Inhibited Weight Loss Research Articles

Mare milk and fermented mare milk alleviate DSS-induced ulcerative colitis in mice by reducing inflammation and modulating intestinal flora.

Mare milk (MM) and fermented mare milk (FM) are specialized animal milks with high nutritional value, containing a variety of functionally active substances that are capable of resisting inflammatory responses and oxidative stress. However, researches on the maintenance of intestinal homeostasis have been insufficient. This study aimed to investigate the effects of MM and FM on the prevention of DSS-induced ulcerative colitis in a mouse model and to preliminarily elucidate the underlying mechanisms. The results showed that MM and FM had different degrees of protective effects against the damage of DSS and alleviated ulcerative colitis by inhibiting weight loss, reducing colon length shortening, and restoring intestinal structure. Additionally, MM and FM maintained intestinal tight junction protein levels to repair barrier function, downregulated inflammatory cytokines (e.g., IL-1β, TNF-α, IL-6, and iNOS) and bolstered the body's antioxidant defense system. Moreover, MM and FM regulate the dysregulation of intestinal microenvironment by improving gut microbiota diversity and reshaping its structure, including increasing the proportion of Firmicutes and Bacteroidetes and the relative abundance of beneficial bacterial genera (e.g., Akkermansia). In summary, mare milk and fermented mare milk can serve as a dietary resource for preventing ulcerative colitis and maintaining intestinal homeostasis.

Poly(vinyl alcohol)-based multifunctional smart packaging films with carbon dots-loaded metal-organic frameworks for freshness indicator and shelf-life extension of shrimp

This study aims to fabricate poly(vinyl alcohol)-based films (PVA-based films) incorporated with carbon dots-loaded metal-organic frameworks (CD@MOF) for freshness indicator and shelf life extension of shrimp. Incorporation of CD@MOF to PVA-based composite films (PVA/CD@MOF) showed excellent antimicrobial and antioxidant activities with 77.44 % ABTS radical scavenging efficiency. Additionally, the composite films showed a superior UV-barrier of 99.48 % compared to 23.28 % for neat PVA film. The color of PVA/CD@MOF composite films changed from green to blue when exposed to ammonia. In shrimp freshness monitoring tests, the color of PVA/CD@MOF composite films turned brown simultaneously with changes in the chemical parameters of shrimp, providing a visual indication of changes in the quality of stored shrimp. Additionally, PVA/CD@MOF films effectively inhibited weight loss, pH increase, microbial growth, and oxidation of stored shrimp. These results imply that CD@MOF can serve effectively as a dual-purpose active and indicator additive in practical packaging materials.

Laoxianghuang polysaccharide promotes the anti-inflammatory cytokine interleukin-10 in colitis via gut microbial linoleic acid

BackgroundOur previous study found that the polysaccharide from Laoxianghuang (LP), fermented fruit of bergamot (traditional Chinese medicine and food), can alter gut microbiota and regulate short-chain fatty acids (SCFAs) in vitro. Nevertheless, there is a paucity of reports on the impact of LP on gut microbiota in vivo. PurposeTo analyze the structures of LP, investigate the influence of LP on the damaged intestinal barrier in DSS-induced colitis mice, and further explore its potential mechanisms. MethodsWe analyzed the physicochemical properties of purified LP by HPLC, SEM, and FT-IR spectrum. Then, to assess the effect of LP in DSS-induced colitis mice, we observed the damage to the colon tissue, measured inflammatory cytokines and tight junction protein expression through RT-qPCR as well as immunofluorescent staining, and investigated the influence of LP on altering gut microbiota and metabolites using 16 s rRNA sequencing and HPLC-MS/MS. Ultimately, the impact of linoleic acid on inflammatory cytokines was confirmed by the LPS-induced RAW264.7 cells. ResultsLP, mainly galactoglucan, could inhibit weight loss and colon shortening, decrease levels of tumor necrosis factor-α (TNF-α), increase levels of interleukin-10 (IL-10) and the intestinal acetic acid and butyric acid, and promote the expression of tight junction proteins ZO-1 and Claudin-1. Meanwhile, LP enhanced the abundance of beneficial bacteria including Romboutsia, Eubacterium_coprostanoligenes_group, and Akkermansia, and regulated linoleic acid metabolism to increase the linoleic acid level. In vitro cell experiment proved that linoleic acid could elevate the level of IL-10 and inhibit inflammatory responses. ConclusionsOur results suggested that LP effectively alleviated colitis by promoting the anti-inflammatory cytokine interleukin-10 via gut microbiota-mediated linoleic acid metabolism.

