Immunogenicity and safety of a recombinant Omicron BA.4/5-Delta COVID-19 vaccine ZF2202-A in Chinese adults.

BACKGROUND: The Recombinant Omicron BA.4/5-Delta COVID-19 Vaccine (ZF2202-A) is primarily designed for the Delta and Omicron BA.4/5 variants. Our objective was to assess the safety and immunogenicity of ZF2202-A in Chinese adults. METHODS: A total of 450 participants aged ≥ 18 years, who had completed primary or booster vaccination with a COVID-19 vaccine more than 6 months prior, were enrolled in this randomized, double-blind, active-controlled trial. Participants in the study and control groups were administered one dose of ZF2202-A and ZF2001, respectively. Immunogenicity subgroups were established in each group. RESULTS: At 14 days after vaccination, the seroconversion rates of Omicron BA.4/5, BF.7, and XBB.1 in the ZF2022-A group were 67.7 %, 58.6 %, and 62.6 %, with geometric mean titers (GMTs) of neutralizing antibodies at 350.2, 491.8, and 49.5, respectively. The main adverse reactions (ARs) were vaccination site pain, pruritus, fatigue, and asthenia in both the ZF2022-A group and ZF2001 group. CONCLUSIONS: The novel bivalent vaccine ZF2202-A demonstrated satisfactory immunogenicity and safety against Omicron variants as booster dose in adults with prior vaccination of COVID-19 vaccines.

Identification of novel aminopyrimidine derivatives for the treatment of mutant NSCLC.

Starting from the binding mode of allosteric EGFR inhibitor JBJ-04-125-02 and the key pharmacophore of the third-generation EGFR inhibitors, we designed and synthesized a novel series of EGFR inhibitors, represented by (R)-N-(4-((2-aminopyrimidin-4-yl)amino)phenyl)-2-(5-(4-(4-methylpiperazin-1-yl)phenyl)-1-oxoisoindolin-2-yl)-2-phenylacetamide (6q). Docking study demonstrated that top compound 6q spanned orthosteric and allosteric sites of EGFR, and formed three key H-bonds with the residues Asp855, Lys745, and Met793 located in two sites. Biological evaluation indicated that compound 6q showed potential inhibitory activity against Ba/F3-EGFRL858R/T790M/C797S and Ba/F3-EGFRDel19/T790M/C797S cells, with IC50 values of 0.42 µM and 0.41 µM, respectively. Furthermore, compound 6q showed excellent activity against mutant NSCLC cell line NCI-H1975-EGFRL858R/T790M/C797S cells, with IC50 value of 0.82 µM which was superior to that of osimertinib (IC50 = 2.94 µM), JBJ-04-125-02 (IC50 = 3.66 µM), and coadministration of JBJ-04-125-02 and osimertinib (IC50 = 1.25 µM). Cell cycle arrest and cell apoptosis assay indicated that compound 6q could promote apoptosis of NCI-H1975-EGFRL858R/T790M/C797S cells at the concentration of 0.8 µM and no obvious cell cycle arrest was found.

Preparation of Self-microemulsion Solids of Kaempferia galanga (L.) Volatile Oil and Its Effect on Rats with Gastric Ulcer.

