Effective separation of maslinic acid and oleanolic acid from olive pomace using high-speed shear off-line coupled with high-speed countercurrent chromatography and their antibacterial activity test.

In this work, a high-speed shear extraction off-line coupling high-speed countercurrent chromatography method was developed to separate maslinic acid and oleanolic acid from olive pomace. To improve extraction efficiency, the polar disparity between maslinic acid and oleanolic acid necessitated the concurrent utilization of both polar and non-polar solvents during high-speed shear extraction. Then, the high-speed shear extraction was directly feed to high-speed countercurrent chromatography for subsequently separation. A total of 250 min were needed to complete the extraction and separation process. This yielded two molecules from 3.3 g of defatted olive pomace: 7.2 mg of 93.8 % pure maslinic acid and 2.3 mg of 90.1 % pure oleanolic acid, both determined by HPLC at 210 nm. Furthermore, the compounds exhibited inhibitory activity against Escherichia coli and Staphylococcus aureus. At a concentration of 100 µg/mL, its efficacy in inhibiting hyaluronidase was comparable to that of the standard drug indomethacin. Compared with the conventional separation method, this coupled technique reduced the whole time due to the direct injection of sample extraction solution. This technique provides a useful approach for the separation of natural products with significant polarity differences.

Aldehyde dehydrogenase 2 gene rs671 G>A polymorphism is associated with an increased risk of digestive tract cancer.

OBJECTIVE: Acetaldehyde can accumulate in cells and form acetaldehyde-DNA adducts that result in digestive tract cancer development. Acetaldehyde dehydrogenase 2 (ALDH2) enzymatic activity is involved in this process. Here, we aimed to analyze the relationship between an ALDH2 gene polymorphism and the digestive tract cancer risk in the Hakka population in China. METHODS: This was a retrospective study, with the ALDH2 rs671 genotype and medical record information collected from all subjects. The relationships between these factors, including various blood cell parameters, and digestive tract cancer susceptibility were analyzed. RESULTS: Overall, 307 cancer patients and 317 controls were included. The cancer patients had significantly higher percentages with a history of smoking and drinking alcohol, as well as an increased platelet to lymphocyte ratio and lower lymphocyte to monocyte ratio, compared with the controls. The ALDH2 rs671 genotype and allele distributions were significantly different between the cancer patients and controls. Logistic regression analysis showed that the ALDH2 G/A genotype (G/A vs. G/G) and A/A genotype (A/A vs. G/G) in the co-dominant mode were risk factors for digestive tract cancer susceptibility. CONCLUSIONS: ALDH2 rs671 G/A or A/A genotype carriers may have an increased risk of developing digestive tract cancers among the Hakka people.

Study on the Effect of Different Endoscopic Auxiliary Treatment of Gastric Mucosal Microtumor.

Objective: To explore the effect of endoscopy in the treatment of gastric mucosal microtumors. Methods: A total of 229 patients with gastric mucosal microtumors were treated in our hospital from January 2016 to December 2021. All patients were divided into three groups group A, group B, and group C. Group A was treated with a transparent cap combined with circle-assisted endoscopic resection, group B with ligator combined with circle-assisted endoscopic resection, and group C with endoscopic mucosal tumor resection. The effects of the three groups were observed. Results: There were 47 patients in group A, 17 males, and 30 females, aged 36-69 years, with an average age of 55.6 ± 9.2 years. There were 54 patients in group B, 18 males, and 36 females, aged 38-72 years, with an average age of 57.6 ± 7.7 years. There were 128 patients in group C, 29 males, and 99 females, aged 33-78 years, with an average age of 55.6 ± 8.4 years. There is no significant difference in age and sex between group A, group B, and group C (P > 0.05). The incidence of postoperative complications in group B (66.7%) was significantly higher than that in group A (57.4%) and group C (53.9%) (all P < 0.05). The incidence of postoperative complications in group A (57.4%) was higher than that in group C (53.9%), and the difference was statistically significant (P < 0.05). Conclusion: Endoscopic mucosal resection and ligation combined with circle-assisted endoscopic resection are effective and safe in the treatment of gastric mucosal microtumors, but it needs to be combined with targeted nursing measures. The transparent cap combined with ring-assisted endoscopic resection has a significant effect on the treatment of gastric mucosal micromasses, reducing operative complications.

Risk factors for rebleeding in patients with obscure gastrointestinal bleeding from southern China.