Laminaria japonica Polysaccharide Regulates Fatty Hepatosis Through Bile Acids and Gut Microbiota in Diabetes Rat.

In this study, we examined the effect of Laminaria japonica polysaccharide (fucoidan) on the regulation of lipid metabolism. A rat model of diabetes mellitus (DM) was established by a high-sugar and high-fat diet combined with streptozotocin. Changes in the rats' body weight and blood glucose level during the experiment were recorded. Before the end of the experiment, an automatic biochemical analyzer was used to detect the fasting blood glucose (FBG), lipid content in serum, and insulin content, and calculate the insulin resistance index. Oil red O staining was used to detect lipid deposition in the liver. H&E staining, Masson staining, and PASM staining were used to observe the pathological structural changes in the liver. 16s RNA sequencing and targeted metabolomics were used to detect intestinal microbiota and bile acid content. The results showed that fucoidan was able to inhibit weight loss in the DM rats and reduce the content of triglycerides (TG), cholesterol (TC), and low-density lipoprotein (LDL-C) in serum. Oil red O staining showed a decrease in liver fat accumulation after fucoidan treatment. 16s RNA sequencing demonstrated that fucoidan increased the abundance of Bacteroidia, Campylobacteria, Clostridia, Gammaproteobacteria, Negativicutes, and Verrucomicrobi. Fucoidan also increased the secretion of secondary bile acids (Nor-DCA, TLCA, β-UDCA) and alleviated lipid metabolism disorders. The expression of α-SMA was inhibited by fucoidan, whereas the expression of FXR and TGR5 was promoted. Fucoidan shows good activity in regulating lipid metabolism by regulating the expression of FXR and TGR5 and acting on the intestinal flora-bile acid axis.

Deer oil improves ulcerative colitis induced by DSS in mice by regulating the intestinal microbiota and SCFAs metabolism and modulating NF-κB and Nrf2 signaling pathways.

Deer oil (DO), a byproduct of deer meat processing, possesses high nutritional value. This study aims to evaluate the protective effects of DO on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and to explore its potential mechanisms of action. DO was found to inhibit weight loss and colon shortening in colitis mice, significantly reduce disease activity index scores, and notably enhance the levels of tight junction proteins in colon tissues, thus improving intestinal barrier function. ELISA results indicated that DO markedly alleviated the mice's oxidative stress and inflammatory responses. Western blot analysis further demonstrated that DO significantly inhibited the phosphorylation of NF-κB while up-regulating the expression levels of Nrf2 and HO-1 proteins. Additionally, DO increased the abundance of beneficial bacteria such as Odoribacter, Blautia, and Muribaculum, reduced the abundance of harmful bacteria such as Bacteroides, Helicobacter, and Escherichia-Shigella, and promoted the production of short-chain fatty acids. Our study provides the first evidence that DO can effectively improve DSS-induced UC in mice. The underlying mechanisms may involve maintaining intestinal barrier function, inhibiting inflammation, alleviating oxidative stress, and modulation of gut microbiota. These findings offer valuable insights for developing DO as an adjunct treatment for UC and as a functional food. © 2024 Society of Chemical Industry.

The effect of novel paraprobiotic cocktail on dextran sodium sulfate induced acute colitis control focusing on autophagy signaling pathway.

