ß-Nicotinamide mononucleotide supplementation prolongs the lifespan of prematurely aged mice and protects colon function in ageing mice.

Ageing is defined as the degeneration of physiological functions in numerous tissues and organs of an organism, which occurs with age. As we age, the gut undergoes a series of changes and weaknesses that may contribute to overall ageing. Emerging evidence suggests that ß-nicotinamide mononucleotide (NMN) plays a role in regulating intestinal function, but there is still a lack of literature on its role in maintaining the colon health of ageing mice. In our research, Zmpste24-/- mice proved that NMN prolonged their life span and delayed senescence. This study was designed to investigate the effects of long-term intervention on regulating colon function in ageing mice. Our results indicated that NMN improved the pathology of intestinal epithelial cells and intestinal permeability by upregulating the expression of intestinal tight junction proteins and the number of goblet cells, increasing the release of anti-inflammatory factors, and increasing beneficial intestinal bacteria. NMN increased the expression of the proteins SIRT1, NMNAT2, and NMNAT3 and decreased the expression of the protein P53. It also regulated the activity of ISCs by increasing Wnt/ß-catenin and Lgr5. Our findings also revealed that NMN caused a significant increase in the relative abundance of Akkermansia muciniphila and Bifidobacterium pseudolongum and notable differences in metabolic pathways related to choline metabolism in cancer. In summary, NMN supplementation can delay frailty in old age, aid healthy ageing, and delay gut ageing.

L-arginine metabolism ameliorates age-related cognitive impairment by Amuc_1100-mediated gut homeostasis maintaining.

Aging-induced cognitive impairment is associated with a loss of metabolic homeostasis and plasticity. An emerging idea is that targeting key metabolites is sufficient to impact the function of other organisms. Therefore, more metabolism-targeted therapeutic intervention is needed to improve cognitive impairment. We first conducted untargeted metabolomic analyses and 16S rRNA to identify the aging-associated metabolic adaption and intestinal microbiome change. Untargeted metabolomic analyses of plasma revealed L-arginine metabolic homeostasis was altered during the aging process. Impaired L-arginine metabolic homeostasis was associated with low abundance of intestinal Akkermansia muciniphila (AKK) colonization in mice. Long-term supplementation of AKK outer membranes protein-Amuc_1100, rescued the L-arginine level and restored cognitive impairment in aging mice. Mechanically, Amuc_1100 acted directly as a source of L-arginine and enriched the L-arginine-producing bacteria. In aged brain, Amuc_1100 promoted the superoxide dismutase to alleviated oxidation stress, and increased nitric oxide, derivatives of L-arginine, to improve synaptic plasticity. Meanwhile, L-arginine repaired lipopolysaccharide-induced intestinal barrier damage and promoted growth of colon organoid. Our findings indicated that aging-related cognitive impairment was closely associated with the disorders of L-arginine metabolism. AKK-derived Amuc_1100, as a potential postbiotic, targeting the L-arginine metabolism, might provide a promising therapeutic strategy to maintain the intestinal homeostasis and cognitive function in aging.

A Randomized Double-blind Clinical Trial of Weierkang Pills for the Treatment of Chronic Atrophic Gastritis.

BACKGROUND AND GOALS: There are currently no standard treatments for chronic atrophic gastritis and traditional Chinese medicine may be effective. This study aims to investigate the efficacy and safety of Weierkang pills in treating chronic atrophic gastritis. MATERIALS AND METHODS: There were 108 patients in our study. They were randomly assigned to 2 groups. In group A, patients received Weierkang pills and patients in group B received folic acid combined with teprenone. Symptoms, endoscopic scores, and biopsy specimens were compared at baseline and 3 months after treatment. Meanwhile, the expressions of vascular endothelial growth factor and trefoil factor 3 (TFF3) in biopsy specimens were also compared. RESULTS: Our study showed that the total effective rates of atrophy/intestinal metaplasia in group A reached the same level as group B (51.7% vs. 40.0%, P =0.419). Weierkang significantly improved the total effective rate of atrophy/intestinal metaplasia in gastric angle compared with group B (64.7% vs. 33.3%, P =0.024). Weierkang can significantly lower the total Kyoto risk score (2.6±1.1 vs. 3.3±1.0, P =0.002) and atrophy score (1.4±0.6 vs. 1.8±0.5, P =0.001) after treatment. In addition, Weierkang improves symptoms (1.3±1.3 vs. 2.3±1.8, P =0.003) and epigastric pain (0.2±0.4 vs. 0.5±0.6, P =0.041). The expression of TFF3 in gastric mucosa decreased significantly after treatment with Weierkang ( P =0.002). CONCLUSIONS: Weierkang can improve the endoscopic appearance and pathologic changes of chronic atrophic gastritis patients. Symptoms also improved. TFF3 may be involved the pathophysiology mechanism.

