The mutual interactions among Helicobacter pylori, chronic gastritis, and the gut microbiota: a population-based study in Jinjiang, Fujian

ObjectivesHelicobacter pylori (H. pylori) is a type of bacteria that infects the stomach lining, and it is a major cause of chronic gastritis (CG). H. pylori infection can influence the composition of the gastric microbiota. Additionally, alterations in the gut microbiome have been associated with various health conditions, including gastrointestinal disorders. The dysbiosis in gut microbiota of human is associated with the decreased secretion of gastric acid. Chronic atrophic gastritis (CAG) and H. pylori infection are also causes of reduced gastric acid secretion. However, the specific details of how H. pylori infection and CG, especially for CAG, influence the gut microbiome can vary and are still an area of ongoing investigation. The incidence of CAG and infection rate of H. pylori has obvious regional characteristics, and Fujian Province in China is a high incidence area of CAG as well as H. pylori infection. We aimed to characterize the microbial changes and find potential diagnostic markers associated with infection of H. pylori as well as CG of subjects in Jinjiang City, Fujian Province, China.ParticipantsEnrollment involved sequencing the 16S rRNA gene in fecal samples from 176 cases, adhering to stringent inclusion and exclusion criteria. For our study, we included healthy volunteers (Normal), individuals with chronic non-atrophic gastritis (CNAG), and those with CAG from Fujian, China. The aim was to assess gut microbiome dysbiosis based on various histopathological features. QIIME and LEfSe analyses were performed. There were 176 cases, comprising 126 individuals who tested negative for H. pylori and 50 who tested positive defined by C14 urea breath tests and histopathological findings in biopsies obtained through endoscopy. CAG was also staged by applying OLGIM system.ResultsWhen merging the outcomes from 16S rRNA gene sequencing results, there were no notable variations in alpha diversity among the following groups: Normal, CNAG, and CAG; OLGIM I and OLGIM II; and H. pylori positive [Hp (+)] and H. pylori negative [Hp (–)] groups. Beta diversity among different groups show significant separation through the NMDS diagrams. LEfSe analyses confirmed 2, 3, and 6 bacterial species were in abundance in the Normal, CNAG, and CAG groups; 26 and 2 species in the OLGIM I and OLGIM II group; 22 significant phylotypes were identified in Hp (+) and Hp (–) group, 21 and 1, respectively; 9 bacterial species exhibited significant differences between individuals with CG who were Hp (+) and those who were Hp (–).ConclusionThe study uncovered notable distinctions in the characteristics of gut microbiota among the following groups: Normal, CNAG, and CAG; OLGIM I and OLGIM II; and Hp (+) and Hp (–) groups. Through the analysis of H. pylori infection in CNAG and CAG groups, we found the gut microbiota characteristics of different group show significant difference because of H. pylori infection. Several bacterial genera could potentially serve as diagnostic markers for H. pylori infection and the progression of CG

Critical contributions of protein cargos to the functions of macrophage‑derived extracellular vesicles

Background Macrophages are highly plastic innate immune cells that play key roles in host defense, tissue repair, and homeostasis maintenance. In response to divergent stimuli, macrophages rapidly alter their functions and manifest a wide polarization spectrum with two extremes: M1 or classical activation and M2 or alternative activation. Extracellular vesicles (EVs) secreted from differentially activated macrophages have been shown to have diverse functions, which are primarily attributed to their microRNA cargos. The role of protein cargos in these EVs remains largely unexplored. Therefore, in this study, we focused on the protein cargos in macrophage-derived EVs. Results Naïve murine bone marrow-derived macrophages were treated with lipopolysaccharide or interlukin-4 to induce M1 or M2 macrophages, respectively. The proteins of EVs and their parental macrophages were subjected to quantitative proteomics analyses, followed by bioinformatic analyses. The enriched proteins of M1-EVs were involved in proinflammatory pathways and those of M2-EVs were associated with immunomodulation and tissue remodeling. The signature proteins of EVs shared a limited subset of the proteins of their respective progenitor macrophages, but they covered many of the typical pathways and functions of their parental cells, suggesting their respective M1-like and M2-like phenotypes and functions. Experimental examination validated that protein cargos in M1- or M2-EVs induced M1 or M2 polarization, respectively. More importantly, proteins in M1-EVs promoted viability, proliferation, and activation of T lymphocytes, whereas proteins in M2-EVs potently protected the tight junction structure and barrier integrity of epithelial cells from disruption. Intravenous administration of M2-EVs in colitis mice led to their accumulation in the colon, alleviation of colonic inflammation, promotion of M2 macrophage polarization, and improvement of gut barrier functions. Protein cargos in M2-EVs played a key role in their protective function in colitis. Conclusion This study has yielded a comprehensive unbiased dataset of protein cargos in macrophage-derived EVs, provided a systemic view of their potential functions, and highlighted the important engagement of protein cargos in the pathophysiological functions of these EVs

Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental methods

Natural products are widely used for treating mitochondrial dysfunction-related diseases and cancers. Curcumin, a well-known natural product, can be potentially used to treat cancer. Human salt-induced kinase 3 (SIK3) is one of the target proteins for curcumin. However, the interactions between curcumin and human SIK3 have not yet been investigated in detail. In this study, we studied the binding models for the interactions between curcumin and human SIK3 using computational tools such as homology modeling, molecular docking, molecular dynamics simulations, and binding free energy calculations. The open activity loop conformation of SIK3 with the ketoenol form of curcumin was the optimal binding model. The I72, V80, A93, Y144, A145, and L195 residues played a key role for curcumin binding with human SIK3. The interactions between curcumin and human SIK3 were also investigated using the kinase assay. Moreover, curcumin exhibited an IC50 (half-maximal inhibitory concentration) value of 131 nM, and it showed significant antiproliferative activities of 9.62 ± 0.33 µM and 72.37 ± 0.37 µM against the MCF-7 and MDA-MB-23 cell lines, respectively. This study provides detailed information on the binding of curcumin with human SIK3 and may facilitate the design of novel salt-inducible kinases inhibitors

Scaling Region of Weierstrass-Mandelbrot Function: Improvement Strategies for Fractal Ideality and Signal Simulation

Fractal dimension (D) is widely utilized in various fields to quantify the complexity of signals and other features. However, the fractal nature is limited to a certain scope of concerned scales, i.e., scaling region, even for a theoretically fractal profile generated through the Weierstrass-Mandelbrot (W-M) function. In this study, the scaling characteristics curves of profiles were calculated by using the roughness scaling extraction (RSE) algorithm, and an interception method was proposed to locate the two ends of the scaling region, which were named corner and drop phenomena, respectively. The results indicated that two factors, sampling length and flattening order, in the RSE algorithm could influence the scaling region length significantly. Based on the scaling region interception method and the above findings, the RSE algorithm was optimized to improve the accuracy of the D calculation, and the influence of sampling length was discussed by comparing the lower critical condition of the W-M function. To improve the ideality of fractal curves generated through the W-M function, the strategy of reducing the fundamental frequency was proposed to enlarge the scaling region. Moreover, the strategy of opposite operation was also proposed to improve the consistency of generated curves with actual signals, which could be conducive to practical simulations

Longitudinal changes of oxidative stress and PON1 lactonase activity and status in older pregnant women undergoing assisted reproductive technology: a prospective nested case-control study

Abstract Background Childbearing in women with advanced maternal age (AMA) has increased the need for artificial reproductive technology (ART). ART and oxidative stress are associated with many pregnancy complications. Paraoxonase (PON) 1 is one of the key components responsible for antioxidative activity in high-density lipoprotein (HDL). This study aimed to investigate the longitudinal changes of oxidative stress and PON1 lactonase activity and status in older women undergoing ART. Methods This prospective nested case-control study included 129 control and 64 ART women. Blood samples were obtained respectively at different stages of pregnancy. PON1 level and lactonase activity were assessed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL) as a substrate, respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), homocysteine (HCY), PON1 C-108T and Q192R genetic polymorphisms, and metabolic parameters were analyzed. Results Lactonase activity and level of PON1 gradually decreased with pregnancy progression, while glycolipid metabolism parameters and TAC levels increased with pregnancy progression or significantly raised during the 2nd and 3rd trimesters, and NLA of PON1, TOS, OSI, MDA, and HCY significantly increased before delivery in the ART and control groups. Compared with the control women, the ART women had substantially higher or relatively high lactonase activity and NLA of PON1 and TAC during pregnancy; higher triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, atherogenic index, apolipoprotein (apo) B, and apoB/apoA1 ratio in the 1st trimester; and higher fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, and TG levels before delivery. No significant differences were found in the frequencies of PON1 C-108T and Q192R genotypes and alleles between the ART and control groups. Conclusions Women with AMA undergoing ART had higher TAC, PON1 lactonase activity, and PON1 NLA than control women, suggesting increased compensatory antioxidant capacity in ART women, thus showing higher sensitivity to oxidative stress-related injury and diseases

Roughness Scaling Extraction Accelerated by Dichotomy-Binary Strategy and Its Application to Milling Vibration Signal

