Helicobacter pylori infection, a worldwide health issue, is typically treated with standard antibiotic therapies. However, these treatments often face resistance and non-compliance due to side ...effects. In this umbrella review, we aimed to comprehensively assess the impact of probiotics supplementation in different preparations on Helicobacter pylori standard treatment. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials in the Cochrane Library from inception to June 1, 2023, to identify systematic reviews with meta-analyses that focused on eradication rates, total side effects and other outcomes of interest. The most comprehensive meta-analysis was selected for data extraction. AMSTAR 2 was used to assess quality of meta-analyses. Overall, 28 unique meta-analyses based on 534 RCTs were included. The results suggests that probiotics supplementation with pooled probiotic strains was significantly associated with improved eradication rates (RR 1.10, 95% CI 1.06-1.14) and reduced risk of total side effects (RR 0.54, 95% CI 0.42-0.70) compared with standard therapy alone. Single-strained or multi-strained preparation of probiotics supplementation showed similar results. Despite Bifidobacterium spp. showing the highest potential for eradication, the study quality was critically low for most meta-analyses, necessitating further high-quality research to explore the optimal probiotic strains or their combinations for Helicobacter pylori treatment.aq_start?>Kindly check and confirm the edit made in article title.
Maternally inherited diabetes and deafness is a rare genetic disease mainly caused by a point mutation in mitochondrial deoxyribonucleic acid. Lipoprotein lipase gene mutations are associated with ...familial dyslipidemias, which are difficult to manage. We reported for the first time a case that had both maternally inherited diabetes and severe hyperlipidemia caused by lipoprotein lipase gene mutation (C.347(exon3)G>C) that was resistant to fenofibrate and atorvastatin. We were able to manage the patient’s hyperlipidemia with bezafibrate, and her diabetes was well controlled with insulin. In conclusion, genetic testing is helpful in identifying rare and interesting cases when clinicians suspect inheritable diseases. Additionally, when one fibrate drug is ineffective in treating hyperlipidemia, it might be worthwhile trying another fibrate.
The pedigree chart of the patient’s family. The arrow denotes proband (the patient) who has a point mutation in the lipoprotein lipase gene (heterozygous, C.347(exon3)G>C) and a point mutation in mitochondrial deoxyribonucleic acid (tRNA3243A>G).
Protein tyrosine phosphatase 1B (PTP1B) is a key element in the negative regulation of the insulin signaling pathway and may play an important role in diabetes and obesity. We identified ursolic ...acid, a natural pentacyclic triterpenoid that occurs widely in traditional Chinese medicinal herbs, as an inhibitor of PTP1B by screening an extract library of the traditional Chinese medicinal herbs used a diabetes clinic. By modifying urosolic acid, we designed and synthesized a derivative with a
K
i of 283 nM. As competitive inhibitors of PTP1B, ursolic acid and its derivative also inhibit T-cell protein tyrosine phosphatase and src homology phosphatase-2 but not leucocyte antigen-related phosphatase or protein tyrosine phosphatase α and ε, which are all possibly involved in the insulin pathway. The ursolic acid derivative enhanced insulin receptor phosphorylation in CHO/
hIR cells and stimulate glucose uptake in L6 myotubes.
We report a high-throughput assay for H2S-producing enzymes, which is based on a newly designed tandem-well plate. Screening of 21,599 agents identified several potent inhibitors of cystathionine ...β-synthase and cystathionine γ-lyase, the two key enzymes generating H2S in mammals, with IC50 values in the low two-digit micromolar range.
To evaluate the effectiveness of a risk-adapted colorectal cancer screening strategy constructed utilizing genetic and environmental risk score (ERS).
A polygenic risk score (PRS) was constructed ...based on 20 previously published single nucleotide polymorphisms for colorectal cancer in East Asian populations, using 2 160 samples with MassARRAY test results from a multicenter randomized controlled trial of colorectal cancer screening in China. The ERS was calculated using the Asia-Pacific Colorectal Screening Score system. Logistic regression was used to analyze the association between PRS alone and PRS combined with ERS and colorectal neoplasms risk, respectively. We also designed a risk-adapted screening strategy based on PRS and ERS (high-risk participants undergo a single colonoscopy, low-risk participants undergo an annual fecal immunochemical test, and those with positive results undergo further diagnostic colonoscopy) and compared its effectiveness with the all-acceptance colonoscopy strategy.
The high P
Abstract
In this paper, the method of producing bubbles by the reaction of aluminum powder and sodium hydroxide is used to make foam concrete test blocks and test their expansion rate and compressive ...strength. The foamed concrete was made through experiments of controlling the amount of cement, water and the relative content of aluminum powder, and the best mix ratio was selected from the comparative analysis of the compressive strength of 7d, 14d and 28dconcrete. Experimental results: The amount of cement and the water-cement ratio and the relative content of aluminum powder have a significant impact on the compressive strength and expansion rate. Conclusion: Starting from the ratio of the relative content of aluminum powder in foamed concrete to the amount of cement, the analysis of compressive strength and expansion rate provides a theoretical basis for the future study of its mix ratio, which greatly shortens the test time and saves costs.
