Epigallocatechin-3-gallate mitigates cadmium-induced intestinal damage through modulation of the microbiota-tryptophan-aryl hydrocarbon receptor pathway.

Early studies have shown that the gut microbiota is a critical target during cadmium exposure. The prebiotic activity of epigallocatechin-3-gallate (EGCG) plays an essential role in treating intestinal inflammation and damage. However, the exact intestinal barrier protection mechanism of EGCG against cadmium exposure remains unclear. In this experiment, four-week-old mice were exposed to cadmium (5 mg kg-1) for four weeks. Through 16 S rDNA analysis, we found that cadmium disrupted the gut microbiota and inhibited the indole metabolism pathway of tryptophan (TRP), which serves as the principal microbial production route for endogenous ligands to activate the aryl hydrocarbon receptor (AhR). Additionally, cadmium downregulated the intestinal AhR signaling pathway and harmed the intestinal barrier function. Treatment with EGCG (20 mg kg-1) and the AhR agonist 6-Formylindolo[3,2-b] carbazole (FICZ) (1 µg/d) significantly activated the AhR pathway and alleviated intestinal barrier injury. Notably, EGCG partially restored the gut microbiota and upregulated the TRP-indole metabolism pathway to increase the level of indole-related AhR agonists. Our findings demonstrate that cadmium dysregulates common gut microbiota to disrupt TRP metabolism, impairing the AhR signaling pathway and intestinal barrier. EGCG reduces cadmium-induced intestinal functional impairment by intervening in the intestinal microbiota to metabolize AhR agonists. This study offers insights into the toxic mechanisms of environmental cadmium and a potential mechanism to protect the intestinal barrier with EGCG.

Starvation induces hepatopancreas atrophy in Chinese mitten crab (Eriocheir sinensis) by inhibiting angiogenesis.

BACKGROUND: The hepatopancreas of crustaceans serves as a significant organ for both the synthesis and secretion of digestive enzymes, as well as energy storage. In the event of food shortage, the hepatopancreas can provide energy for survival. To investigate the potential regulatory mechanisms of the hepatopancreas in response to starvation in Eriocheir Sinensis, transcriptome analysis, histological study and qRT-PCR were performed. RESULTS: The results showed that starvation caused a decrease in the hepatopancreas index of E. sinensis, which had certain effects on the tissue structure, metabolism and angiogenesis in the hepatopancreas. In addition, WGCNA and linear regression analysis showed that the genes significantly related to the hepatopancreas index were mainly enriched in the angiogenesis pathway, in which AKT signaling played an important role. Starvation may inhibit AKT signaling pathway by reducing the expression of TGFBI, HSP27, HHEX, and EsPVF1, thereby hindering angiogenesis, promoting apoptosis, and leading to hepatopancreas atrophy. CONCLUSION: These results indicate that AKT plays an important role in the angiogenesis pathway and apoptosis of the starvation induced hepatopancreas index reduction, which is beneficial to further understand the effect of starvation stress on hepatopancreas of Chinese mitten crab.

Structural and pharmacological diversity of 1,4-naphthoquinone glycosides in recent 20 years.

1,4-naphthoquinones are the most widespread naphthoquinone compounds. Recently, many 1,4-naphthoquinone glycosides with different structural features have been obtained from both nature and synthesis, which has led to an increasing variety of naphthoquinone glycosides. In this paper, the structure variety and biological activity in recent 20 years are reviewed, and classified them according to the source and structure characteristics. Meanwhile the synthetic methods of O-, S-, C- and N-naphthoquinone glycosides and their structure activity relationships are also described. It was referred that the presence of polar groups of C2 and C5 and non-polar groups attached to C3 on the naphthoquinone ring are beneficial for their biological activities. It will provide more comprehensive literature resources for the future research of 1, 4-naphthoquinone glycosides and lay a theoretical foundation.

Research progress on the structure and biological diversities of 2-phenylindole derivatives in recent 20 years.