Bifidobacterium adolescentis regulates catalase activity and host metabolism and improves healthspan and lifespan in multiple species.

To identify candidate bacteria associated with aging, we performed fecal microbiota sequencing in young, middle-aged and older adults, and found lower Bifidobacterium adolescentis abundance in older individuals aged ≥60 years. Dietary supplementation of B. adolescentis improved osteoporosis and neurodegeneration in a mouse model of premature aging (Terc-/-) and increased healthspan and lifespan in Drosophila melanogaster and Caenorhabditis elegans. B. adolescentis supplementation increased the activity of the catalase (CAT) enzyme in skeletal muscle and brain tissue from Terc-/- mice, and suppressed cellular senescence in mouse embryonic fibroblasts. Transgenic deletion of catalase (ctl-2) in C. elegans abolished the effects of B. adolescentis on the lifespan and healthspan. B. adolescentis feeding also led to changes in oxidative stress-associated metabolites in Terc-/- mouse feces. These results suggest a role for B. adolescentis in improving the healthspan and lifespan through the regulation of CAT activity and host metabolism.

Effect of Cuttlebone on Healing of Indomethacin-Induced Acute Gastric Mucosal Lesions in Rats.

The continuing use of nonsteroidal anti-inflammatory drugs (NSAIDs) usually increases the side effects such as peptic ulcer and acute gastric lesions in the gastrointestinal tract. Cuttlebone (CB), isolated from Sepiella maindroni de Rochebrune, was reported to have antioxidant activities, but its role in the treatment of indomethacin-induced gastric lesions has not yet been confirmed. In this research, we investigate the protective effect of cuttlebone on indomethacin-related ulcers in rats and possible mechanisms. Here, gastric ulcers were induced by oral administration of indomethacin, and then the rats were treated with omeprazole (4 mg/kg) or different doses (750, 1500, and 3000 mg/kg of body weight) of cuttlebone. We evaluated lesion index, inflammation score, and a series of oxidant/antioxidant parameters. The data demonstrated that cuttlebone could protect against gastric ulcers induced by indomethacin in a dose-dependent manner (positive correlation). Also, these effects were associated with attenuating the expression of malonaldehyde (MDA) and increasing the levels of some protective ingredients like epidermal growth factor (EGF), prostaglandin E2 (PGE2), and superoxide dismutase (SOD). Thus, considering its ability to protect indomethacin-induced acute gastric mucosal lesions and the underlying mechanisms, CB might be a potential candidate for treating gastric damage caused by NSAIDs.

The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial.

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with remodeling of gastric microbiota. However, comprehensive analyses of the impact of H. pylori infection, eradication therapy and probiotic supplementation on gut microbiota are still lacking. We aimed to provide evidence for clinical decision making. METHODS: Seventy H. pylori-positive and 35 H. pylori-negative patients (group C) were enrolled. H. pylori-positive patients were randomly assigned to group A (14-day bismuth-containing quadruple therapy) and group B (quadruple therapy supplemented with Clostridium butyricum). Stool samples of group A and B were collected on day 0, 14 and 56 while stool samples of group C were collected on day 0. Gut microbiota was investigated by 16S rRNA sequencing. FINDINGS: The Sobs index (richness estimator) was significantly higher in H. pylori-positive samples than H. pylori-negative samples (p < .05). Several metabolic pathways were more abundant in H. pylori-positive communities while some disease-associated pathways had higher potential in H. pylori-negative community through KEGG pathway analysis. Abundances of most butyrate-producing bacteria significantly decreased, while several detrimental bacteria increased after eradication therapy. Probiotic supplementation was associated with improved gastrointestinal symptoms as well as increased Bacteroidetes:Firmicutes ratio. INTERPRETATION: While H. pylori infection may not be necessarily detrimental in all patients, eradication of H. pylori was associated with widespread changes in gut microbial ecology and structure. Probiotic supplementation could relieve more gastrointestinal symptoms by inducing alterations in gut microbiota and host immune responses. As such, the decision to eradicate H. pylori should be based on comprehensive analysis of individual patients.