Paraprobiotics are a non-viable form of probiotics that are reported to provide significant health benefits. Nevertheless, little is known about the beneficial effects of paraprobiotics on inflammatory bowel disease. Although probiotics show potential as therapeutic agents for a range of diseases, including inflammatory bowel disease (IBD), there are certain risks associated with their use. These risks include toxin production, hemolytic potential, antibiotic resistance, and the need to analyze metabolic activities. Hence Using paraprobiotic with the lower aforementioned risk would therefore be the preferable option. Here, we conducted an in vivo study to evaluate the preventive effect of our native paraprobiotic cocktail against dextran sulfate sodium (DSS)-induced murine colitis by affecting the autophagy signaling pathway. Four-week-old male C57Bl/6 mice were randomly divided into three groups after a two-week acclimation period with normal standard laboratory food diet. Mice were administered PBS (PBS group as control), PBS along with DSS (DSS group, as a control), and a cocktail of paraprobiotics along with DSS (Para group). The severity of colitis, length and histopathology of the colon were evaluated. In addition, the expression of autophagy was assessed using real-time PCR. The results showed that administration of the paraprobiotic cocktail to DSS-treated mice inhibited the severity of colitis symptoms, as evidenced by the inhibition of weight loss and DAI, as well as histopathological scores in the study colon, as well as shortening of colon length caused by DSS. In contrast to the DSS group, the cocktail was able to modulate inflammation through upregulation of autophagy-related genes (becline 1, atg5, atg7, atg12, and atg13). Although there are some limitations in our investigation, such as the dosage and duration of treatments, our native paraprobiotic blend effectively prevented the advancement of colitis. This suggests that it plays a vital role in regulating inflammation and preventing colitis by promoting the autophagy mechanism in cases where the consumption of probiotics may have negative consequences.

Inadequate insurance coverage for overweight/obesity management.

To discuss the social, psychological, and access barriers that inhibit weight loss, and to propose steps and initiatives for addressing the growing obesity epidemic. Narrative review of the obesity epidemic in the US and associated racial/ethnic and socioeconomicdisparities. An internet search of relevant studies and government reports was conducted. Obesity is a significant health crisis affecting more than 123 million adults and children/adolescents in the US. An estimated 1 in 5 deaths in Black and White individuals aged 40 to 85 years in the US is attributable to obesity. Obesity puts individuals at elevated risk for type 2 diabetes, cardiovascular disease, chronic kidney disease, gastrointestinal disorders, nonalcoholic fatty liver disease, cancer, respiratory ailments, dementia/Alzheimer disease, and other disorders. In the US, significantly more Black (49.9%) and Hispanic (45.6%) individuals are affected by obesity than White (41.4%) and Asian (16.1%) individuals. Health care costs for obesity account for more than $260billion of annual US health care spending-more than 50% greater in excess annual medical costs per person than individuals with normal weight. Addressing the obesity epidemic will require a multifaceted approach that focuses on prevention, treatment, and reducing the impact of stigma. Continued advocacy and education efforts are necessary to make progress and improve the health and well-being of individuals affected by obesity.

Sinomenine hydrochloride improves DSS-induced colitis in mice through inhibition of the TLR2/NF-κB signaling pathway

BackgroundSinomenine hydrochloride (SH) has anti-inflammatory and immunosuppressive effects, and its effectiveness in inflammatory diseases, such as rheumatoid arthritis, has been demonstrated. However, whether SH has a therapeutic effect on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice and its mechanism of action have not been clarified. This study aimed to investigate the therapeutic effects and mechanism of action of SH on UC. MethodsTwenty-four mice were randomly divided into control, model, SH low-dose (SH-L, 20mg/kg), and SH high-dose (SH-H, 60mg/kg) groups with six mice in each group. Disease activity index (DAI), colonic mucosal damage index, and colonic histopathology scores were calculated. The expression levels of related proteins, genes, and downstream inflammatory factors in the Toll-like receptor 2/NF-κB (TLR2/NF-κB) signaling pathway were quantified. ResultsSH inhibited weight loss, decreased DAI and histopathological scores, decreased the expression levels of TLR2, MyD88, P-P65, P65 proteins, and TLR2 genes, and also suppressed the expression of inflammatory factors TNF-α, IL-1 β, and IL-6 in the peripheral blood of mice. ConclusionThe therapeutic effect of SH on DSS-induced UC in mice may be related to the inhibition of the TLR2/NF-κB signaling pathway.

