained from solid rice cultures of Alternaria alternata Pas11 that was isolated from leaves of Phragmites australis. The structure of the new compound was elucidated on the basis of combination of NMR spectroscopic data and high resolution mass spectrometry (HRMS). All the isolated compounds were evaluated for their antibacterial activities against a panel of Gram-positive bacterial strains (methicillin-resistant Staphylococcus aureus [MRSA], Bacillus subtilis and S. aureus). Compounds 1 and 6 displayed antibacterial activity against the three bacterial strains with the minimum inhibitory concentration values (MICs) of 14 - 32 µg/mL, while compound 5 showed good antibacterial activity against above bacterial strains with MIC values of 5 - 8 µg/mL.

Synergistic effects of bone mesenchymal stem cells and chondroitinase ABC on nerve regeneration after acellular nerve allograft in rats.

This study aimed to evaluate whether combination therapy of bone marrow stromal cells (BMSCs) transplantation and chondroitinase ABC (ChABC) treatment further enhances axonal regeneration and functional recovery after acellular nerve allograft repair of the sciatic nerve gap in rats. Eight Sprague-Dawley rats were used as nerve donors, and 32 Wistar rats were randomly divided into four groups: Group I: acellular rat sciatic nerve (ARSN) group; Group II: ChABC treatment; Group III: BMSCs transplantation; and Group IV: ChABC treatment and BMSCs transplantation. The results showed that compared with ARSN control group, BMSC transplantation promoted axonal regeneration, the secretion of neural trophic factors NGF, BDNF and axon angiogenesis in nerve graft. ChABC treatment degraded chondroitin sulfate proteoglycans in ARSN in vitro and in vivo and improved BMSCs survival in ARSN. The combination therapy caused much better beneficial effects evidenced by increasing sciatic function index, nerve conduction velocity, restoration rate of tibialis anterior wet muscle weight, and myelinated nerve number, but did not further boost the therapeutic effects on neurotrophic factor production, axon angiogenesis, and sensory functional recovery by BMSC transplantation. Taken together, for the first time, we demonstrate the synergistic effects of BMSC transplantation and BMSCs treatment on peripheral nerve regeneration, and our findings may help establish novel strategies for cell transplantation therapy for peripheral nerve injury.