Akt associates with nuclear factor kappaB and plays an important role in chemoresistance of gastric cancer cells.

The ubiquitously expressed serine-threonine kinase Akt and the transcription factor NF-kappaB both are involved in cell proliferation and apoptosis. Furthermore, the activation of Akt or NF-kappaB has been suggested to associate with chemo-resistance of human tumors. The exact mechanism and interreaction of Akt and NF-kappaB pathway on chemoresistance in gastric cancer is still unknown. We explored the function of Akt and NF-kappaB pathway on chemoresistance in human gastric cancer cells. MTT method was used to analyze the influence of chemotherapeutics and the combined use of wortmannin or MG-132 on the growth of SGC-7901 cells. Apoptosis of SGC-7901 was detected by TUNEL and Annexin V/PI methods. The protein level of NF-kappaB was analyzed by immunocytochemical staining. EMSA was used to confirm the increased nuclear translocation of RelA. The protein level of p-Akt and p-IkappaBalpha were analyzed by Western blotting. Etoposide and doxorubicin suppressed the growth of SGC-7901 time and dose-dependently. Combined use of wortmannin or MG-132 can suppress growth further. Chemotherapeutics induced apoptosis of SGC-7901 and activated Akt and NF-kappaB, combined use of wortmannin or MG-132 induced apoptosis further and attenuated the activation of NF-kappaB. The combined use of wortmannin attenuated the activation of Akt, but combined use of MG-132 did not attenuate the activation of Akt. The activation of NF-kappaB is a branch mechanism of Akt anti-apoptosis effects. The chemotherapeutics induced apoptosis and induced the activation of Akt and NF-kappaB in SGC-7901 cell, suppression the activation of Akt or NF-kappaB can increase the effects of chemotherapeutics. NF-kappaB is a downstream target of Akt.

Effect of mica monomer powder on chief and parietal cells as well as G and D cells in gastric mucosa of chronic atrophic gastritis in rats.

OBJECTIVE: To study the regulative action of mica monomer powder preparation on the chief and parietal cells as well as G and D cells in the gastric mucosa of the experimental atrophic gastritis (CAG) rats. METHODS: Intervention therapy was given to the experimental CAG rats at three different doses of mica monomer powder preparation to evaluate the changes of chief and parietal cells as well as G and D cells in the gastric mucosa and the histopathological changes of gastric mucosa. RESULTS: Mica monomer powder preparation at three different doses could increase the amount of chief and parietal cells as well as G and D cells in gastric mucosa of the experimental CAG rats and alleviate and control the inflammation of gastric mucosa and the atrophy of gastric mucosa glands. Especially, better effects were shown in the mid and high dose groups. CONCLUSION: Mica has the pharmacological action of protecting the gastric mucosa, enhancing blood flow of the gastric mucosa, and consequently improving the inflammatory responses of the gastric mucosa. One of the mechanisms is associated with promoting the secretion of gastric acid and gastric pepsin and regulating the neuroendocrine mechanism including gut hormone secretion (gastrin and somatostatin) by increasing the number of chief and parietal cells as well as G and D cells.

[Effect of mica granule on the expression of gene-protein associated with cancer in gastric mucosa tissue of chronic atrophic gastritis rats].

OBJECTIVE: To research the regulative effect of mica monomer granule preparation on the expression of gene associated with cancer in gastric mucosa tissue of experimental chronic atrophic gastritis (CAG) rats. METHOD: To treat experimental CAG rats using mica monomer granule preparation with three different dosage-high, moderate and low level respectively. To observe the expression changes of mutant antioncogene-p53 gene-protein, oncogene p21, antioncogene p16 and anti-apoptosis gene bcl-2 in gastric mucosa of CAG rats by two-step ways of EnVision system in immunohistochemical method. RESULT: There was the tendency that mica monomer granule preparation with three different dosage could decrease the expression of p53 as well as p21, and mica had the obvious regulative effects on deletion of p16 and high-expression of bcl-2. It could also alleviate the inflammation of gastric mucosa and promote the regeneration of gland. CONCLUSION: The treatment and reversion action of mica on chronic atrophic gastritis is probably related with the regulative effect on the expression of gene associated with cancer.