Matrine Ameliorates DSS-Induced Colitis by Suppressing Inflammation, Modulating Oxidative Stress and Remodeling the Gut Microbiota.

Matrine (MT) possesses anti-inflammatory, anti-allergic and antioxidative properties. However, the impact and underlying mechanisms of matrine on colitis are unclear. The purpose of this research was to examine the protective impact and regulatory mechanism of matrine on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. MT alleviated DSS-induced UC by inhibiting weight loss, relieving colon shortening and reducing the disease activity index (DAI). Moreover, DSS-induced intestinal injury and the number of goblet cells were reversed by MT, as were alterations in the expression of zonula occludens-1 (ZO-1) and occludin in colon. Simultaneously, matrine not only effectively restored DSS-induced oxidative stress in colonic tissues but also reduced the production of inflammatory cytokines. Furthermore, MT could treat colitis mice by regulating the regulatory T cell (Treg)/T helper 17 (Th17) cell imbalance. We observed further evidence that MT alleviated the decrease in intestinal flora diversity, reduced the proportion of Firmicutes and Bacteroidetes, decreased the proportion of Proteobacteria and increased the relative abundance of Lactobacillus and Akkermansia in colitis mice. In conclusion, these results suggest that MT may mitigate DSS-induced colitis by enhancing the colon barrier integrity, reducing the Treg/Th17 cell imbalance, inhibiting intestinal inflammation, modulating oxidative stress and regulating the gut microbiota. These findings provide strong evidence for the development and application of MT as a dietary treatment for UC.

Brassinin alleviates cancer cachexia by suppressing diverse inflammatory mechanisms in mice.

Cancer cachexia is a multifactorial condition that contributes to the death of about 20% of cancer patients. It has the potential to cause weight loss, reduction in muscle mass, and loss of fat tissue, significantly lowering the quality of life. Currently, there are no approved drugs for cancer cachexia. Here, we have explored the possible impact of brassinin (BSN) on cancer cachexia under in vitro and in vivo settings. After differentiation, C2C12 and 3T3-L1 cells were incubated with colorectal carcinoma cells conditioned media or BSN. For preclinical studies, mice were injected with HT-29 cells followed by intraperitoneal administration of BSN, and muscle and adipose tissues were evaluated by Western blotting and hematoxylin and eosin staining. BSN effectively suppressed muscle atrophy by down-regulating the levels of Muscle RING-finger protein-1 and Atrogin-1, while also increasing the expression of myosin heavy chain in cachexia-induced-C2C12 myotubes. The induction of adipogenesis by BSN prevented adipocyte atrophy in cachexia-induced 3T3-L1 adipocytes. We also noted that BSN disrupted the interaction between COX-2 and signaling transducer and activator of transcription 3 (STAT3) promoter, leading to down-regulation of STAT3 activation. Moreover, it was found that BSN inhibited weight loss in mice and demonstrated anti-cachexic effects. Overall, our observations indicate that BSN can attenuate cancer cachexia through diverse mechanisms.

Protective effect of cellulose and soluble dietary fiber from Saccharina japonica by-products on regulating inflammatory responses, gut microbiota, and SCFAs production in colitis mice

