Brassinosteroids biosynthetic gene MdBR6OX2 regulates salt stress tolerance in both apple and Arabidopsis.

Salt stress is a critical limiting factor for fruit yield and quality of apples. Brassinosteroids (BRs) play an important role in response to abiotic stresses. In the present study, application of 2,4- Epicastasterone on seedlings of Malus 'M9T337' and Malus domestica 'Gala3' alleviated the physiological effects, such as growth inhibition and leaf yellowing, induced by salt stress. Further analysis revealed that treatment with NaCl induced expression of genes involved in BR biosynthesis in 'M9T337' and 'Gala3'. Among which, the expression of BR biosynthetic gene MdBR6OX2 showed a three-fold upregulation upon salt treatment, suggesting its potential role in response to salt stress in apple. MdBR6OX2, belonging to the CYP450 family, contains a signal peptide region and a P450 domain. Expression patterns analysis showed that the expression of MdBR6OX2 can be significantly induced by different abiotic stresses. Overexpressing MdBR6OX2 enhanced the tolerance of apple callis to salt stress, and the contents of endogenous BR-related compounds, such as Typhastero (TY), Castasterone (CS) and Brassinolide (BL) were significantly increased in transgenic calli compared with that of wild-type. Extopic expression of MdBR6OX2 enhanced tolerance to salt stress in Arabidopsis. Genes associated with salt stress were significantly up-regulated, and the contents of BR-related compounds were significantly elevated under salt stress. Our data revealed that BR-biosynthetic gene MdBR6OX2 positively regulates salt stress tolerance in both apple calli and Arabidopsis.

Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent type of chronic liver disease. However, the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies. Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoetiology and suggest functional therapeutic and diagnostic options. Pyroptosis, ferroptosis, and necroptosis are the main subtypes of non-apoptotic regulated cell deaths (RCDs), each of which represents particular characteristics. Considering the complexity of the findings, the present study aimed to review these types of RCDs and their contribution to NAFLD progression, and subsequently discuss in detail the role of necroptosis in the pathoetiology, diagnosis, and treatment of the disease. The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer, hence it has potential in diagnostic and therapeutic approaches. Nevertheless, further studies are necessary.

[Efficacy of intramuscular injection of Xiyanping injection for the treatment of acute bronchitis in children: a multicenter, randomized, parallel-controlled clinical study]. / å–œç‚Žå¹³æ³¨å°„æ¶²è‚Œå† æ³¨å°„æ²»ç–—å°å„¿æ€¥æ€§æ”¯æ°”ç®¡ç‚Žçš„ç–—æ•ˆï¼šä¸€é¡¹å¤šä¸­å¿ƒã€éšæœºã€å¹³è¡Œå¯¹ç §ä¸´åºŠç ”ç©¶.

OBJECTIVES: To study the efficacy and safety of Xiyanping injection through intramuscular injection for the treatment of acute bronchitis in children. METHODS: A prospective study was conducted from December 2021 to October 2022, including 78 children with acute bronchitis from three hospitals using a multicenter, randomized, parallel-controlled design. The participants were divided into a test group (conventional treatment plus Xiyanping injection; n=36) and a control group (conventional treatment alone; n=37) in a 1:1 ratio. Xiyanping injection was administered at a dose of 0.3 mL/(kg·d) (total daily dose ≤8 mL), twice daily via intramuscular injection, with a treatment duration of ≤4 days and a follow-up period of 7 days. The treatment efficacy and safety were compared between the two groups. RESULTS: The total effective rate on the 3rd day after treatment in the test group was significantly higher than that in the control group (P<0.05), while there was no significant difference in the total effective rate on the 5th day between the two groups (P>0.05). The rates of fever relief, cough relief, and lung rale relief in the test group on the 3rd day after treatment were higher than those in the control group (P<0.05). The cough relief rate on the 5th day after treatment in the test group was higher than that in the control group (P<0.05), while there was no significant difference in the fever relief rate and lung rale relief rate between the two groups (P>0.05). The cough relief time, daily cough relief time, and nocturnal cough relief time in the test group were significantly shorter than those in the control group (P<0.05), while there were no significant differences in the fever duration and lung rale relief time between the two groups (P>0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05). CONCLUSIONS: The overall efficacy of combined routine treatment with intramuscular injection of Xiyanping injection in the treatment of acute bronchitis in children is superior to that of routine treatment alone, without an increase in the incidence of adverse reactions.