[The effect of muscovite on the quality of gastric ulcer healing].

OBJECTIVE: To explore the effect of muscovite on the quality of gastric ulcer healing. METHOD: Gastric ulcers were produced in male rats by serosal application of acetic acid. Rats were gavaged for 14 days with saline, omeprazole and muscovite starting 3 days after ulcer induction. Then the tissue and blood samples were obtained and measured. RESULT: In the muscovite group, restored mucosa thickness increased, cystically dilated glands decreased, microvessels in connective tissue increased, the secretion of mucus, hexosamine, PGE2, EGF, bFGF were enhanced, and the express of EGFR was stronger. CONCLUSION: Muscovite can promote the gastric ulcer healing and improve the quality of gastric ulcer healing.

Regulative effect of traditional Chinese medicine on gene-expression related to precancerous lesion of gastric cancer.

The gene-expression changes related with precancerous lesion of gastric cancer (PLGC) are surveyed. Not only the regulative effect of traditional Chinese medicine (TCM) on oncogene, antioncogene and anti-apoptosis gene that are related with PLGC is analyzed, but also current research state is presented. It's showed that TCM has effects of therapy and inversion on PLGC. These effects are related with the inhibition to related oncogene expression, the regulation and activation to the deletion of antioncogene, the inhibition to the high-expression of mutant gene-protein about antioncogene, and the regulative function to anti-apoptosis gene.

[Intestinal mucosa protection of muscovite n ulcerative colitis in rats].

OBJECTIVE: To examine the efficacy of Muscovite on acetic acid-induced ulcerative colitis in rats, and to research the mechanisms of intestinal mucosal protection. METHOD: Ulcerative colitis was induced in rats by intracolonic injection of 2 mL of 7% acetic acid. Rats were treated with three different doses of the Muscovite and SASP at random by intracolonic injecion, the normal saline was considered as control group. The rats were sacrificed and the colons were excised and opened longitudinally. Under a dissecting microscope, gross findings were observed and scored. MPO activity was assayed by spectrophotometry in colonic mucosa. RESULT: Gross finding showed that multiple ulcer with diameter more than 1 cm, surrounded with erosion, erythematous and edema in the proximal colon in ulcerative coltis. The colon from Muscovite treatment group were histopatholgically normal, with slight erosion, erythematous and edema. The colon in SASP group had small ulceration and severe erosion and edema. The score of gloss change were significant lower in Muscovite groups than that in normal saline group (P < 0.01). There were necrosis and exfoliation of mucosa, multiple cystic dilation of mucosa gland, and large number of and inflammation attenuated in Muscovite groups. There nerutrophils and vessel infiltration in ulcerative colitis. The ulceration disappeared were erosion in mucosa and inflammatory cell infiltrating into submucosa in SASP group. Compared with normal saline group, the pathological scale were significant decreased in Muscovite and SASP groups (P < 0.05). The MPO activity was significant increased in colitis tissue compared with normal group (P < 0.001). After administrating with Muscovite or SASP, the level of MPO were significant decreased (P < 0.01). CONCLUSION: Muscovite has the effect of mucosal protection by attenuating the inflammation of colonic mucosa and decreasing the activity of MPO.

[Mechanism of isinglass in prevention and treatment of chronic atrophic gastritis in rats].