This study aimed to investigate the physicochemical properties of soluble dietary fiber (SDF) and cellulose enriched in Saccharina japonica by-products and to evaluate their anti-colitis effects. The water-holding capacity (WHC), swelling capacity (SC), cation exchange capacity (CEC), and antioxidant properties of SDF were superior to cellulose. The ΔH of SDF and cellulose was 340.73 J/g and 134.56 J/g, and the average particle size of them was 43.858 μm and 97.350 μm. The viscosity of SDF was positively correlated with the content. SEM revealed that the microstructure of SDF was porous, whereas cellulose was folded. SDF contained seven monosaccharides such as mannuronic acid and mannose, while cellulose had a single glucose composition. It was also shown that both SDF and cellulose reversed the pathological process of colitis by inhibiting weight loss, preventing colon injury, balancing oxidative stress, and regulating the level of inflammation, with the optimal dose being 1.5 g/kg. The difference was that SDF inhibited the expression of NF-кB and TNF-α, while cellulose up-regulated the expression of PPAR-γ and IL-10. Additionally, SDF could more positively control the expression of ZO-1, whereas cellulose was superior in improving the expression of Occludin. Interestingly, SDF could restore the structure of norank_f_Muribaculaceae and Lachnospiraceae_NK4A136_group to ameliorate ulcerative colitis (UC), whereas cellulose mainly regulated the abundance of norank_f_Muribaculaceae, Faecalibaculum, Bacteroides and unclassified_f__Lachnospiraceae. The production of short-chain fatty acids (SCFAs) was also found to be restored by SDF and cellulose. Overall, SDF and cellulose can be considered important dietary components for treating and preventing UC.

Individual and combined treatments of 2,4-epibrassinolide (EBR) and calcium chloride (CaCl2) maintain the postharvest quality of baby mustard

Baby mustard is a characteristic vegetable of the Southwest China, and its quality, including appearance quality and nutritional quality, deteriorated during the postharvest senescence process. This study investigated the effects of individual and combined treatments with 2,4-epibrassinolide (EBR) and calcium chloride (CaCl2) on the visual quality and health-promoting compounds of baby mustard stored at room temperature. In terms of appearance, individual treatments with EBR and CaCl2 were more effective than the control and combined treatment in sensory evaluation and weight loss inhibition. All three exogenous treatments maintained the content of pigments, especially individual treatments. The total chlorophyll content was 1.6-, 1.6-, and 1.1-fold higher in EBR-, CaCl2-, and EBR + CaCl2-treated samples than in control samples at 4 days, respectively. In terms of nutritional quality, all three exogenous treatments delayed the decrease in glucosinolates and soluble protein content, with EBR treatment being the most effective in preserving the content of indolic glucosinolates. Additionally, three exogenous treatments effectively maintained antioxidant levels, thereby reducing hydrogen peroxide accumulation. Combined treatment inhibited brassinosteroid signaling, revealing a potential antagonistic relationship between EBR and CaCl2. The results suggest that the three exogenous treatments delayed senescence and preserved the postharvest quality of baby mustard. EBR treatment was the most effective in preserving pigments. This experiment provides potential technical and theoretical basis for the postharvest preservation of baby mustard.

Postharvest quality and metabolism changes of daylily flower buds treated with hydrogen sulfide during storage

Daylily flower buds are a good source of nutrients and contain lots of bioactive compounds, but they are subject to deterioration after harvest, which limits the taste and consumer satisfaction. Hydrogen sulfide (H2S) has been regarded as an important gaseous signaling molecule, which could prolong postharvest freshness of fruits and vegetables. The present study aims to investigate the effects of H2S on postharvest quality and metabolism changes of daylily flower buds during storage. The results showed that 3.2 mM NaHS (H2S donor) effectively inhibited weight loss, blooming and decay of daylily during storage. H2S application markedly reduced the accumulation of malondialdehyde and H2O2. H2S treatment also delayed the loss of total protein and antioxidant glutathione, and maintained the activities of antioxidant enzymes superoxide dismutase and catalase at higher level compared to control group. Widely targeted metabolomics identified various differentially accumulated metabolites (DAMs) during storage and with H2S treatment of daylily. These DAMs largely distributed in the classes of amino acids, organic acids, sugars and alcohols, terpenoids. A special focus was given to 303 common DAMs between the comparison of CK0 vs. CK6 and CK6 vs. T6, of which the DAMs were mainly enriched in the KEGG pathways of monobactam biosynthesis, pyrimidine metabolism, glycine, serine and threonine metabolism, arginine biosynthesis, pentose and glucuronate interconversions. Four DAMs including Cytidine 5′-Monophosphate, Fumaric Acid, Hydroxypyruvic Acid, 2′-Deoxycytidine-5′-Monophosphoric Acid exhibited great downregulation during storage, and H2S treatment dramatically recovered their relative contents. This study indicated that H2S treatment offers the potential to preserve the quality of daylily flower buds and extend their postharvest life.

