Diabetes, metformin and gastric adenocarcinoma

Diabetes may increase the risk and mortality of certain cancers, but its association with gastric adenocarcinoma is not clear. On the other hand, metformin, a first-line treatment for diabetes, may reduce cancer risks and improve cancer-related survival, but these associations have not been confirmed in gastric adenocarcinoma as well. The aim of this thesis is to evaluate if and how diabetes or its biomarkers and the use of metformin influence the risk and prognosis of gastric adenocarcinoma. Study I investigated if diabetes or prediabetes influenced the risk of gastric adenocarcinoma in a population-based Swedish cohort. Participants of the Northern Swedish Health and Disease Study were included and followed up from 1985 to 2017. Participants exposed to diabetes or prediabetes, as confirmed by self-reports or oral glucose tolerance tests, were compared with those of normoglycaemia for the incidence of gastric adenocarcinoma, identified from the Swedish Cancer Registry. Cox proportional hazard regression analyses with adjustment for sex, age, calendar year, body mass index, tobacco smoking, and education level showed no associations between prediabetes or diabetes and the risk of gastric adenocarcinoma (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.79-1.44 for prediabetes; HR 0.77, 95% CI 0.46-1.29 for diabetes). Study II was a systematic review and meta-analysis assessing associations between serum Haemoglobin A1c (HbA1c) or glucose and the risk of developing gastric cancer, based on studies identified from three databases: MEDLINE, Embase and Cochrane library. The random-effects model showed that elevated levels of serum HbA1c were associated with an increased risk of gastric cancer (pooled HR 1.36, 95% CI 1.06-1.74), but not so for elevated levels of serum glucose (pooled HR 1.11, 95% CI 0.98-1.26). Study III was a population-based cohort study evaluating whether diabetes worsened the prognosis in gastric adenocarcinoma, including all patients diagnosed with gastric adenocarcinoma between 1990 and 2014 in Sweden. Co-existing diabetes at diagnosis of gastric adenocarcinoma was analysed by the Cox proportional hazard regression with the risk of mortality due to gastric adenocarcinoma (disease-specific mortality) as well as all-cause mortality. The HRs were adjusted for sex, age, calendar year, and co-morbidity. Patients with diabetes at diagnosis had a moderately increased risk of disease-specific mortality compared with those without diabetes (HR 1.17, 95% CI 1.11-1.22). Besides, diabetes was also associated with an increased risk of all-cause mortality among patients who underwent gastrectomy for gastric adenocarcinoma (HR 1.23, 95% CI 1.10-1.38). Study IV was a population-based cohort study assessing whether metformin use decreased the risk of gastric adenocarcinoma. All data were retrieved from four national health data registries and participants were selected from users of certain commonly prescribed medications. Two sub-cohorts were established, a diabetes cohort and a matched cohort. Cox proportional hazard regressions with adjustment for sex, age, calendar year, comorbidity, Helicobacter pylori eradication treatment, use of non-steroidal anti-inflammatory drugs, and use of statins were used to compare users and non-users of metformin in relation to the risk of gastric non-cardia and cardia adenocarcinoma. The risk of gastric non-cardia adenocarcinoma was not decreased among metformin users compared with non-users in either sub-cohorts (HR 0.93, 95% CI 0.78-1.12 in the diabetes cohort; HR 1.30, 95% CI 1.18-1.42 in the matched cohort). Besides, metformin use did not decrease, but rather increased the risk of gastric cardia adenocarcinoma in either sub-cohorts (HR 1.49, 95% CI 1.09-2.02 in the diabetes cohort; HR 1.58, 95% CI 1.38-1.81 in the matched cohort). Study V was a population-based cohort study aiming to test if pre-diagnosis use of metformin improved the prognosis in gastric adenocarcinoma. The study included all diabetes patients who were diagnosed with gastric adenocarcinoma between 2005 and 2018. Associations between metformin use within two years before the diagnosis of gastric adenocarcinoma and the risk of disease-specific and all-cause mortality were analysed with Cox proportional hazard regressions, with adjustment for sex, age, calendar year, comorbidity, use of non-steroidal anti-inflammatory drugs, and use of statins. Metformin use was associated with a decreased risk of disease-specific mortality (HR 0.79, 95% CI 0.67- 0.93) and all-cause mortality (HR 0.78, 95% CI 0.68-0.90) among diabetes patients with gastric adenocarcinoma. To conclude, diabetes or prediabetes did not increase the risk of gastric adenocarcinoma in the Swedish population of Study I, but aggregated evidence indicated that long-term hyperglycaemia may increase the risk of gastric cancer (Study II). Gastric adenocarcinoma patients with co-existing diabetes had a higher risk of disease-specific mortality compared with those without diabetes (Study III). Besides, although metformin use might not prevent gastric adenocarcinoma (Study IV), it may improve the prognosis of this cancer among diabetes patients (Study V)