OBJECTIVE: To investigate the mechanism of isinglass in the prevention and treatment of chronic atrophic gastritis (CAG) in rats. METHOD: Animal models of SD rats with CAG were made in accordance with the previous experience of combined administration of 60% ethanol, 20 mmol x L(-1) sodium deoxycholate and 0.1% ammonia water. In prevention groups, sucralfate and isinglass were used as preventive therapy while CAG rat model was being made. In the reverse groups, sucralfate and isinglass were used to treat rats after establishment of CAG rat model. Finally all the rats were executed. Then the length of the proliferation zone of the gastric mucosa and serum epidermal growth factors (EGF) and growth hormones (GH)level were studied. RESULT: In isinglass prevention groups and high dose isinglass reverse group, the length of the proliferation zone of the gastric mucosa was very close to that in normal control group (P > 0.05), much better than model control group (P < 0.01). In low dose isinglass reverse group, it was lower than that in normal control group (P < 0.01), but much better than model control group (P < 0.01). In both prevention and reverse groups, serum EGF level was higher than that in normal (P < 0.01) and model control group (P < 0.05). Serum GH level was the same in every group (P > 0.05). CONCLUSION: The mechanism of isinglass in the prevention and treatment of CAG rats lies in revitalizing and proliferating gastric mucosal cells by stimulating endogenous EGF secretion.

[Mechanisms of muscovite on gastric mucosal protective effect].

OBJECTIVE: To explore the mechanisms of muscovite gastric mucosal protective effect. METHOD: Rat model of chronic gastritis were used. After gastric mucosal injury was induced, the rats were divided into 6 groups and were treated with different drugs. 2 weeks later, the tissue and blood samples were obtained and measured. RESULT: The general conditions, the observations under macroscopy, microscope and electron microscope of the middle and high dose of muscovite groups resembled those of the normal group. Their PH levels were higher than those of the model group, and the rates of intestinal metaplasia were lower, but the PGE2 level of the middle dose of muscovite group was the highest. CONCLUSION: Muscovite can be adsorbed on the surface of the gastric mucosa. It has gastric mucosal protective effect by improving excretion of mucus and synthesis of PGE2 in gastric mucosa, restraining gastric acid, reversing of intestinal metaplasia and decreasing inflammation cells.

[Prevention and treatment of chronic atrophic gastritis in rats with isinglass].

OBJECTIVE: To evaluate the effect of isinglass on the prevention and treatment of chronic atrophic gastritis in rats. METHOD: Animal model of SD rats with CAG was established in accordance with the previous experience of combined administration of 60% ethanol, 20 mmol x L(-1) sodium deoxycholate and 0.1% ammonia water. In prevention groups, sucralfate and isinglass were used as preventive therapy while we were establishing CAG rat model. In the reverse groups, sucralfate and isinglass were used to treat rats after establishment of CAG rat model. Finally all the rats were executed and pathologic changes of the gastric mucosa were studied by gross appearance and microscopy. RESULT: In isinglass prevention groups and reverse groups, inflammation grades of gastric antrum were less than these in model control group (P < 0.01) while the means of ratios of the thickness of gastric mucosal gland and muscularis mucos (L1/L2), the number of gastric glands in 1-mm lengths of mucosal layer were much better than those in model control group (P < 0.01). They were very close to normal control group (P > 0.05). CONCLUSION: Isinglass can prevent the gastric mucosal atrophy in the CAG model and can improve and cure the gastric mucosal atrophy of the SD rats with GAG.

[Effect of mica monomer granule on gastrin, somatostatin and G cells as well as D cells of gastric mucosa in CAG rat].

OBJECTIVE: To study regulative action of mica monomer granule preparation on gastrin (GAS), somatostatin (SS) and G cells as well as D cells of gastric mucosa in experimental chronic atrophic gastritis (CAG) rat. METHOD: CAG rats were treated with mica monomer granule preparation with three different dosages--high, moderate and low level respectively. Changes of blood serum GAS, blood plasma SS and G cells as well as D cells of gastric mucosa in CAG rats were observed and detected with ELISA method, RIA method and immunocytochemistry method. RESULT: Mica monomer granule of three different dosages could increase the quantity of G cells as well as D cells of gastric mucosa and the concentration of blood serum GAS and decrease the content of blood plasma SS in CAG rat at different level respectively. It was more effective in high and moderate dosage groups. CONCLUSION: Mica has the pharmacological action of protecting gastric mucosa, promoting the palingenesis of gastric gland and enhancing blood stream of gastric mucosa consequently to abate the inflammation reaction of gastric mucosa. Its effective mechanism is associated with the neuroendocrine regulative mechanism of promoting the secretion of gastric acid and gastric pepsin by increasing the amount of G cells as well as D cells and the concentration of blood serum GAS, and reducing inhibiting action on GAS secretion and enhancing the secretion of GAS by decreasing the content of SS.