Antimicrobial photodynamic therapy with Brazilian green propolis controls intradermal infection induced by methicillin-resistant Staphylococcus aureus and modulates the inflammatory response in a murine model.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of skin and soft tissue infections worldwide. This microorganism has a wide range of antibiotics resistance, a fact that has made the treatment of infections caused by MRSA difficult. In this sense, antimicrobial photodynamic therapy (aPDT) with natural products has emerged as a good alternative in combating infections caused by antibiotic-resistant microorganisms. The objective of the present study was to evaluate the effects of aPDT with Brazilian green propolis against intradermal MRSA infection in a murine model. Initially, 24 Balb/c mice were infected intradermally in the ears with 1.5 × 108 colony-forming units of MRSA 43300. After infection, they were separated into 4 groups (6 animals per group) and treated with the vehicle, only Brazilian green propolis, only blue LED light or with the aPDT protocol (Brazilian green propolis + blue LED light). It was observed in this study that aPDT with Brazilian green propolis reduced the bacterial load at the site of infection. Furthermore, it was able to inhibit weight loss resulting from the infection, as well as modulate the inflammatory response through greater recruitment of polymorphonuclear cells/neutrophils to the infected tissue. Finally, aPDT induced an increase in the cytokines IL-17A and IL-12p70 in the draining retromaxillary lymph node. Thus, aPDT with Brazilian green propolis proved to be effective against intradermal MRSA infection in mice, reducing bacterial load and modulating the immune response in the animals. However, more studies are needed to assess whether such effects are repeated in humans.

Lacticaseibacillus paracasei JM053 alleviates osteoporosis in rats by increasing the content of soy isoflavone aglycones in fermented soymilk.

Lacticaseibacillus paracasei JM053 has a significant ability to convert soy isoflavones and can be used as a fermentation strain to ferment soymilk, thereby increasing the content of free aglycones in soymilk and thus providing an effective method to alleviate osteoporosis symptoms. This study aims to establish a rat model of osteoporosis induced by dexamethasone (DEX) and clarify the alleviating effect of soymilk fermented with Lacticaseibacillus paracasei JM053 on osteoporosis. Research has shown that fermented soymilk with Lacticaseibacillus paracasei JM053 can inhibit weight loss in rats caused by DEX, regulate the expression of inflammatory factors such as tumor necrosis factor-α (TNF-α) towards normal levels, and increase levels of alkaline phosphatase (ALP) and osteocalcin (OCN) to promote bone synthesis. By observing the microstructure of bone tissue through microCT and Goldner staining, it was found that, compared with the model group, fermented soymilk with Lacticaseibacillus paracasei JM053 can alleviate the damage to bone tissue structure caused by DEX by increasing the number of bone trabeculae and reducing fracture. Fermented soymilk with Lacticaseibacillus paracasei JM053 can alleviate bone metabolism disorders by regulating gut microbiota and metabolite content. This study provides theoretical and data-based support for developing functional products that can alleviate osteoporosis.

Therapeutic effect of total flavonoids of Sargentodoxa cuneata on ulcerative colitis in mice by correcting gut dysbiosis