BACKGROUND: To identify the risk factors associated with rebleeding in obscure gastrointestinal bleeding (OGIB) patients from southern China. METHODS: This retrospective study involved 229 patients who underwent small bowel endoscopy in our hospital between 1 January 2018 and 1 December 2020. The clinical characteristics and risk factors related to rebleeding were retrospectively evaluated. RESULTS: Rebleeding patients were significantly older than non-rebleeding patients (53.0 ± 15.9 vs. 46.2 ± 17.8 years), had lower hemoglobin concentrations (89.2 ± 28.1 vs. 126.2 ± 25.1 g/L), and higher blood urea nitrogen concentrations (5.4 ± 2.6 vs. 4.5 ± 2.2 µmol/L), respectively. A higher percentage of rebleeding patients had diabetes mellitus (13.9% vs. 2.9%) and overt bleeding (70.4% vs. 38.6%), and required blood transfusions (43.1% vs. 8.0%), compared with non-rebleeding patients, respectively. Multivariate logistic analysis indicated that drinking alcohol (odds ratio (OR): 9.27; 95% confidence interval (CI) = 1.35-63.78), anemia (OR: 17.38; 95% CI = 5.48-55.10), and blood transfusion (OR: 3.76; 95% CI = 1.04-13.56) increased the risk of rebleeding in OGIB patients. CONCLUSION: Our data suggested that OGIB patients who drink alcohol, have anemia, and require blood transfusion have an increased risk of rebleeding.

Patients with Gastric Polyps need Colonoscopy Screening at Younger Age: A Large Prospective Cross-Sectional Study in China.

Background To date, it is not clarified whether patients with gastric polyps without any alarming symptoms for colorectal neoplasia need colonoscopy screening. The objective of this study is to prospectively determine the association between gastric polyps and colorectal neoplasia. Methods A multicenter prospective cross-sectional study was performed from July 2012 to December 2014. We compared patients with and without gastric polyps for prevalence of colorectal adenomas. The odds ratios (OR) were computed by logistic regression analysis after multivariable adjustments. Results Totally 1546 patients were included, with 770 patients in the gastric polyp group and 776 in the age- and sex- matched control group. Patients with gastric polyps had greater odds of having any colorectal adenoma (adjusted OR=2.34, 95% confidence interval [CI]: 1.79 to 3.06, p<0.001) and advanced colorectal adenomas (adjusted OR=2.71, 95% CI: 1.74 to 4.23, p<0.001) than those without. The positive association between gastric polyps and colorectal adenomas remained significant in both women (OR=2.34, 95% CI: 1.66 to 3.29, p<0.001) and men (OR=1.87, 95% CI: 1.31 to 2.66, p=0.001). Patients over the age of 40 with gastric polyps had a higher prevalence of colorectal adenomas than those without (40-49yr: OR=1.81, 95% CI=1.02-3.21, p=0.04; 50-59yr: OR=1.88, 95% CI=1.26-2.81, p<0.001; 60-74yr: OR=2.62, 95% CI=1.73-3.98, p<0.001). Conclusions The presence of gastric polyps is significantly associated with a higher prevalence of colorectal adenomas, especially advanced colorectal adenomas. Colonoscopy might be considered in patients with gastric polyps, of any gender, and over the age of 40.

Protein S-Nitrosylation Controls Glycogen Synthase Kinase 3ß Function Independent of Its Phosphorylation State.

RATIONALE: GSK-3ß (glycogen synthase kinase 3ß) is a multifunctional and constitutively active kinase known to regulate a myriad of cellular processes. The primary mechanism to regulate its function is through phosphorylation-dependent inhibition at serine-9 residue. Emerging evidence indicates that there may be alternative mechanisms that control GSK-3ß for certain functions. OBJECTIVES: Here, we sought to understand the role of protein S-nitrosylation (SNO) on the function of GSK-3ß. SNO-dependent modulation of the localization of GSK-3ß and its ability to phosphorylate downstream targets was investigated in vitro, and the network of proteins differentially impacted by phospho- or SNO-dependent GSK-3ß regulation and in vivo SNO modification of key signaling kinases during the development of heart failure was also studied. METHODS AND RESULTS: We found that GSK-3ß undergoes site-specific SNO both in vitro, in HEK293 cells, H9C2 myoblasts, and primary neonatal rat ventricular myocytes, as well as in vivo, in hearts from an animal model of heart failure and sudden cardiac death. S-nitrosylation of GSK-3ß significantly inhibits its kinase activity independent of the canonical phospho-inhibition pathway. S-nitrosylation of GSK-3ß promotes its nuclear translocation and access to novel downstream phosphosubstrates which are enriched for a novel amino acid consensus sequence motif. Quantitative phosphoproteomics pathway analysis reveals that nuclear GSK-3ß plays a central role in cell cycle control, RNA splicing, and DNA damage response. CONCLUSIONS: The results indicate that SNO has a differential effect on the location and activity of GSK-3ß in the cytoplasm versus the nucleus. SNO modification of GSK-3ß occurs in vivo and could contribute to the pathobiology of heart failure and sudden cardiac death.