Kaempferia galanga volatile oil (KVO), the main effective component of the medicinal plant Kaempferia galanga L., possesses a variety of pharmacological activities such as anti-inflammatory, antioxidant, and anti-angiogenic activities and has therapeutic potential for gastric ulcer (GU). However, poor solubility as well as instability limits the clinical application of KVO. In this study, K. galanga volatile oil self-microemulsion solids (KVO-SSMEDDS) were prepared to improve its bioavailability and stability, and the therapeutic effects were evaluated in a rat model with GU. The ratio of oil phase, emulsifier, and co-emulsifier in the KVO-SMEDDS prescription were optimized by plotting the pseudo-ternary phase diagram with the star point design-response surface method. Based on the optimal prescription, self-microemulsifying drug delivery system (SMEDDS) was prepared as solid particles (S-SMEDDS). The prepared KVO-SSMEDDS had a rounded and non-adhesive appearance, formed an O/W emulsion after dissolution in water, and had a uniform particle size distribution with good stability and solubility. It was administered to GU model animals, and the results showed that a certain dose of KVO-SSMEDDS solution could increase the content of gastric mucosal protective factors PGE2, TGF-α, and EGF in gastric tissues and serum, and the expression of inflammatory factors IL-8 and TNF-α was downregulated. Meanwhile, the expression of the NF-κB/COX-2 pathway proteins was inhibited. In conclusion, the prepared KVO-SSMEDDS has good dispersion, solubility, and stability and has a therapeutic effect on rats with GU.

Rapamycin suppresses neuroinflammation and protects retinal ganglion cell loss after optic nerve crush.

Pyroptosis, an inflammasome-mediated mode of death, plays an important role in glaucoma. It has been shown that regulating the mTOR pathway can inhibit pyroptosis. Unfortunately, whether rapamycin (RAPA), a specific inhibitor of the mTOR pathway, can inhibit optic nerve crush (ONC)-induced pyroptosis to protect retinal ganglion cells (RGCs) has not been investigated. Our research aimed to confirm the effect of intravitreal injection of RAPA on RGCs. Furthermore, we used the ONC model to explore the underlying mechanisms. First, we observed that intravitreal injection of RAPA alleviated RGC damage induced by various types of injury. We then used the ONC model to further explore the potential mechanism of RAPA. Mechanistically, RAPA not only reduced the activation of glial cells in the retina but also inhibited retinal pyroptosis-induced expression of inflammatory factors such as nucleotide-binding oligomeric domain-like receptor 3 (NLRP3), apoptosis-associated speckle-like protein containing a CARD (ASC), N-terminal of gasdermin-D (GSDMD-N), IL-18 and IL-1ß. Moreover, RAPA exerted protective effects on RGC axons, possibly by inhibiting glial activation and regulating the mTOR/ROCK pathway. Therefore, this study demonstrates a novel mechanism by which RAPA protects against glaucoma and provides further evidence for its application in preclinical studies.

Comparison of Lycium barbarum fruits polysaccharide from different regions of China by acidic hydrolysate fingerprinting-based HILIC-ELSD-ESI-TOF-MS combined with chemometrics analysis.

INTRODUCTION: Lycium barbarum is an edible fruit widely used in herbal medicines and as a functional food. Polysaccharide is one of the most important active ingredients. Only L. barbarum grown in the Ningxia region of China are officially recognised as suitable for use in traditional Chinese medicine, but the systematic comparison of L. barbarum polysaccharide between Ningxia and the other growing regions of China has been rarely reported. OBJECTIVE: To compare the difference of L. barbarum polysaccharide from different grown regions of China. METHODS: A chemical fingerprint of L. barbarum polysaccharide hydrolysates was established based on controlled acidolysis combined with hydrophilic interaction liquid chromatography-evaporative light scattering detection-electrospray ionisation-time-of-flight-mass spectrometry (HILIC-ELSD-ESI-TOF-MS). Then, it was employed for the comparison of L. barbarum samples from different geographical origins of China combined with chemometrics analysis. RESULTS: Six monosaccharides [rhamnose (Rha), xylose (Xyl), arabinose (Ara), mannose (Man), glucose (Glu), galactose (Gal)] were qualitatively and quantitatively determined and four glycoconjugates were preliminarily identified from the hydrolysates. Content determination for the polysaccharide and monosaccharide indicated obvious geographical features. The HILIC-ELSD fingerprint combined with partial least squares-discriminant analysis (PLS-DA) was able to differentiate L. barbarum samples from Ningxia, Xinjiang, Gansu and Qinghai regions with 89.19% classification accuracy. Orthogonal projection to latent structure discriminant analysis (OPLS-DA) was able to differentiate between samples from Ningxia and those from the other three growing regions, polysaccharide and Ara were the potential chemical markers. CONCLUSIONS: These findings form the basis of a reliable method to trace the region of origin of L. barbarum sample and thereby, improve the quality control of L. barbarum therapeutic polysaccharides.