Sargentodoxa cuneata is a traditional Chinese herb commonly used for the treatment of ulcerative colitis (UC) in clinical practice. However, the effects of total flavonoids of Sargentodoxa cuneata (TFSc) remain unclear. In this study, we explored the effects and mechanisms of action of TFSc in mice with dextran sulfate sodium-induced UC. The TFSc components were identified using liquid chromatography-tandem mass spectrometry. Mice with UC were orally administered TFSc to evaluate its effects on colon and liver damage. Changes in gut microbiota were analyzed using 16S rRNA gene sequencing. Moreover, the levels of short-chain fatty acids (SCFAs) and few organic acids in the intestinal contents were measured. Furthermore, the correlation amongst gut flora, SCFAs, and organic acids was studied. A total of 304 compounds were identified. TFSc alleviated the symptoms of UC in mice, inhibited weight loss, reduced the disease activity index, and improved colon shortening along with cardiac and hepatic indices. Furthermore, TFSc mitigated pathological changes in the colon and liver, and reduced the TNF-α levels in colon tissues of mice with UC. TFSc also modulated intestinal flora disorders, increased the levels of four SCFAs (isocaproic acid, 3-hydroxyisovaleric acid, isobutyric acid, and ethylmethylacetic acid), and decreased the levels of two organic acids (malonic acid and succinic acid). The differential regulation of SCFAs and organic acids by TFSc was strongly associated with specific gut flora. TFSc showed potential for improving colon and liver injury in mice with UC by regulating the intestinal flora and associated metabolites (SCFAs and organic acids). These findings provide new evidence for developing TFSc as a drug for treating UC and UC-related liver injuries.

Pan-antiviral effects of a PIKfyve inhibitor on respiratory virus infection in human nasal epithelium and mice.

Endocytosis, or internalization through endosomes, is a major cell entry mechanism used by respiratory viruses. Phosphoinositide 5-kinase (PIKfyve) is a critical enzyme for the synthesis of phosphatidylinositol (3, 5)biphosphate (PtdIns (3, 5)P2) and has been implicated in virus trafficking via the endocytic pathway. In fact, antiviral effects of PIKfyve inhibitors against SARS-CoV-2 and Ebola have been reported, but there is little evidence regarding other respiratory viruses. In this study, we demonstrated the antiviral effects of PIKfyve inhibitors on influenza virus and respiratory syncytial virus in vitro and in vivo. PIKfyve inhibitors Apilimod mesylate (AM) and YM201636 concentration-dependently inhibited several influenza strains in an MDCK cell-cytopathic assay. AM also reduced the viral load and cytokine release, while improving the cell integrity of human nasal air-liquid interface cultured epithelium infected with influenza PR8. In PR8-infected mice, AM (2 mg/mL), when intranasally treated, exhibited a significant reduction of viral load and inflammation and inhibited weight loss caused by influenza infection, with effects being similar to oral oseltamivir (10 mg/kg). In addition, AM demonstrated antiviral effects in RSV A2-infected human nasal epithelium in vitro and mouse in vivo, with an equivalent effect to that of ribavirin. AM also showed antiviral effects against human rhinovirus and seasonal coronavirus in vitro. Thus, PIKfyve is found to be involved in influenza and RSV infection, and PIKfyve inhibitor is a promising molecule for a pan-viral approach against respiratory viruses.

Limosilactobacillus fermentum HF06-derived paraprobiotic and postbiotic alleviate intestinal barrier damage and gut microbiota disruption in mice with ulcerative colitis.

Paraprobiotics and postbiotics have shown potential in the treatment of ulcerative colitis (UC). However, their in vivo application is still in its infancy and their mechanisms of action are not well understood. Here, we investigated the mitigation effects of Limosilactobacillus fermentum HF06-derived paraprobiotic (6-PA) and postbiotic (6-PS) on dextran sulfate sodium induced UC and the potential mechanisms. Results indicated that the administration of 6-PA and 6-PS resulted in the inhibition of weight loss and colon shortening in mice with UC. Furthermore, they led to a significant reduction in both fecal moisture content and the levels of proinflammatory cytokines and oxidative stress in the intestine of the mice. 6-PA and 6-PS treatment strengthened the intestinal mucosal barrier by dramatically upregulating the levels of zonula occludens-1 and occludin proteins. In addition, 6-PA and 6-PS restored intestinal dysbiosis by regulating abundances of certain bacteria, such as Bifidobacterium, Faecalibaculum, Muribaculaceae, Corynebacterium, Escherichia-Shigella and Clostridium_sensu_stricto_1, and regulated the level of short-chain fatty acids. These findings illustrated for the first time that L. fermentum HF06-derived paraprobiotic and postbiotic enhanced the intestinal barrier function, and restored gut microbiota alterations. © 2023 Society of Chemical Industry.