The privileged structure binds to multiple receptors with high affinity, which is helpful to the development of new bioactive compounds. Indole is classified as a privileged structure, which may be one of the most important structural categories in drug discovery. As a special subset of indole compounds, 2-phenylindole seems to be one of most promising forerunners of drug development. In this paper, 106 articles were referenced to review the structural changes, biological activities and structure-activity relationship of compounds in recent 20 years, and classified them according to their pharmacological activities, from several aspects, including anticancer, antibacterial, anti-inflammatory, analgesic, antiviral, anti-parasite, the biological activities target to central nervous system, et al. It also points out the importance of artificial intelligence (AI) technology in discovery of new 2-phenylindole compounds in a broader prospect. This review will provide some ideas for researchers to develop new indole drugs.

Synthesis of structurally diverse derivatives of aconitine-type diterpenoid alkaloids and their anti-proliferative effects on canine breast cancer cells.

As one of the most common malignancies in female dogs, no drugs have been developed specifically for the treatment of canine mammary carcinoma. In our previous study, a series of diterpenoid alkaloids derivatives were synthesized and exhibited good anti-proliferative activity in vitro against both normal and adriamycin-resistant human breast cancer cells lines. In this study, a series of structurally diverse aconitine-type alkaloids derivatives were also synthesized basing on the minimal modification principle, by modifying on A-ring, C-ring, D-ring, N-atom or salt formation on aconitine skeleton. Their anti-proliferative effects and mechanism on canine mammary cancer cells were investigated, exhibiting the importance of the substitution at A ring, the long chain ester at the C8, the hydroxyl group at the C13, the phenyl ring at the C14 and the N-ethyl group, while the methoxy group at the C1 and C16 showed little effect on the activity. The results of the proliferation, apoptosis and ultrastructure tests of the treated canine mammary carcinoma cells referred that the representative compound, aconitine linoleate (25) could block the cell cycle of canine mammary carcinoma cells in the G0/G1 phase, and exhibit the anti-proliferative effect by inducing apoptosis.

Cinnamaldehyde Restores Ceftriaxone Susceptibility against Multidrug-Resistant Salmonella.

In recent years, infections caused by multidrug-resistant (MDR) bacteria have greatly threatened human health and imposed a burden on global public health. To overcome this crisis, there is an urgent need to seek effective alternatives to single antibiotic therapy to circumvent drug resistance and prevent MDR bacteria. According to previous reports, cinnamaldehyde exerts antibacterial activity against drug-resistant Salmonella spp. This study was conducted to investigate whether cinnamaldehyde has a synergistic effect on antibiotics when used in combination, we found that cinnamaldehyde enhanced the antibacterial activity of ceftriaxone sodium against MDR Salmonella in vitro by significantly reduced the expression of extended-spectrum beta-lactamase, inhibiting the development of drug resistance under ceftriaxone selective pressure in vitro, damaging the cell membrane, and affecting its basic metabolism. In addition, it restored the activity of ceftriaxone sodium against MDR Salmonella in vivo and inhibited peritonitis caused by ceftriaxone resistant strain of Salmonella in mice. Collectively, these results revealed that cinnamaldehyde can be used as a novel ceftriaxone adjuvant to prevent and treat infections caused by MDR Salmonella, mitigating the possibility of producing further mutant strains.

Response surface methodology for optimization of the extraction of polysaccharide from the roots of onosma hookeri clarke. var. longiforum duthie and its antioxidant capacity and immune activity.

Onosma hookeri Clarke. var. longiforum Duthie (OHC-LD), one of the traditional Tibetan medicine, has been found many functions, including removing heat to cool blood, nourishing lung and inhibiting bacteria. In order to study the polysaccharides in OHC-LD water extract, the optimal extraction progress of polysaccharides of the roots of OHC-LD by response surface method designed with three-factor three-level Box-Behnken method and the antioxidant capacity and immune activity of the crude polysaccharide were studied in this investigation. Under the best conditions, the extraction yield of polysaccharide was 3.19±0.09% (n = 3). After purification, the crude polysaccharide was obtained with polysaccharide contents of 42.57%, which demonstrated stronger DPPH scavenging activity than BHT at low concentrations (<625 µg/mL), and comparable ABTS radical scavenging activity as BHT at high concentrations (≥1250 µg/mL). Additionally, it also exhibited a certain cell proliferation activity and an enhancement of the phagocytic ability of RAW264.7 cells. This study revealed that the crude polysaccharide from the roots of OHC-LD might be exploited as a natural antioxidant and immune enhance agent in the future in both medical and food industry.