Impact of muscle strength ladder training on disabled elders

BackgroundCurrently, there are many studies focusing on the physical activity program of disabled elders, but little is known about effective and cheap appliances for the disabled elderly to take home exercise.AimsTo evaluate the impact of muscle strength ladder training on the activity ability of disabled elders.Methods A self-control trial was applied to 35 disabled elders in the communities in Shanghai for three months. The patients were evaluated for muscle strength and daily living activity (ADL) at the time of entry and intervention for three months.Results After the intervention, the patient's muscular strength grade was improved (P < 0.01), and the activity ability score was increased (P < 0.01).ConclusionMuscle strength ladder training could improve the muscle strength and activity ability of the upper and lower extremities. With the help of the muscle strength ladder training, the convenience, effectiveness and safety of exercise training could be increased

Visible Light-Driven Organic Pollutant Removal Using Fe-Based Photocatalysts Supported by Wheat Straw Biochar

Researchers are actively pursuing the development of highly functional photocatalyst materials using environmentally friendly and sustainable resources. In this study, wheat straw biochar (BC), a by-product of biomass pyrolysis, was explored as a green, porous substrate and a carbon-based sensitizer to activate Fe-based photocatalysts under visible light. The research also delved into the impact of doping copper (Cu), chromium (Cr), and zinc (Zn) to enhance the photocatalytic activity of BC-Fe-based catalysts for the removal of methylene orange (MO) from water. Characterization results revealed a more than twofold increase in surface area and greater porosity, contributing to improved radical generation. BC demonstrated its dual functionality as a high surface area substrate and an electron sink, facilitating multistep electron movement and enhancing the photoactivity of the composite catalyst. Photodegradation experiments indicated that the combination of BC with Fe and Zn exhibited the highest performance, removing over 80% of MO within 120 min. Parametric studies highlighted the preference for an alkali pH, and the photocatalyst demonstrated efficient performance up to 30 ppm of dye. Radical scavenging experiments identified •OH and h+ as the most generated radicals. This study establishes that the green and sustainable BC holds promise as a material in the quest for more sustainable photocatalysts

Ginsenoside 20(S)-Rg3 Prevents PKM2-Targeting miR-324-5p from H19 Sponging to Antagonize the Warburg Effect in Ovarian Cancer Cells

Background/Aims: The Warburg effect is one of the main metabolic features for cancers, with long non-coding RNA (lncRNA) being involved as a class of crucial regulators. Our previous studies have shown that ginsenoside 20(S)-Rg3, an active saponin monomer extracted from red ginseng, inhibits the Warburg effect in ovarian cancer cells. However, the detailed lncRNA regulatory network modulated by 20(S)-Rg3 to prevent the Warburg effect in ovarian cancer cells has not been explored. Methods: High-throughput sequencing was used to screen out the differentially expressed lncRNAs between 20(S)-Rg3-treated and non-treated SKOV3 cells. The levels of lncRNA H19 and miR-324-5p were manipulated in SKOV3 and A2780, and the glucose consumption, lactate production and PKM2 protein level were detected. Dual-luciferase reporter assay and RIP were utilized to verify the direct binding of H19 to miR-324-5p and miR-324-5p to PKM2. Cell proliferation was examined by CCK8 and colony formation assay. Nude mice subcutaneous xenograft tumor models were established to evaluate the impact of miR-324-5p on tumor growth in vivo. Results: 20(S)-Rg3 downregulated 67 lncRNAs, and H19 was one of the most decreased lncRNAs. Suppression of H19 by siRNA transfection reduced glucose consumption, lactate production and PKM2 expression in ovarian cancer cells, while H19 overexpression in 20(S)-Rg3-treated ovarian cancer cells enhanced glucose consumption, lactate production and PKM2 expression. Dual-luciferase reporter assay and RIP results showed that H19 directly bound to miR-324-5p. Dual-luciferase reporter assay showed that miR-324-5p directly targeted PKM2, and miR-324-5p negatively regulated glucose consumption and lactate production in ovarian cancer cells. miR-324-5p overexpression inhibited cell proliferation in vitro and in vivo. Conclusion: Our study revealed that 20(S)-Rg3 blocked the competitive inhibition of H19 on miR-324-5p, which enhanced the suppression of miR-324-5p on PKM2 and therefore inhibited the Warburg effect and repressed tumorigenesis. In a word, 20(S)-Rg3 inhibited the Warburg effect in ovarian cancer cells via H19/miR-324-5p/PKM2 pathway