Ivermectin inhibits tumor metastasis by regulating the Wnt/ß-catenin/integrin ß1/FAK signaling pathway.

Tumor metastasis is the major cause of cancer mortality; therefore, it is imperative to discover effective therapeutic drugs for anti-metastasis therapy. In the current study, we investigated whether ivermectin (IVM), an FDA-approved antiparasitic drug, could prevent cancer metastasis. Colorectal and breast cancer cell lines and a cancer cell-derived xenograft tumor metastasis model were used to investigate the anti-metastasis effect of IVM. Our results showed that IVM significantly inhibited the motility of cancer cells in vitro and tumor metastasis in vivo. Mechanistically, IVM suppressed the expressions of the migration-related proteins via inhibiting the activation of Wnt/ß-catenin/integrin ß1/FAK and the downstream signaling cascades. Our findings indicated that IVM was capable of suppressing tumor metastasis, which provided the rationale on exploring the potential clinical application of IVM in the prevention and treatment of cancer metastasis.

The role of protein kinase C alpha in tri-ortho-cresyl phosphate-induced autophagy in human neuroblastoma SK-N-SH cells.

As an organophosphorus ester, tri-ortho-cresyl phosphate (TOCP) has been widely used in agriculture and industry. It is reported that TOCP can induce organophosphate-induced delayed neuropathy (OPIDN) in sensitive animal and human species. However, the exact molecular mechanisms underlying TOCP-induced neurotoxicity are still unknown. In this study, we found that TOCP could induce autophagy by activating protein kinase C alpha (PKCα) signaling in neuroblastoma SK-N-SH cells. PKCα activators could positively regulate TOCP-induced autophagy by increasing the expression levels of neighbor BRCA1 gene protein 1 (NBR1), LC3 and P62 autophagic receptor protein. Furthermore, PKCα activation impaired the ubiquitin-proteasome system (UPS), resulting in inhibition of proteasome activity and accumulation of ubiquitinated proteins. UPS dysfunction could stimulate autophagy to serve as a compensatory pathway, which contributed to the accumulation of the abnormally hyperphosphorylated tau proteins and degradation of impaired proteins of the MAP 2 and NF-H families in neurodegenerative disorders.

Comparison of Autocross-Linked Hyaluronic Acid Gel and Intrauterine Device for Preventing Intrauterine Adhesions in Infertile Patients: A Randomized Clinical Trial.

OBJECTIVES: The objective of this study is to evaluate the efficacy of autocross-linked hyaluronic acid (HA) compared with intrauterine device (IUD) for preventing intrauterine adhesions (IUAs) in infertile patients after hysteroscopic adhesiolysis. MATERIALS AND METHODS: A randomized clinical trial (ChiCTR-IOR-16007746). Upon completion of adhesiolysis, 3 ml of HA gel was placed into the uterine cavity in Group A; 3 ml of HA gel and an IUD were placed in Group B; and only an IUD was placed in Group C. A second hysteroscopic examination was performed in all patients at approximately 1 month postoperatively for the evaluation of IUA. The primary outcome measure was the effective rate of IUA prevention based on the American Fertility Society (AFS) scoring system. RESULTS: Eighty-nine women were randomly distributed into two groups for intention to treat with 30 patients in Group A, 24 patients in Group B, and 35 patients in Group C. Patients were scored and stratified into three degrees and were enrolled using the simple random sampling method. The three groups were well balanced. There were no significant differences in age, endometrial thickness, the previous number of pregnancy, and the distribution of adhesion categories across mild, moderate, and severe between the three groups. The effective rate of IUA prevention, the AFS score after therapy, and the percentage improvements of Chinese score and AFS score before and after surgery were statistically significant difference between Groups A and C. The clinical pregnancy rate in Group A was higher than those in Groups B and C, but the difference was not statistically significant. CONCLUSION: HA gel has an advantage over an IUD in reducing IUA recurrence and decreasing adhesions.

Optimal waiting period for fresh embryo transfer after hysteroscopic adhesiolysis: a retrospective cohort study.