Isolation, structure identification, and immunostimulatory effects in vitro and in vivo of polysaccharides from Onosma hookeri Clarke var. longiforum Duthie.

BACKGROUND: This study characterized an acidic polysaccharide (OHC-LDPA) isolated from the medicinal and edible homologous plant Onosma hookeri Clarke var. longiforum Duthie. The structure of OHC-LDPA was elucidated based on the analysis of infrared, one-/two-dimensional nuclear magnetic resonance, and gas chromatography-mass spectrometry data. The immunostimulatory effects of OHC-LDPA were identified by both in vitro and in vivo models. RESULTS: The structure of OHC-LDPA was elucidated as a typical pectin polysaccharide, consisting of galacturonic acid, galactose, arabinose, and rhamnose as the primary sugars, with linear galacturonic acid as the main chain and arabinogalacturonic acid as the main branched components. OHC-LDPA could significantly stimulate the proliferation and phagocytosis of RAW264.7 macrophages and the release of nitric oxide in vitro. Also, it could accelerate the recovery of spleen and thymus indexes, enhance the splenic lymphocyte proliferation responses, and restore the levels of interleukin-2, interleukin-10, interferon-γ, and immunoglobulin G in the serum in a cyclophosphamide-induced immunosuppressed-mice model. In addition, OHC-LDPA could restore the intestinal mucosal immunity and reduce the inflammatory damage. CONCLUSION: OHC-LDPA could improve the immunity both in vitro and in vivo and could be used as a potential immunostimulant agent. © 2022 Society of Chemical Industry.

A study of the antibacterial mechanism of pinocembrin against multidrug-resistant Aeromonas hydrophila.

Aeromonas hydrophila is a common pathogen in fish that has caused severe economic losses in aquaculture worldwide. With the emergence of bacterial resistance, it is necessary to develop new drugs to combat bacterial infection, particularly for multidrug-resistant bacteria. In this study, the antibacterial activity of pinocembrin was investigated by observing bacterial growth and microscopic structure, and its mechanism of action was identified by investigating its effect on protein and DNA. The antibacterial susceptibility test indicated that pinocembrin inhibits A. hydrophila growth. The minimal inhibitory concentration and minimum bactericidal concentration were 256 µg/mL and 512 µg/mL, respectively. Ultrastructurally, the bacteria treated with pinocembrin showed surface roughness and plasmolysis. When bacteria were treated with 512 µg/mL pinocembrin, lactate dehydrogenase activity and soluble protein content decreased significantly, and electrical conductivity and DNA exosmosis levels increased by 4.21 ± 0.64% and 15.98 ± 1.93 mg/L, respectively. Staining with 4', 6-Diamidino-2-phenylindole showed that the nucleic acid fluorescence intensity and density decreased after the treatment with pinocembrin. Pinocembrin may inhibit the growth of A. hydrophila by increasing cell membrane permeability and affecting protein and DNA metabolism. Thus, pinocembrin is a candidate drug for the treatment of A. hydrophila infection in aquaculture.

cMOS enhanced the mucosal immune function of skin and gill of goldfish (Carassius auratus Linnaeus) to improve the resistance to Ichthyophthirius multifiliis infection.

METHODS: of supporting mucosal immune barrier integrity and prevention of some pathogenic infections in aquatic species, are key areas of active study, often focusing on feed additives. The objectives of this study were to explore the effects of feeding cMOS (concentrated mannan oligosaccharide) on the gill and skin mucosal barriers of goldfish (Carassius auratus Linnaeus) and evaluate health status during Ichthyophthirius multifiliis infection. After feeding the cMOS-containing diet for 60 days, Hematoxylin and eosin (H&E) staining showed greater length of gill lamella and thicker dermal dense layer, while Alcian Blue and Periodic acid-Schiff (AB-PAS) staining showed higher numbers of mucin cells in cMOS fed fish. Chemical analysis showed that fish fed cMOS had greater enzyme activity of lysozyme (LZM) and alkaline phosphatase (AKP) in gill and skin tissues, while qRT-PCR revealed higher expression of Muc-2 and IL-1ß, as well as lower expression of IL-10. After Ichthyophthirius multifiliis challenge, goldfish fed the cMOS diet had lower mortality and infection rates, as well as fewer visible white spots on the body surfaces. Histologically, the gill and skin of these fish presented less tissue damage and fewer parasites, and had a greater number of mucus cells. In addition, the expression of Muc-2 and IL-10 were notably higher while the expression of IL-1ß was significantly lower in cMOS fed goldfish than control fed fish. In this study, cMOS fed goldfish had stronger immune barrier function of skin and gill mucous, and better survival following Ichthyophthirius multifiliis infection.