Efficacy and safety of unrestricted visiting policy for critically ill patients: a meta-analysis.

AIM: To compare the safety and effects of unrestricted visiting policies (UVPs) and restricted visiting policies (RVPs) in intensive care units (ICUs) with respect to outcomes related to delirium, infection, and mortality. METHODS: MEDLINE, Cochrane Library, Embase, Web of Science, CINAHL, CBMdisc, CNKI, Wanfang, and VIP database records generated from their inception to 22 January 2022 were searched. Randomized controlled trials and quasi-experimental studies were included. The main outcomes investigated were delirium, ICU-acquired infection, ICU mortality, and length of ICU stay. Two reviewers independently screened studies, extracted data, and assessed risks of bias. Random­effects and fixed-effects meta­analyses were conducted to obtain pooled estimates, due to heterogeneity. Meta-analyses were performed using RevMan 5.3 software. The results were analyzed using odds ratios (ORs), 95% confidence intervals (CIs), and standardized mean differences (SMDs). RESULTS: Eleven studies including a total of 3741 patients that compared UVPs and RVPs in ICUs were included in the analyses. Random effects modeling indicated that UVPs were associated with a reduced incidence of delirium (OR = 0.4, 95% CI 0.25-0.63, I2 = 71%, p = 0.0005). Fixed-effects modeling indicated that UVPs did not increase the incidences of ICU-acquired infections, including ventilator-associated pneumonia (OR = 0.96, 95% CI 0.71-1.30, I2 = 0%, p = 0.49), catheter-associated urinary tract infection (OR 0.97, 95% CI 0.52-1.80, I2 = 0%, p = 0.55), and catheter-related blood stream infection (OR = 1.15, 95% CI 0.72-1.84, I2 = 0%, p = 0.66), or ICU mortality (OR = 1.03, 95% CI 0.83-1.28, I2 = 49%, p = 0.12). Forest plotting indicated that UVPs could reduce the lengths of ICU stays (SMD = - 0.97, 95% CI - 1.61 to 0.32, p = 0.003). CONCLUSION: The current meta-analysis indicates that adopting a UVP may significantly reduce the incidence of delirium in ICU patients, without increasing the risks of ICU-acquired infection or mortality. Further large-scale, multicenter studies are needed to confirm these indications.

Lollipop-Inspired Multilayered Drug Delivery Hydrogel for Dual Effective, Long-Term, and NIR-Defined Glaucoma Treatment.

Glaucoma is an ophthalmic disease that is characterized by elevated intraocular pressure (IOP). Eye drops are the preferred choice to reduce IOP for the treatment of glaucoma. However, the bioavailability of eye drops is low (<5%). Their long-term frequent administration cannot ensure patient compliance, which is the main reason for treatment failure. Inspired by lollipop, herein, a multilayered sodium alginate-chitosan (SA-CS) hydrogel ball (HB) decorated by zinc oxide-modified biochar (ZnO-BC) is developed as a new drug delivery system. The multilayer structure encapsulate timolol maleate (TM) and levofloxacin inside the different layers to realize the sustained release of drugs, which can control ocular hypertension and prevent infection effectively. The results show that the release of TM can be sustained in vitro for longer than 2 weeks. Moreover, IOP is also effectively reduced in vivo. Meanwhile, the photothermal conversion activity of ZnO-BC can regulate drug release on demand after stimulation by near-infrared irradiation. More importantly, the designed HB also shows good biocompatibility and antibacterial properties in vitro and in vivo. In summary, ZnO-BC-SA-CS HB can effectively reduce IOP and is expected to replace the classical tedious eye drop strategy, having potential utilization value in the treatment of glaucoma.