BACKGROUND: Very few studies have been conducted regarding the optimal time interval between hysteroscopic adhesiolysis and the embryo transfer (ET). Investigation of this optimal time may be helpful for assisted reproductive technology. Therefore, we investigated effects of the interval between hysteroscopic adhesiolysis and ET upon in vitro fertilization (IVF) cycle outcomes. METHODS: Patients were recruited between January 2014 and September 2017 at the Reproductive Hospital Affiliated to Shandong University. Patients who were diagnosed with intra-uterine adhesion (IUA) and underwent hysteroscopic adhesiolysis before fresh IVF-ET or intra-cytoplasmic sperm injection cycles were classified into three groups according to the interval between hysteroscopic adhesiolysis and ET: less than 90 days (Group 1), 90 to 180 days (Group 2), and greater than 180 days (Group 3). Baseline characteristics, controlled ovarian stimulation (COS) response, and pregnancy outcomes after ET were compared. Analysis of variance or non-parametric tests were used to test numerical data. The Pearson's Chi-squared test was used to test categorical data. RESULTS: A total of 312 patients were recruited as follows: 112 in Group 1, 137 in Group 2, and 63 in Group 3. There were no differences in baseline and COS characteristics among the three groups. The live-birth rate in Group 2 (40.1%) was significantly higher than that in Group 1 (17.9%; χ = 14.545, P < 0.001). There were no significant differences in the rates of biochemical, ongoing, and clinical pregnancy, and biochemical and clinical pregnancy abortion, as well as stillbirth among the groups. In the mild IUA patients, the live-birth rate was significantly higher in Group 2 (42.6%) compared with Group 1 (22%; χ = 8.413, P = 0.004). In the moderate IUA patients, Group 2 (35.7%) had a higher frequency of live births than Group 1 (6.7%; χ = 8.187, P = 0.004). CONCLUSIONS: The optimal waiting period for fresh ET after hysteroscopic adhesiolysis was 90 to 180 days in the current study.

Expanded alleles of the FMR1 gene are related to unexplained recurrent miscarriages.

Up to 50% of recurrent miscarriage cases in women occur without an underlying etiology. In the current prospective case-control study, we determined the impact of CGG trinucleotide expansions of the fragile-X mental retardation 1 (FMR1) gene in 49 women with unexplained recurrent miscarriages. Case group consisted of women with two or more unexplained consecutive miscarriages. Blood samples were obtained and checked for the presence of expanded alleles of the FMR1 gene using PCR. Patients harboring the expanded allele, with a threshold set to 40 repeats, were further evaluated by sequencing. The number of abortions each woman had, was not associated with her respective CGG repeat number (P=0.255). The repeat sizes of CGG expansion in the FMR1 gene were significantly different in the two population groups (P=0.027). All the positive cases involved intermediate zone carriers. Hence, the CGG expanded allele of the FMR1 gene might be associated with unexplained multiple miscarriages; whether such an association is coincidental or causal can be confirmed by future studies using a larger patient cohort.

Serum Pepsinogen Levels Are Correlated With Age, Sex and the Level of Helicobacter pylori Infection in Healthy Individuals.

BACKGROUND: To explore the relationship between age, sex, the level of Helicobacter pylori (HP) infection and serum pepsinogen (PG) in healthy people undergoing a medical examination. METHODS: A total of 6,596 "healthy" individuals undergoing a medical examination were selected as subjects in this study. The concentrations of serum pepsinogen I (PGI) and serum pepsinogen II (PGII) were tested for each of the subjects using time-resolved fluorescence immunoassay characterized with high sensitivity and wide measuring range. The infection ratio and level of HP were tested using a 13C-urea breath test to analyze the relationship between age, sex, HP infection, and serum PGs. RESULTS: The PGI, PGII and PGI-to-PGII ratio (x¯±S) were higher in males than in females. The serum PGI and PGII levels gradually increased with age. HP infection rate was 48.83%, and the serum PGI, PGII and PGI-to-PGII ratio (x¯±S) were 187.05 ± 73.50µg/L, 18.09 ± 8.68µg/L and 11.67 ± 5.44, respectively in the HP-positive group and 150.39 ± 67.04µg/L, 11.50 ± 7.45µg/L and 15.67 ± 8.19, respectively in the HP-negative group. There was significant difference in the detection rate of an abnormal PG between the 2 groups as with the worsening of HP infection, 13C-urea breath test and serum PGI and PGII levels increased, but the PGI-to-PGII ratio decreased significantly. CONCLUSIONS: Serum PGI and PGII levels were correlated with age, sex and the level of HP infection. Therefore, the influencing factors of age, sex and the level of HP infection should be considered when screening stomach diseases using PG.