Cinnamaldehyde Resist Salmonella Typhimurium Adhesion by Inhibiting Type I Fimbriae.

Salmonella Typhimurium (S. Typhimurium), a common foodborne pathogen, severely harms the public and food security. Type I fimbriae (T1F) of S. Typhimurium, plays a crucial role in the pathogenic processes; it mediates the adhesion of bacteria to the mannose receptor on the host cell, assists the bacteria to invade the host cell, and triggers an inflammatory response. Cinnamaldehyde is the main ingredient in cinnamon essential oil. In this study, cinnamaldehyde was demonstrated to inhibit the expression of T1F by hemagglutination inhibition test, transmission electron microscopy, and biofilms. The mechanism of cinnamaldehyde action was studied by proteomics technology, PCR and Western blotting. The results showed that cinnamaldehyde can inhibit T1F in S. typhimurium without the growth of bacteria, by regulating the level of expression and transcription of fimA, fimZ, fimY, fimH and fimW. Proteomics results showed that cinnamaldehyde downregulated the subunits and regulators of T1F. In addition, the invasion assays proved that cinnamaldehyde can indeed reduce the ability of S. typhimurium to adhere to cells. The results of animal experiments showed that the colonization in the intestinal tract and the expression levels of inflammatory cytokine were significantly decreased, and the intestinal mucosal immune factors MUC1 and MUC2 were increased under cinnamaldehyde treatment. Therefore, cinnamaldehyde may be a potential drug to target T1F to treat Salmonella infections.

The synthesis review of the approved tyrosine kinase inhibitors for anticancer therapy in 2015-2020.

In the 21st century, cancer is the major public health problem worldwide. Based on the important roles of protein tyrosine kinase, the accelerated hunt for potent small-molecule tyrosine kinase inhibitors has led to the success of 30 newly inhibitors in this family for the cancer therapy in last five years. In this review, we updated their synthesis methods, and compared the original research routes with the optimized routes for each PTK inhibitor against different target, in order to make an outlook on the future synthesis of potential PTK inhibitors for anticancer therapy.

Synthesis and structure-activity relationship of lipo-diterpenoid alkaloids with potential target of topoisomerase IIα for breast cancer treatment.

Aconitine linoleate (11) isolated from the Aconitum sinchiangense W. T. Wang exhibited significant anti-tumor activity. Based on this, a series of novel lipo-diterpenoid alkaloids were synthesized and evaluated for their anticancer activities against MCF-7 and MCF-7/ADR cell lines. Seventeen compounds, including 18-20, 22, 24-32, 36, 39, 41-42 possessed higher anti-proliferative activities (IC50 < 20 µM) against MCF-7 cell lines, which were better than the reference drug etoposide (IC50 = 18.01 ± 1.64 µM), among which compound 24 (IC50 = 4.00 ± 0.30 µM) was found to be the most potent derivative, being 4.5-fold more active than etoposide. Meanwhile, eighteen compounds, including 18-22, 24, 26-32, 36, 38-39, 41-42 presented excellent activities (IC50 < 20 µM) against MCF-7/ADR cell lines, better than etoposide (IC50 = 35.48 ± 0.29 µM) and doxorubicin (IC50 = 67.61 ± 6.5 µM). The most potent compound (19) was 13.5- and 25.7-fold more active than etoposide and doxorubicin against MCF-7/ADR cell lines, respectively. The structure-activity relationship (SAR) studies indicated that the 3-OH, 8-lipo, 14-benzene ring, and nitrogen atom with proper alkaline are crucial elements for anti-proliferative activity of target lipo-diterpenoid compounds. The proper length, the double bonds or di-fluoro-substituted at C-8 fatty acid chain, the para-donating electron group on 14-benzene group, and 13-OH are all favorable for the enhancement of anti-proliferative activities. In conclusion, the introduction of the 8-lipo group into aconitine leads to significant increase of anti-proliferative activity against MCF-7 and MCF-7/ADR cells, which suggests these kinds of lipo-alkaloids are powerful and promising antitumor compounds for breast cancer, especially for drug-resistant breast cancer.