Fractal algorithms for signal analysis are developed from geometric fractals and can be used to describe various complex signals in nature. A roughness scaling extraction algorithm with first-order flattening (RSE-f1) was shown in our previous studies to have a high accuracy, strong noise resistance, and a unique capacity to recognize the complexity of non-fractals that are common in signals. In this study, its disadvantage of a long calculation duration was addressed by using a dichotomy-binary strategy. The accelerated RSE-f1 algorithm (A-RSE-f1) retains the three above-mentioned advantages of the original algorithm according to theoretical analysis and artificial signal testing, while its calculation speed is significantly accelerated by 13 fold, which also makes it faster than the typical Higuchi algorithm. Afterwards, the vibration signals of the milling process are analyzed using the A-RSE-f1 algorithm, demonstrating the ability to distinguish different machining statuses (idle, stable, and chatter) effectively. The results of this study demonstrate that the RSE algorithm has been improved to meet the requirements of practical engineering with both a fast speed and a high performance

The Role of Antioxidant Enzymes in the Ovaries

Proper physiological function of the ovaries is very important for the entire female reproductive system and overall health. Reactive oxygen species (ROS) are generated as by-products during ovarian physiological metabolism, and antioxidants are indicated as factors that can maintain the balance between ROS production and clearance. A disturbance in this balance can induce pathological consequences in oocyte maturation, ovulation, fertilization, implantation, and embryo development, which can ultimately influence pregnancy outcomes. However, our understanding of the molecular and cellular mechanisms underlying these physiological and pathological processes is lacking. This article presents up-to-date findings regarding the effects of antioxidants on the ovaries. An abundance of evidence has confirmed the various significant roles of these antioxidants in the ovaries. Some animal models are discussed in this review to demonstrate the harmful consequences that result from mutation or depletion of antioxidant genes or genes related to antioxidant synthesis. Disruption of antioxidant systems may lead to pathological consequences in women. Antioxidant supplementation is indicated as a possible strategy for treating reproductive disease and infertility by controlling oxidative stress (OS). To confirm this, further investigations are required and more antioxidant therapy in humans has to been performed

Scaling Region of Weierstrass-Mandelbrot Function: Improvement Strategies for Fractal Ideality and Signal Simulation

Fractal dimension (D) is widely utilized in various fields to quantify the complexity of signals and other features. However, the fractal nature is limited to a certain scope of concerned scales, i.e., scaling region, even for a theoretically fractal profile generated through the Weierstrass-Mandelbrot (W-M) function. In this study, the scaling characteristics curves of profiles were calculated by using the roughness scaling extraction (RSE) algorithm, and an interception method was proposed to locate the two ends of the scaling region, which were named corner and drop phenomena, respectively. The results indicated that two factors, sampling length and flattening order, in the RSE algorithm could influence the scaling region length significantly. Based on the scaling region interception method and the above findings, the RSE algorithm was optimized to improve the accuracy of the D calculation, and the influence of sampling length was discussed by comparing the lower critical condition of the W-M function. To improve the ideality of fractal curves generated through the W-M function, the strategy of reducing the fundamental frequency was proposed to enlarge the scaling region. Moreover, the strategy of opposite operation was also proposed to improve the consistency of generated curves with actual signals, which could be conducive to practical simulations

Paragenesis and Formation Mechanism of the Dolomite-Mottled Limestone Reservoir of Ordovician Ma4 Member, Ordos Basin

Despite the discovery of high-producing natural gas reservoirs in the low-permeability dolomite-mottled limestone (DML) reservoir of the fourth Member (Ma4) of the Majiagou Formation in the Ordos Basin, the current understanding of the processes responsible for reservoir formation are still superficial, which extremely restricts the effectiveness of deep petroleum exploration and development in the basin. Therefore, this study analyzed the paragenesis process of the DML reservoir through systematic petrographic and geochemical measurements. The DML consists of burrows and matrix. The burrows are mainly filled with dolomite with a small amount of micrite, calcite cement, and solid bitumen. The matrix mainly consists of wakestone or mudstone. The DML has experienced multiple diagenetic events, including seepage-reflux dolomitization, compaction, calcite cement CaI cementation, micrite recrystallization, dissolution, hydrocarbon charging, calcite cement CaII cementation, and dolomite progressive recrystallization. Dolomitization is critical to the DML reservoir formation. The pore created by dolomitization is the hydrocarbon-migrated pathway and storage space. Due to the difference in Mg2+-rich fluid supply, the degree of dolomitization decreases from west to east, which causes the difference in diagenetic evolution of the western and eastern parts of the study area. The high dolomitization degree led to strong anti-compaction ability in the west, contrary to the east. Thus, the reservoir quality of the west is better than the east