Cinnamaldehyde Treatment of Prostate Cancer-Associated Fibroblasts Prevents Their Inhibitory Effect on T Cells Through Toll-Like Receptor 4.

INTRODUCTION: Cancer-associated fibroblasts (CAFs) promote tumor progression; thus, drugs that can modify CAFs need to be identified. METHODS: To test the effect of cinnamaldehyde on prostate CAFs, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-2H-tetrazolium bromide assay was used to determine their survival. When spleen cells were treated with CAF supernatant, the proliferation of T cells was inhibited as determined by flow cytometry. After cinnamaldehyde treatment, this immunosuppressive function of CAFs was partially reversed. To explore the molecular mechanism, Western blotting and the quantitative real-time polymerase chain reaction were applied, and TLR4-dependent signaling pathway-related protein and mRNA levels were quantified. RESULTS: Cinnamaldehyde acted on the TLR4-dependent signaling pathway, altering the function of CAFs such that its supernatant no longer inhibited the proliferation of T cells. CONCLUSION: These data indicate that cinnamaldehyde can modify the functions of CAFs, which may be helpful for treating tumors. Cinnamaldehyde can suppress CAF T-cell inhibition.

Beta-1,6 glucan converts tumor-associated macrophages into an M1-like phenotype.

Tumor-associated macrophages (TAMs) with an M2-like phenotype have been linked to immunosuppression and resistance to chemotherapies of cancer, thus targeting TAMs has been an attractive therapeutic strategy to cancer immunotherapy. We have reported that the ß-D-(1→6) glucan (AAMP-A70) isolated from Amillariella Mellea could promote macrophage activation. The present study showed that the ß-1,6-glucan could promote the transformation of M2-like macrophages to M1-like phenotype and inhibit the viability of colon cancer cells in vitro and in vivo. On a cellular mechanistic level, the ß-1,6-glucan reset tumor-promoting M2-like macrophages to tumor-inhibiting M1-like phenotype via increasing the phosphorylation of Akt/NF-κB and MAPK. Further, TLR2 was identified as the receptor of ß-1,6-glucan in the transformation effect. In addition, a very similar ß-1,6-glucan with side chains of ß-Glc or α-Galρ which was purified from Lentinus edodes showed same activities with those from Amillariella Mellea. Our findings shed light on the action mode of ß-1,6-glucan in cancer immunotherapy.

Topical administration of rapamycin promotes retinal ganglion cell survival and reduces intraocular pressure in a rat glaucoma model.

Glaucoma is a progressive optic neuropathy that has become the most common cause of irreversible blindness worldwide. Studies have shown that the protein mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a central role in regulating numerous functions, such as growth, proliferation, cytoskeletal organization, metabolism, and autophagy. Clinical trials have shown that Rho-associated protein kinase (ROCK) inhibitors reduced intraocular pressure (IOP) in patients with glaucoma and ocular hypertension (OHT). In this study, we explored whether rapamycin (RAPA) eye drops can reduce IOP and protect retinal ganglion cells (RGCs). Our results indicated that in rats treated with RAPA, the drug was detected in the aqueous humor (AH), and the IOP was reduced. This may be related to the inhibition of RhoA protein activation by RAPA and regulation of the actin cytoskeleton in trabecular meshwork (TM) cells. In addition, the retinal thickness and the survival rate of RGCs were significantly reduced in the OHT group compared with the control group. These changes in the OHT group were significantly improved after treatment with RAPA. This may be because RAPA inhibited the activation of glial cells and the release of proinflammatory factors, thereby attenuating further damage to the retina and RGCs. Taken together, the results of this study demonstrated that RAPA not only reduced IOP but also protected RGCs, suggesting that RAPA is likely to be an effective strategy for the treatment of glaucoma.