The current status and future of cardiac stem/progenitor cell therapy for congenital heart defects from diabetic pregnancy.

Pregestational maternal diabetes induces congenital heart defects (CHDs). Cardiac dysfunction after palliative surgical procedures contributes to the high mortality of CHD patients. Autologous or allogeneic stem cell therapies are effective for improving cardiac function in animal models and clinical trials. c-kit+ cardiac progenitor cells (CPCs), the most recognized CPCs, have the following basic properties of stem cells: self-renewal, multicellular clone formation, and differentiation into multiple cardiac lineages. However, there is ongoing debate regarding whether c-kit+ CPCs can give rise to sufficient cardiomyocytes. A new hypothesis to address the beneficial effect of c-kit+ CPCs is that these cells stimulate endogenous cardiac cells through a paracrine function in producing a robust secretome and exosomes. The values of other cardiac CPCs, including Sca1+ CPCs and cardiosphere-derived cells, are beginning to be revealed. These cells may be better choices than c-kit+ CPCs for generating cardiomyocytes. Adult mesenchymal stem cells are considered immune-incompetent and effective for improving cardiac function. Autologous CPC therapy may be limited by the observation that maternal diabetes adversely affects the biological function of embryonic stem cells and CPCs. Future studies should focus on determining the mechanistic action of these cells, identifying new CPC markers, selecting highly effective CPCs, and engineering cell-free products.

The clinical-psychological features of functional dyspepsia patients with weight loss: a multi-center study from China.

AIMS: To investigate the clinical features, appetite, quality of life (QOL), and their associated psychological factors of functional dyspepsia (FD) patients with weight loss. METHODS: For a multicenter study, FD patients were recruited and divided into two groups according to the degree of weight changes during the previous 12 months or less with the onset of dyspepsia symptoms: Group A (≥5%) and Group B (<5%). Patients were evaluated based on the Nepean dyspepsia index (NDI), appetite questionnaire, Hamilton Rating Scale of Anxiety/Depression (HAMA/HAMD). RESULTS: The body mass index in Group A was lower than in Group B, while, the frequency of physician visits in Group A was higher than in Group B. There were no differences in the total scores of NDI-symptom checklist or the items of intensity and bothersomeness between them (p > 0.05), but the frequency item for Group A was significantly higher than Group B (p = 0.035). The incidence of anxiety or depression, the proportion of poor or very poor appetite for Group A was higher than those for Group B (p < 0.05). Subscale scores of the NDI-QOL for Group A were significantly lower than those for Group B (p < 0.05). CONCLUSIONS: FD patients with weight loss have lower BMI, more frequent physician visits, higher psychological disorders, poorer appetite and QoL.

Incidence and psychological-behavioral characteristics of refractory functional dyspepsia: a large, multi-center, prospective investigation from China.

AIM: To explore the incidence and psychological and behavioral characteristics of refractory functional dyspepsia (RFD) in China. METHODS: The subjects of this study were 1341 new outpatients with functional dyspepsia (FD) who were diagnosed according to the Rome III criteria at four hospitals in Guangdong Province between June and September 2012, and 100 healthy volunteers. All subjects completed questionnaires and scales administered. RESULTS: Three-hundred and twenty-seven of the 1341 patients with FD had RFD (24.4%). Patients with RFD had a longer disease duration and a more severe form of the disease than patients with non-refractory FD (NRFD). The prevalence of depression and anxiety symptoms was higher in patients with RFD than in patients with NRFD. The prevalence of unhealthy eating behaviors, lack of physical activity, and sleeping disorders was higher in patients with RFD than in patients with NRFD. Patients with RFD sought medical advice on more occasions and spent more money on treatment than patients with NRFD. Finally, patients with RFD had poorer quality of life than patients with NRFD. CONCLUSION: RFD is not rare in clinical practice and should get attention by patients and doctors because of its long duration, severe symptoms, and associations with abnormal psychology and poor quality of life.

Incidence and clinical features of hyperlipidemic acute pancreatitis from Guangdong, China: a retrospective multicenter study.