Antimicrobial resistance and genotyping of Staphylococcus aureus obtained from food animals in Sichuan Province, China.

BACKGROUND: Staphylococcus aureus (S. aureus), especially methicillin-resistant Staphylococcus aureus (MRSA), is considered a common zoonotic pathogen, causing severe infections. The objective of this study was to investigate the antimicrobial susceptibility, resistance genes and molecular epidemiology among MRSA and methicillin-susceptible Staphylococcus aureus (MSSA) isolated from food animals in Sichuan Province, China. METHODS: This study was conducted on 236 S. aureus isolates. All isolates were subjected to antimicrobial susceptibility testing by using a standard microbroth dilution method. The Polymerase Chain Reaction (PCR) was performed to identify genes encoding the ß-lactams resistance (blaZ, mecA), macrolides (ermA, ermB, ermC) and aminoglycosides (aacA-aphD). The molecular structures and genomic relatedness of MRSA isolates were determined by staphylococcal chromosome cassette mec (SCCmec) typing and pulsed-field gel electrophoresis (PFGE), respectively. RESULTS: Among 236 isolates, 24 (10.17 %) were recognized as MRSA. MRSA isolates showed different resistance rates to 11 antimicrobials ranging from 33.33 to 100 %, while for MSSA isolates the rates varied from 8.02 to 91.51 %. Multi-drug resistance phenotype was found in all MRSA isolates. The ermC gene encoding macrolides-lincosamides-streptogramin B was the most prevalent gene detected in 87.29 % of the S. aureus isolates, followed by ermB (83.05 %), blaZ (63.98 %), aacA-aphD (44.07 %), ermA (11.44 %) and mecA (11.02 %) genes. The prevalence of resistance genes in MRSA isolates was significantly higher than that of MSSA. Regarding the molecular morphology, SCCmec III (12/24, 50 %) was the most common SCCmec type. Furthermore, the PFGE typing showed that 24 MRSA were divided into 15 cluster groups (A to O), the major pulsotype J encompassed 25 % of MRSA isolates. CONCLUSIONS: The S. aureus isolates from food animals in Sichuan province of China have severe antimicrobials resistance with various resistance genes, especially MRSA isolates. Additionally, the genetic pool of MRSA isolates is diverse and complex, and further investigation is necessary.

The antiviral activity of kaempferol against pseudorabies virus in mice.

BACKGROUND: Pseudorabies virus (PRV), a member of the Alphaherpesviruses, is one of the most important pathogens that harm the global pig industry. Accumulated evidence indicated that PRV could infect humans under certain circumstances, inducing severe clinical symptoms such as acute human encephalitis. Currently, there are no antiviral drugs to treat PRV infections, and vaccines available only for swine could not provide full protection. Thus, new control measures are urgently needed. RESULTS: In the present study, kaempferol exhibited anti-PRV activity in mice through improving survival rate by 22.22 %, which was higher than acyclovir (Positive control) with the survival rate of 16.67 % at 6 days post infection (dpi); meanwhile, the survival rate was 0 % at 6 dpi in the infected-untreated group. Kaempferol could inhibit the virus replication in the brain, lung, kidney, heart and spleen, especially the viral gene copies were reduced by over 700-fold in the brain, which was further confirmed by immunohistochemical examination. The pathogenic changes induced by PRV infection in these organs were also alleviated. The transcription of the only immediate-early gene IE180 in the brain was significantly inhibited by kaempferol, leading to the decreased transcriptional levels of the early genes (EPO and TK). The expression of latency-associated transcript (LAT) was also inhibited in the brain, which suggested that kaempferol could inhibit PRV latency. Kaempferol-treatment could induce higher levels of IL-1ß, IL-4, IL-6, TNF-α and IFN-γ in the serum at 3 dpi which were then declined to normal levels at 5 dpi. CONCLUSIONS: These results suggested that kaempferol was expected to be a new alternative control measure for PRV infection.