Acidic hydrolysate fingerprints based on HILIC-ELSD/MS combined with multivariate analysis for investigating the quality of Ganoderma lucidum polysaccharides.

In this preliminary study, the acidic hydrolysate fingerprints of polysaccharides based on hydrophilic-interaction chromatography-evaporative light scattering detection-electrospray time-of-flight mass spectrometry (HILIC-ELSD/ESI-TOF/MS) combined with multivariate statistical analysis was developed and applied to investigate the quality of Ganoderma lucidum from different regions. Projection-to-latent-structure discrimination analysis (PLS-DA) could distinguish samples of Zhejiang regions from those of other regions. Orthogonal-projection-to-latent-structure discrimination analysis (OPLS-DA) provided clear discrimination between G. lucidum samples cultivated in Zhejiang and that from other regions, in which Polysaccharides and D-galactose could be considered as candidate biomarkers. In addition, the intraspecific differentiation of G. lucidum was preliminarily investigated with samples from Shaanxi region. They were classified into four groups by PCA and PLS-DA, in which L-rhamnose, D-xylose, L-arabinose, and mannose were considered as potential chemical markers. These preliminary results contributed to our understanding of the variance of polysaccharides in Ganoderma spp. from different geographic origins and the intraspecific differentiation from the same region, which suggest great potential in the quality control of Ganoderma spp.

Spectrum-effect relationship between fingerprints and hemopoietic effects of small molecular fraction of Polygoni Multiflori radix praeparata.

Polygoni multiflori Radix Praeparata (PMRP) is a traditional medicine used for nourishing essence and blood in China. However, it is unclear which PMRP compounds are responsible for its hematopoietic effect. In this study, spectrum-effect relationship was used to discovery potential hematopoietic compounds. The fingerprints of 20 PMRP batches were established by HPLC and the hematopoietic effect was determined using red blood cell, hemoglobin, hematocrit, and platelet indexes in aplastic anemia model mice. The spectrum-effect relationship between common peaks and hematopoietic efficacy values was established using gray relational analysis and partial least squares analysis. Spectrum-effect relationship results showed that peaks 21 (emodin-8-O-(6´-O-acetyl)-ß-D-glucoside), 15 (2, 3, 5, 4'-tetrahydroxystilbene-2-O-di-glucoside), 16 (cis-2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside), 11 (unknown), 20(unknown, 12 (epicatechin), 29 (carboxyl emodin), and 31 (emodin) in the fingerprints were closely related to the hematopoietic effect. This work successfully established the spectrum-effect relationship between PMRP hematopoietic effect and its fingerprints, which can be used to explain the material basis for the PMRP hematopoietic effect.

Preparation of chondroitin sulfates with different molecular weights from bovine nasal cartilage and their antioxidant activities.

Biological functions of chondroitin sulfate, including anti-oxidation and anti-inflammation, are associated with its molecular weight. This study aimed to evaluate the correlation between antioxidant activity and molecular weights of chondroitin sulfate derived from bovine nasal cartilage (BCS). BCS extracted by compound enzymatic method was further purified via DEAE-cellulose column separation to obtain BCS-II (129.4 kDa), which was further degraded by H2O2-Vc to obtain four subfractions: BCS-II-1 (92.7 kDa), BCS-II-2 (54.1 kDa), BCS-II-3 (26.3 kDa), and BCS-II-4 (19.7 kDa). Changes in the physicochemical properties of BCS-II before and after degradation were compared via FT-IR, NMR and monosaccharide composition analysis. Finally, antioxidant activities of BCS-II and its subfractions BCS-II-1-4 were compared. Our results showed that the H2O2-Vc system did not disrupt the primary functional group of BCS-II, with no significant change in sulfate content between BCS-II and its degraded fractions; however, uronic acid levels increased in degraded fractions when compared with BCS-II. In vitro, BCS-II-4 displayed the lowest molecular weight and had the strongest antioxidant activity. Therefore, the antioxidant activity of chondroitin sulfate in vitro is robustly associated with its molecular weight, and low-molecular-weight chondroitin sulfate can be used as an antioxidant in the food and pharmaceutical industries and other sectors.