[Relationship between angiotensin converting enzyme gene polymorphism and essential hypertension in children].

OBJECTIVE: To study the relationship between insertion/deletion (I/D) polymorphism of 287 bp in the 16th intron of angiotensin converting enzyme (ACE) and essential hypertension in children. METHODS: I/D polymorphism of 287 bp in the 16th intron of ACE was detected using PCR in 105 children with essential hypertension and 105 normal children as control group. RESULTS: There was an I/D polymorphism in the 16th intron of ACE in the hypertension and the control groups: type II, type ID and type DD. The genotype frequencies of type DD, type ID and type II in the hypertension group were 30.5%, 47.6% and 21.9%, respectively. The genotype frequencies of type DD, type ID and type II in the control group were 14.3%, 46.7% and 39.1%, respectively. There were significant differences in the genotype frequencies of types DD and II between the two groups (P<0.01). The allele frequency of type D (54.3% vs 37.6%) was significantly higher in the hypertension group; in contrast, the allele frequency of type I (45.7% vs 62.4%) was significantly lower than in the control group (P<0.01). CONCLUSIONS: Polymorphism of type II, type ID and type DD exits in ACE. The deletion of 287 bp in the 16th intron of ACE might be associated with the occurrence of essential hypertension in children.

Therapeutic efficacy of high-dose vitamin C on acute pancreatitis and its potential mechanisms.

AIM: To observe the therapeutic efficacy of high-dose Vitamin C (Vit. C) on acute pancreatitis (AP), and to explore its potential mechanisms. METHODS: Eighty-four AP patients were divided into treatment group and control group, 40 healthy subjects were taken as a normal group. In the treatment group, Vit. C (10 g/day) was given intravenously for 5 days, whereas in the control group, Vit. C (1 g/day) was given intravenously for 5 days. Symptoms, physical signs, duration of hospitalization, complications and mortality rate were monitored. Meanwhile, serum amylase, urine amylase and leukocyte counts were also determined. The concentration of plasma vitamin C (P-VC), plasma lipid peroxide (P-LPO), plasma vitamin E (P-VE), plasma beta-carotene (P-beta-CAR), whole blood glutathione (WB-GSH) and the activity of erythrocyte surperoxide dimutase (E-SOD) and erythrocyte catalase (E-CAT) as well as T lymphocyte phenotype were measured by spectrophotometry in the normal group and before and after treatment with Vit. C in the treatment and the control group. RESULTS: Compared with the normal group, the average values of P-VC, P-VE, P-beta-CAR, WB-GSH and the activity of E-SOD and E-CAT in AP patients were significantly decreased and the average value of P-LPO was significantly increased, especially in severe acute pancreatitis (SAP) patients (P<0.05. P-VC, P=0.045; P-VE, P=0.038; P=0.041; P-beta-CAR, P=0.046; WB-GSH, P=0.039; E-SOD, P=0.019; E-CAT, P=0.020; P-LPO, P=0.038). Compared with the normal group, CD3 and CD4 positive cells in AP patients were significantly decreased. The ratio of CD4/CD8 and CD4 positive cells were decreased, especially in SAP patients (P<0.05. CD4/CD8, P=0.041; CD4, P =0.019). Fever and vomiting disappeared, and leukocyte counts and amylase in urine and blood become normal quicker in the treatment group than in the control group. Moreover, patients in treatment group also had a higher cure rate, a lower complication rate and a shorter in-ward days compared with those in he control group. After treatment, the average value of P-VC was significantly higher and the values of SIL-2R, TNF-alpha, IL-6 and IL-8 were significantly lower in the treatment group than in the control group (P<0.05 P-VC, P=0.045; SIL-2R, P=0.012; TNF-alpha, P=0.030; IL-6, P=0.015; and IL-8, P=0.043). In addition, the ratio of CD4/CD8 and CD4 positive cells in the patients of treatment group were significantly higher than that of the control group after treatment (P<0.05. CD4/CD8, P=0.039; CD4, P=0.024). CONCLUSION: High-dose vitamin C has therapeutic efficacy on acute pancreatitis. The potential mechanisms include promotion of anti-oxidizing ability of AP patients, blocking of lipid peroxidation in the plasma and improvement of cellular immune function.