Evaluation of pathology and environmental variables contributing to hepatopancreatic necrosis syndrome of Chinese mitten crab, Eriocheir sinensis.

Hepatopancreatic Necrosis Syndrome (HPNS) severely impacts the Chinese mitten crab (Eriocheir sinensis) industry. However, little knowledge of the aetiology and pathogenesis of the disease causes significant difficulties in its prevention and control. In this study, we conducted a pathological analysis of HPNS through time-integrated large-volume sampling, to clarify the disease characteristics and mechanism of HPNS-afflicted crabs; besides, animal models were constructed to verify the pathological diagnosis. The results showed that the hepatopancreas was the principal target organ of HPNS; multiple correspondence analysis revealed that the main histopathological characteristics included non-interstitial atrophic hepatopathy diseases such as hepatic tubule atrophy, dilated hepatic tubules, and hepatic tubule necrosis. Additionally, the muscles also showed signs of disease, including myofibre atrophy, necrosis, and inflammation. Ultrastructural studies showed prominent apoptosis and autophagy-like alterations in the hepatopancreas of HPNS-afflicted crabs. Further, the establishment of animal models revealed that the double variate stimulation of environmental variables such as abamectin/sewage with nutrition deficiency could result in HPNS-similar lesions. Based on these studies, we concluded that HPNS is a chronic hepatopancreas-initiated energy-consumed disease with a low likelihood of pathogen but a high probability of environment and nutrition.

Microbial analysis reveals the potential colonization of pathogens in the intestine of crayfish (Procambarus clarkii) in traditional aquaculture environments.

The microbiota of the intestine produces a wide array of biologically active molecules and together act as a composite endocrine organ. Due to our limited understanding of bacterial communities in aquaculture ecosystems, it is necessary to evaluate the interactions between environmental and intestinal microbiota and the potential consequences of disease. This study taken the traditional P. clarkii culture in the Sichuan Basin as an example, and analyzed the relationships between the microbiota of the environment and host through microbial analysis and microbiological diagnosis. Our results showed that the bacterial abundance in sediment was greater than in water, followed by the intestine, and some of bacteria from the environment successfully selected to colonize the intestine. The bacterial composition in the intestines of diseased and healthy crayfish was significantly different. The bacteria that colonized and proliferated in the intestine had very low abundances in sediment and water. Two potential pathogens, Aeromonas veronii, and Citrobacter freundii, and two potential probiotics, Lactococcus garvieae and Exiguobacterium undae, were identified. Using multiple, real, and traditional P. clarkii aquaculture sites in the Sichuan Basin, this study revealed that the microbial communities of the environment and animal host did indeed interact. Furthermore, these results indicated that P. clarkii in a healthy status are capable of regulating which bacteria colonize their intestines.

Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway.

Senescence in mesenchymal stem cells (MSCs) not only hinders the application of MSCs in regenerative medicine but is also closely correlated with biological aging and the development of degenerative diseases. In this study, we investigated the anti-aging effects of curcumin (Cur) on canine bone marrow-derived MSCs (cBMSCs), and further elucidated the potential mechanism of action based on the modulation of autophagy. cBMSCs were expanded in vitro with standard procedures to construct a cell model of premature senescence. Our evidence indicates that compared with the third passage of cBMSCs, many typical senescence-associated phenotypes were observed in the sixth passage of cBMSCs. Cur treatment can improve cBMSC survival and retard cBMSC senescence according to observations that Cur (1 µM) treatment can improve the colony-forming unit-fibroblasts (CFU-Fs) efficiency and upregulated the mRNA expression of pluripotent transcription factors (SOX-2 and Nanog), as well as inhibiting the senescence-associated beta-galactosidase (SA-ß-gal) activities and mRNA expression of the senescence-related markers (p16 and p21) and pro-inflammatory molecules (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)). Furthermore, Cur (0.1 µM~10 µM) was observed to increase autophagic activity, as identified by upregulation of microtubule-associated protein 1 light chain 3 (LC3), unc51-like autophagy-activating kinase-1 (ULK1), autophagy-related gene (Atg) 7 and Atg12, and the generation of type II of light chain 3 (LC3-II), thereby increasing autophagic vacuoles and acidic vesicular organelles, as well as causing a significant decrease in the p62 protein level. Moreover, the autophagy activator rapamycin (RAP) and Cur were found to partially ameliorate the senescent features of cBMSCs, while the autophagy inhibitor 3-methyladenine (3-MA) was shown to aggravate cBMSCs senescence and Cur treatment was able to restore the suppressed autophagy and counteract 3-MA-induced cBMSC senescence. Hence, our study highlights the important role of Cur-induced autophagy and its effects for ameliorating cBMSC senescence and provides new insight for delaying senescence and improving the therapeutic potential of MSCs.