Ligustilide promotes apoptosis of cancer-associated fibroblasts via the TLR4 pathways.

The goal of this research was to study the selective pro-apoptotic effect of ligustilide on prostate-cancer-associated fibroblast in the tumor microenvironment and the related molecular mechanisms. The effects of ligustilide on cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs) isolated from the prostate were determined by MTT assay. Flow cytometry and cellular immunofluorescence were used to detect the effects of ligustilide on the cell cycle and apoptosis. Western blotting was used to detect the expression of apoptosis-related proteins after the action of ligustilide on CAFs. In the investigation, ligustilide had a selective pro-apoptotic effect on prostate-CAFs. After ligustilide treatment, the proportion of CAFs in the G2-M phase of the cell cycle increased, and the expression of apoptosis-related proteins (p-P53, Bcl-2, Caspase9 and Cytochrome C) changed. Ligustilide blocks the CAF cell cycle and induces the apoptosis of CAFs.

Hematopoietic effect of small molecular fraction of Polygoni multiflori Radix Praeparata in cyclophosphamide-induced anemia mice.

The aim of this study is to investigate the protective effects of a small molecular fraction (SMF) of Polygoni multiflori Radix Praeparata (PMRP) in a cyclophosphamide (CTX) induced anemia mouse model. Small molecular fraction of PMRP was prepared and identified by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). In pharmacology, we examined the peripheral hemogram and thymus and spleen index. The content of granulocyte-macrophage colony-stimulating factor (GM-CSF) in serum was mensurated by enzyme-linked immunosorbent assay (ELISA); The level of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) in serum and spleen tissue homogenate were detected, and glutathione peroxidase (GSH-PX) was assayed in spleen. The results show that SMF can significantly accelerate the recovery of peripheral hemogram, increase the activity of antioxidant enzymes and GM-CSF in serum and spleen. SMF also increases the number of spleen cells, improves bone marrow pathology. In conclusion, the SMF of PMRP promoted the recovery of hematopoietic function in a CTX-induced anemia mouse, which can support SMF to be used as an adjunct to chemotherapy to counteract its side effects.

Cinnamaldehyde causes apoptosis of myeloid-derived suppressor cells through the activation of TLR4.

Malignant tumors are among the most life-threatening diseases in the world. Although many different types of antitumor agents are available, severe side effects and toxicity limit their applications. Myeloid-derived suppressor cells (MDSCs) inhibit the antitumor immune response by suppressing the proliferation of T cells, the production of cytokines and the killing of tumor cells. As MDSCs have become novel targets in cancer therapy, this research focused on the anti-MDSC function of cinnamaldehyde (CA), which is extracted from cinnamon, a traditional Chinese spice. In the present study, MDSCs isolated from the spleens of mice with colon cancer were used as an in vitro model to assess the efficacy of CA. Treatment of MDSCs with CA significantly decreased cell proliferation and induced apoptotic cell death. Subsequent experiments demonstrated that CA treatment enhanced the expression of Bax and caspase-9 and inhibited the expression of Bcl-2, suggesting that CA induced apoptosis in the MDSCs via the intrinsic pathway. Taken together, the results demonstrated that CA exhibited significant anti-MDSC activity and attenuated the suppression of the antitumor immune response, indicating a potential use for CA in cancer therapy.

Lycium barbarum polysaccharides extend the mean lifespan of Drosophila melanogaster.