Construction of carboxymethyl chitosan/PVA/chitin nanowhiskers multicomponent film activated with Cotylelobium lanceolatum phenolics and in situ SeNP for enhanced packaging application

This work focused on the construction of bioactive packaging films based on carboxymethyl chitosan and poly(vinyl alcohol) (CMP) as polymeric matrix and fortified with chitin nanowhiskers, Cotylelobium lanceolatum phenolic extract (CL) and in situ synthesized nano selenium. Extensive morphological, microstructural, physical and mechanical analysis revealed that the nanofillers were well-dispersed and integrated into CMP matrix. Incorporation of the extract and nano selenium produced excellent UV blocking properties without seriously compromising the transparency of the composite (CMP/CNW/CLNS1) film. Moreover, blending of CMP with the filler materials significantly elevated (p < 0.05) the surface hydrophobicity (WCA by 35.4°), water barrier (by 53.86 %), tensile strength (from 29.35 to 33.09 MPa), elongation at break (from 64.28 to 96.48 %), and thermal properties of the resultant CMP/CNW/CLNS1 film, with concomitant reduction in water solubility and swellability. Furthermore, the CMP/CNW/CLNS films exhibited remarkable improvement in antioxidant properties. When used for packaging of peeled fresh garlic cloves, the CMP/CNW/CLNS1 film pouch, not the plain CMP or CMP/CNW film pouches, inhibited weight loss, oxidative browning, and the emergence of black mold on the packaged cloves. The developed CMP/CNW/CLNS1 film demonstrated enhanced capacity to safeguard the quality of packaged food and improved shelf life. Therefore, the present study suggests that incorporation of CNW/CLNS into carboxymethyl chitosan/PVA films is a suitable and facile strategy for the fabrication of films with improved mechanical, physico-chemical and functional properties with great potential for application as a sustainable active packaging material in the food industry.

Zingerone Alleviates Morphine Tolerance and Dependence in Mice by Reducing Oxidative Stress-Mediated NLRP3 Inflammasome Activation.

Morphine (MPH) is widely used for pain management; however, long-term MPH therapy results in antinociceptive tolerance and physical dependence, limiting its clinical use. Zingerone (ZIN) is a natural phenolic compound with neuroprotective effects. We investigated the effects of single and repeated doses of ZIN on MPH-induced tolerance, dependence, and underlying biochemical mechanisms. After a dose-response experiment, tolerance was developed to MPH (10mg/kg, i.p.) for seven days. In the single-dose study, ZIN was administered on day seven. In the repeated-dose study, ZIN was administered for seven days. Naloxone (5mg/kg, i.p., 120min after MPH) was injected to assess withdrawal signs on day seven. The levels of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), total thiol (TT), and glutathione peroxidase (GPx) were measured in the prefrontal cortex. The protein levels of interleukin-1 beta (IL-1β) and NLRP3-ASC-Caspase-1 axis were assessed by ELISA and Western blotting, respectively. Results showed that ZIN (100mg/kg) had no antinociceptive activity, and subsequent experiments were performed at this dose. Repeated ZIN reversed MPH antinociceptive tolerance, whereas single ZIN did not. Single and repeated ZIN attenuated naloxone-induced jumping. In addition, repeated ZIN significantly inhibited weight loss. Repeated ZIN suppressed the MPH-induced increase in TBARS, NO, IL-1β, NLRP3, ASC, and Caspase-1. It also inhibited MPH-induced TT and GPx reduction. In contrast, single ZIN had no effect. Findings suggest that ZIN reduces MPH-induced tolerance and dependence by suppressing oxidative stress and NLRP3 inflammasome activation. This study provides a novel therapeutic approach to reduce the side effects of MPH.