A review of the botany, ethnopharmacology, phytochemistry, analysis method and quality control, processing methods, pharmacological effects, pharmacokinetics and toxicity of codonopsis radix

Codonopsis Radix, a traditional Chinese medicine in China, has great medicinal and scientific value. Moreover, it can also be used as a health product in daily diet. This paper reviews the botany, ethnopharmacology, phytochemistry, analysis method and quality control, processing methods, pharmacological effects, pharmacokinetics and toxicity related to Codonopsis Radix. The information of Codonopsis Radix is obtained from scientific databases (such as Baidu Scholar, CNKI, Google Scholar, PubMed, Science Direct, Web of Science, and SciFinder Scholar), Chinese herbal classics, Chinese Pharmacopoeia, PhD and MSc dissertations, and so on. The chemical components mainly include alkaloids, alkynes and polyacetylenes, flavonoids, lignans, steroids, terpenoids, organic acids, volatile oils, saccharides and other components, which have a wide range of neuroprotective effects, protection of gastrointestinal mucosa and anti-ulcer, regulation of body immunity, anti-tumor, endocrine regulation, improvement of hematopoietic function, cardiovascular protection, anti-aging and antioxidant effects. In conclusion, this paper summarizes in depth the shortcomings of the current research on Codonopsis Radix and proposes corresponding solutions. At the same time, this paper provides theoretical support for further research on the biological function and potential clinical efficacy of Codonopsis Radix

Whole Brain Mapping of Long-Range Direct Input to Glutamatergic and GABAergic Neurons in Motor Cortex

Long-range neuronal circuits play an important role in motor and sensory information processing. Determining direct synaptic inputs of excited and inhibited neurons is important for understanding the circuit mechanisms involved in regulating movement. Here, we used the monosynaptic rabies tracing technique, combined with fluorescent micro-optical sectional tomography, to characterize the brain-wide input to the motor cortex (MC). The whole brain dataset showed that the main excited and inhibited neurons in the MC received inputs from similar brain regions with a quantitative difference. With 3D reconstruction we found that the distribution of input neurons, that target the primary and secondary MC, had different patterns. In the cortex, the neurons projecting to the primary MC mainly distributed in the lateral and anterior portion, while those to the secondary MC distributed in the medial and posterior portion. The input neurons in the subcortical areas also showed the topographic shift model, as in the thalamus, the neurons distributed as outer and inner shells while the neurons in the claustrum and amygdala were in the ventral and dorsal part, respectively. These results lay the anatomical foundation to understanding the organized pattern of motor circuits and the functional differences between the primary and secondary MC

Study on Formulation, in vivo Exposure, and Passive Targeting of Intravenous Itraconazole Nanosuspensions

The pharmacokinetic profile of a drug can be different when delivered as a nanosuspension compared with a true solution, which may in turn affect the therapeutic effect of the drug. The goal of this study was to prepare itraconazole nanosuspensions (ITZ-Nanos) stabilized by an amphipathic polymer, polyethylene glycol-poly (benzyl aspartic acid ester) (PEG-PBLA), by the precipitation-homogenization, and study the pharmacokinetic profile of the ITZ-Nanos. The particle size and morphology of nanosuspensions were determined by Zetasizer and field emission scanning electron microscope (SEM), respectively. The dissolution profile was evaluated using a paddle method according to Chinese Pharmacopoeia 2015. The level of ITZ in plasma and tissues was measured by a HPLC method. The optimized ITZ-Nanos had an average particle size of 268.1 ± 6.5 nm and the particles were in a rectangular form. The dissolution profile of ITZ-Nanos was similar to that of commercial ITZ injections, with nearly 90% ITZ released in the first 5 min. The ITZ-Nanos displayed different pharmacokinetic properties compared with the commercial ITZ injections, including a decreased initial drug concentration, increased plasma half-life and mean residence time (MRT), and increased concentration in the liver, lung, and spleen. The ITZ-Nanos can change the in vivo distribution of ITZ and result in passive targeting to the organs with mononuclear phagocyte systems (MPS)