The fruits of Lycium barbarum are considered medicinal foods with high nutritional value and bioactivity. In this study, we aimed to evaluate the effect of a crude L. barbarum polysaccharide (LBP) and two derived fractions, LBP-1 and LBP-2, on the lifespan of Drosophila melanogaster (fruit fly). The average lifespan of fruit flies was extended by supplementing their diet with either of the three LBP preparations. In vivo analysis of antioxidant activities detected increased superoxide dismutase (SOD) and catalase (CAT) activities and decreased malondialdehyde (MDA) levels. Dietary LBP supplements significantly reduced the mortality rate of fruit flies induced by paraquat and hydrogen peroxide. Importantly, the strongest anti-aging activity was exhibited by the LBP-2 fraction, containing arabinogalactan with a molecular weight of 9 × 104 Da. Further studies showed that the anti-aging activity of LBP was, at least in part, mediated by an age-related signaling pathway (MAPK, TOR, S6K) and the expression of longevity genes (Hep, MTH, and Rpn11).

MPSSS impairs the immunosuppressive function of cancer-associated fibroblasts via the TLR4-NF-κB pathway.

The polysaccharides MPSSS was extracted from Lentinus edodes and has been reported to effectively inhibit tumor growth and eliminate the function of myeloid-derived immune suppressor cell-mediated T cell inhibition, thus improving the efficacy of cancer therapy. The exploration of how MPSSS affects the functions of cancer-associated fibroblasts (CAFs) will provide a new perspective for understanding the antitumor effects of MPSSS. In the present study, prostate CAFs were selected as target cells to study whether MPSSS affected cell proliferation and function. The results showed that MPSSS did not directly inhibit the growth of prostate CAFs but interfered with CAF-mediated T cell inhibition and affected the immunosuppressive function of prostate CAFs. Mechanistic studies were further performed and showed that MPSSS activated key node proteins in the NF-κB pathway that were dependent on MyD88, and a TLR4 inhibitor blocked the changes in these proteins and the effect of MPSSS. We hypothesize that MPSSS can activate the MyD88-dependent TLR4-NF-κB signaling pathway to change the function of CAFs. In conclusion, these results demonstrate that MPSSS can not only effectively inhibit the growth of prostate cancer as we previously reported but also alter the function of prostate CAFs by activating the TLR4-NF-κB pathway, providing a new strategy for the comprehensive treatment of tumors.

Supplementation with compound polysaccharides contributes to the development and metabolic activity of young rat intestinal microbiota.

Dietary intervention during early life has a significant impact on colonization of the gut microbiota. In addition, some polysaccharides have the potential to selectively stimulate the growth and metabolic activity of intestinal bacteria associated with health and well-being. However, less is known about the effect of polysaccharides on the development of gut microbiota in younger individuals. This study was conducted to investigate the health effects of supplementation with dietary compound polysaccharides (Lycium barbarum polysaccharides (LBP), Poria cocos polysaccharides (PCPs) and Lentinan, 1 : 1 : 1) on the intestinal microecosystem and metabolism of young rats. Male 21-day-old Sprague-Dawley rats received daily intragastric administration of either compound polysaccharides (three dosages, 6 g kg-1, 12 g kg-1 or 24 g kg-1) or saline for 28 consecutive days. 1H-NMR spectroscopy integrated with multi-variate pattern recognition analysis was applied to reveal the metabolism of the host and microflora, while 16S rRNA gene sequencing was used to monitor the dynamic changes in the gut microbiota. The relative concentrations of 35 urinary metabolites and 24 faecal metabolites were significantly changed compared with the control group. 16S rRNA analysis showed that the relative abundances of 4 bacterial genera (Bifidobacterium, Lactobacillus, Allobaculum and Oligella) significantly increased, whereas the relative abundance of 1 bacterial genus (Enterococcus) significantly declined in the compound polysaccharide-treated groups compared with the control group. Meanwhile, dietary compound polysaccharide treatment promoted the functional maturation of the gut bacterial community, characterised by increased basic metabolism (amino acid metabolism and energy metabolism), short chain fatty acid (SCFA)-related metabolism and nucleotide metabolism. These findings suggest that compound polysaccharides may help to promote the colonisation and functional maturation of infant intestinal microbiota and maintain the health of the intestinal microecosystem.