Characterization of inulin-type fructans from two species of Radix Codonopsis and their oxidative defense activation and prebiotic activities.

BACKGROUND: Codonopsis pilosula and C. tangshen are both plants widely used in traditional Chinese medicine. Polysaccharides, which are their primary active components, are thought to be important in their extensive use. In this study, two neutral polysaccharide fractions of C. pilosula (CPPN) and C. tangshen (CTPN) were obtained by fractionation on a DEAE-Sepharose column and characterized. RESULTS: It was confirmed that the neutral polymers CPPN and CTPN were ß-(2,1)-linked inulin-type fructans with non-reducing terminal glucose, and degree of polymerization (DP) of 19.6 and 25.2, respectively. The antioxidant and prebiotic activities in vitro were assayed based on IPEC-J2 cell lines and five strains of Lactobacillus. Results indicated that the effects of CPPN and CTPN were increased antioxidant defense in intestinal epithelial cells through enhanced cell viability, improved expression of total antioxidant capacity, glutathione peroxidase, superoxide dismutase and catalase, and reduced levels of malondialdehyde and lactic dehydrogenase. The prebiotic activity of CPPN and CTPN was demonstrated by the promoting effect on Lactobacillus proliferation in vitro. The different biological activities obtained between the two fractions are probably due to the different DP and thus molecular weights of CPPN and CTPN. CONCLUSION: The inulin fractions from C. pilosula and C. tangshen were natural sources of potential intestinal antioxidants as well as prebiotics, which will be valuable in further studies and new applications of inulin-containing health products. © 2020 Society of Chemical Industry.

Study the antibacterial mechanism of cinnamaldehyde against drug-resistant Aeromonas hydrophila in vitro.

Aeromonas hydrophila, a highly infectious pathogen, causes several infections in aquatic animals and huge economic losses. Antibiotics are often used to treat A. hydrophila infections. However, overuse and irrational usage of antibiotics has led to severe antibiotic residues and emergence of resistance. There is therefore an urgent need for a new sustainable drug to control bacterial infection. Cinnamaldehyde, a plant-derived ingredient, has been found to have good antibacterial activity against A. hydrophila in vitro, but its mechanism of action remains unknown. In this study, we investigated the mechanism of cinnamaldehyde against A. hydrophila by evaluating the effects of cinnamaldehyde on A. hydrophila cell growth, cell morphology, electrical conductivity, lactate dehydrogenase (LDH), protein metabolism and DNA. The minimal inhibitory concentration and minimum bactericidal concentration of cinnamaldehyde were 256 and 512 µg/mL, respectively. Microscopy results showed disrupted cell wall and membrane, loss of cytoplasm, interior cavitation and unusual binary fission in the cinnamaldehyde-treated group. Electrical conductivity, LDH activity content and DNA extravasation in cinnamaldehyde-treated A. hydrophila increased by 7.14%, 16.75% and 20.29 µg/mL, respectively. Furthermore, nucleic acid fluorescence intensity and density decreased over time in the cinnamaldehyde-treated group. Taken together, these findings suggest that cinnamaldehyde can inhibit the growth of A. hydrophila by disrupting cell membranes and affecting protein metabolism.