Cystathionine β-synthase (CBS) is responsible for the first enzymatic reaction in the transsulfuration pathway of sulfur amino acids. The molecular function and mechanism of CBS as well as that of ...transsulfuration pathway remain ill-defined in cell proliferation and death. In the present study, we designed, synthesized and obtained a bioactive inhibitor CH004 for human CBS, which functions in vitro and in vivo. CH004 inhibits CBS activity, elevated the cellular homocysteine and suppressed the production of hydrogen sulfide in a dose-dependent manner in cells or in vivo. Chemical or genetic inhibition of CBS demonstrates that endogenous CBS is closely coupled with cell proliferation and cell cycle. Moreover, CH004 substantially retarded in vivo tumor growth in a xenograft mice model of liver cancer. Importantly, inhibition of CBS triggers ferroptosis in hepatocellular carcinoma. Overall, the study provides several clues for studying the interplays amongst transsulfuration pathway, ferroptosis and liver cancer.
Deprescribing aims to reduce polypharmacy, especially in the elderly population, in order to maintain or improve quality of life, reduce harm from medications, and limit healthcare expenditure. ...Coronavirus disease (COVID-19) is an infectious disease that has led to a pandemic and has changed the lives many throughout the world. The mode of transmission of this virus is from person to person through the transfer of respiratory droplets. Therefore, non-essential healthcare services involving direct patient interactions, including deprescribing, has been on hiatus to reduce spread. Barriers to deprescribing before the pandemic include patient and system related factors, such as resistance to change, patient's knowledge deficit about deprescribing, lack of alternatives for treatment of disease, uncoordinated delivery of health services, prescriber's attitudes and/or experience, limited availability of guidelines for deprescribing, and lack of evidence on preventative therapy. Some of these barriers can be mitigated by using the following interventions:patient education, prioritization of non-pharmacological therapy, incorporation of electronic health record (EHR), continuous prescriber education, and development of research studies on deprescribing. Currently, deprescribing cannot be delivered through in person interactions, so virtual care is a reasonable alternative format. The full incorporation of EHR throughout Canada can add to the success of this strategy. However, there are several challenges of conducting deprescribing virtually in the elderly population. These challenges include, but are not limited, to their inability to use technology, lack of literacy, lack of assistance from others, greater propensity for withdrawal effects, and increased risk of severe consequences, if hospitalized. Virtual care is the future of healthcare and in order to retain the benefits of deprescribing, additional initiatives should be in place to address the challenges that elderly patients may experience in accessing deprescribing virtually. These initiatives should involve teaching elderly patients how to use technology to access health services and with technical support in place to address any concerns.
A novel synthesis of the human leukocyte common antigen-related phosphatase (LAR) inhibitor, illudalic acid, has been achieved by a route more amenable to structure modifications. A preliminary study ...of the structure–activity relationship (SAR) and of the mechanism of action of illudalic acid was conducted.
A novel synthesis of the human leukocyte common antigen-related (LAR) phosphatase inhibitor, illudalic acid, has been achieved by a route more amenable to structure modifications. A series of simpler analogues of illudalic acid was synthesized and evaluated for potency in inhibiting LAR. The structure–activity relationship (SAR) study has shown that the 5-formyl group and the hemi-acetal lactone are crucial for effective inhibition of LAR activity, and are the key pharmacophores of illudalic acid. The fused dimethylcyclopentene ring moiety evidently helps to enhance the potency of illudalic acid against LAR. A preliminary study of the mechanism of action of illudalic acid against LAR was conducted using electrospray ionization mass spectrometry (ESI-MS) and molecular docking techniques. The results are in full agreement with the described mechanism.
Protein tyrosine phosphatases PTP-sigma （PTPo） plays an important role in the development of the nervous system and nerve regeneration. Although cumulative studies about the function of PTPo have ...been reported, yet limited data have been reported about the crystal structure and in vitro aetivity of mouse PTPcr. Here we report the crystal structure of mouse PTPcr tandem phos- phatase domains at 2.4 A, resolution. Then we compared the crystal structure of mouse PTPcr with human PTPcr and found that they are very similar, superimposing with a root mean square deviation of 0.45 A for 517 equivalent Ca atoms. But some residues in mouse PTPcr form loops while corresponding residues in human PTPcr form 3-sheets or o~-helices. Furthermore, we also compared in vitro activities of mouse PTPtr with human PTPcr and found that mouse PTPo has 25-fold higher specific activ- ity than human PTPcr does toward O-methyl fluorescein phosphate （OMFP） as the substrate. However, there is no significant activity difference between the mouse and the human enzyme detected with p-nitrophenylphosphate （pNPP） as the substrate. Mouse PTPo and human PTPa have different substrate specificities toward OMFP and pNPP as substrates. This work gives clues for further study of PTPa.
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