OBJECTIVE: This study aimed to investigate the clinical features and incidence trends of hyperlipidemic acute pancreatitis (HLAP) of multicenter studies in Guangdong, China, for 15 years. METHODS: The medical records of 1582 patients with acute pancreatitis who were admitted to 4 general hospitals of Guangdong from January 1990 to December 2005 were reviewed. The inpatient medical and radiologic records were reviewed to determine clinical features, severity, complications, mortality, and recurrence rate. RESULTS: A total of 7.8% (123/1582) patients met the HLAP criteria. Incidence of HLAP was approximately 2.6 times increased during 15 years (3.4% in 1990-1994, 5.9% in 1995-1999, and 8.9% in 2000-2005, respectively) and ranged from 3.3% to 15.5% in 4 hospitals across Guangdong. A history of diabetes was present in 31.7% and alcohol use in 18.7%. The mean (SD) triglyceride levels were 13.6 (7.2) mmol/L. Amylase was elevated higher than normal in 81.2% but only 2 times normal in 17.1% and 3 times normal in 37.6%. The frequency of severe acute pancreatitis, organ dysfunction, rate of recurrence, and mortality of HLAP was significantly higher than biliary-induced pancreatitis. CONCLUSIONS: The incidence of HLAP had significantly increased during the past 15 years with a clear geographic variation and remarkable severity and recurrent trend.

Cysteine oxidative posttranslational modifications: emerging regulation in the cardiovascular system.

In the cardiovascular system, changes in oxidative balance can affect many aspects of cellular physiology through redox-signaling. Depending on the magnitude, fluctuations in the cell's production of reactive oxygen and nitrogen species can regulate normal metabolic processes, activate protective mechanisms, or be cytotoxic. Reactive oxygen and nitrogen species can have many effects including the posttranslational modification of proteins at critical cysteine thiols. A subset can act as redox-switches, which elicit functional effects in response to changes in oxidative state. Although the general concepts of redox-signaling have been established, the identity and function of many regulatory switches remains unclear. Characterizing the effects of individual modifications is the key to understand how the cell interprets oxidative signals under physiological and pathological conditions. Here, we review the various cysteine oxidative posttranslational modifications and their ability to function as redox-switches that regulate the cell's response to oxidative stimuli. In addition, we discuss how these modifications have the potential to influence other posttranslational modifications' signaling pathways though cross-talk. Finally, we review the increasing number of tools being developed to identify and quantify the various cysteine oxidative posttranslational modifications and how this will advance our understanding of redox-regulation.

Redox regulation of mitochondrial ATP synthase.

Reversible cysteine oxidative post-translational modifications (Ox-PTMs) represent an important mechanism to regulate protein structure and function. In mitochondria, redox reactions can modulate components of the electron transport chain (ETC), the F(1)F(0)-ATP synthase complex, and other matrix proteins/enzymes. Emerging evidence has linked Ox-PTMs to mitochondrial dysfunction and heart failure, highlighting some potential therapeutic avenues. Ox-PTMs can modify a variety of amino acid residues, including cysteine, and have the potential to modulate the function of a large number of proteins. Among this group, there is a selected subset of amino acid residues that can function as redox switches. These unique sites are proposed to monitor the cell's oxidative balance through their response to the various Ox-PTMs. In this review, the role of Ox-PTMs in the regulation of the F(1)F(0)-ATP synthase complex is discussed in the context of heart failure and its possible clinical treatment.

The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria Streptomyces.

In cells that exhibit apical growth, mechanisms that regulate cell polarity are crucial for determination of cellular shape and for the adaptation of growth to intrinsic and extrinsic cues. Broadly conserved pathways control cell polarity in eukaryotes, but less is known about polarly growing prokaryotes. An evolutionarily ancient form of apical growth is found in the filamentous bacteria Streptomyces, and is directed by a polarisome-like complex involving the essential protein DivIVA. We report here that this bacterial polarization machinery is regulated by a eukaryotic-type Ser/Thr protein kinase, AfsK, which localizes to hyphal tips and phosphorylates DivIVA. During normal growth, AfsK regulates hyphal branching by modulating branch-site selection and some aspect of the underlying polarisome-splitting mechanism that controls branching of Streptomyces hyphae. Further, AfsK is activated by signals generated by the arrest of cell wall synthesis and directly communicates this to the polarisome by hyperphosphorylating DivIVA. Induction of high levels of DivIVA phosphorylation by using a constitutively active mutant AfsK causes disassembly of apical polarisomes, followed by establishment of multiple hyphal branches elsewhere in the cell, revealing a profound impact of this kinase on growth polarity. The function of AfsK is reminiscent of the phoshorylation of polarity proteins and polarisome components by Ser/Thr protein kinases in eukaryotes.

Identification and verification of redox-sensitive proteins in Arabidopsis thaliana.

Environmental stresses often trigger rapid generation of reactive oxygen species (ROS) in plants. Excessive amount of ROS can cause damage to plant cells and thus need to be counteracted by cellular antioxidant systems. On the other hand, ROS also serve as signaling molecules that modulate various physiological responses and developmental processes. Signaling function of ROS is largely achieved through oxidative modifications of redox-sensitive proteins. Therefore, development of methods for high-throughput identification of redox-sensitive proteins and for verifying and characterizing their in vivo redox states is essential for advancing our understanding of ROS-mediated signaling pathways.