Splenic Pseudoprogression After CAR-T Therapy Detected by 18 F-FDG PET/CT in a Refractory Diffuse Large B-Cell Lymphoma Patient.

ABSTRACT: A 43-year-old woman diagnosed with refractory diffuse large B-cell lymphoma was referred to chimeric antigen receptor T-cell therapy at our institution. After 3 cycles of bridging therapy, preinfusion 18 F-FDG PET/CT suggested a complete metabolic response. 18 F-FDG PET/CT 1 month after chimeric antigen receptor T-cell infusion showed 2 foci of elevated activity in the spleen, which was finally confirmed as pseudoprogression.

TRIM27-Induced Protective Autophagy: A Novel Therapeutic Approach for Pneumonia.

BACKGROUND: Pneumonia is a prevalent respiratory ailment involving complex physiological and pathological mechanisms. The tripartite motif containing 27 (TRIM27) plays a crucial role in regulating inflammation mechanisms. Therefore, the purpose of this study is to further explore the therapeutic potential of TRIM27 in pneumonia, based on its regulatory mechanisms in inflammation and autophagy. METHODS: This study established a mouse pneumonia animal model through lipopolysaccharide (LPS) administration, designating it as the LPS model group. Subsequently, adenovirus-mediated TRIM27 overexpression was implemented in the animals of the LPS model group, creating the TRIM27 treatment group. After a 7-day treatment period, lung tissues from the mice were collected. Various techniques, including immunohistochemistry, quantitative reverse transcription PCR (RT-qPCR), western blot, enzyme-linked immunosorbent assay (ELISA), and electron microscopy were utilized to analyze the impact of TRIM27 overexpression on inflammatory factors, oxidative stress, autophagy, and inflammatory processes in pulmonary tissues. Finally, an in vitro LPS cell model was established, and the effects of TRIM27 overexpression and autophagy inhibition on inflammatory cytokines and autophagosomes in LPS-induced inflammatory cells were examined through RT-qPCR and immunofluorescence techniques. RESULTS: The research findings demonstrate a significant reduction in the elevated levels of interleukin-6 (IL-6), IL-1ß, and Tumor necrosis factor-alpha (TNF-α) induced by LPS with TRIM27 overexpression (p < 0.01). Conversely, the autophagy inhibitor 3-Methyladenine (3-MA) diminished the effects induced by TRIM27 overexpression. Moreover, TRIM27 overexpression enhanced the expression of Microtubule-associated protein 1A/1B light chain 3 (LC3) II/I and Beclin-1 proteins in mice subjected to LPS stimulation (p < 0.01), while reducing the expression of the p62 protein (p < 0.01). The addition of 3-MA, however, decreased Beclin-1 expression and inhibited autophagy (p < 0.01). Additionally, TRIM27 overexpression decreased the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cleaved caspase-1, IL-1ß, and Gasdermin D N-terminal fragment (GSDMD-N) proteins in LPS-stimulated mice (p < 0.05). TRIM27 overexpression also decreased the levels of malondialdehyde (MDA), Activating Transcription Factor 6 (ATF6), and C/EBP-homologous protein (CHOP), while increasing the levels of superoxide dismutase (SOD) and glutathione (GSH) in mice exposed to LPS (p < 0.01). CONCLUSION: The induction of TRIM27 overexpression emerges as a potential and effective pneumonia treatment. The underlying mechanism may involve inducing protective autophagy, thereby reducing oxidative stress and cell pyroptosis.

The interaction of ER stress and autophagy in trophoblasts: navigating pregnancy outcome.

The endoplasmic reticulum (ER) is a complex and dynamic organelle that initiates unfolded protein response (UPR) and endoplasmic reticulum stress (ER Stress) in response to the accumulation of unfolded or misfolded proteins within its lumen. Autophagy is a paramount intracellular degradation system that facilitates the transportation of proteins, cytoplasmic components, and organelles to lysosomes for degradation and recycling. Preeclampsia (PE) and intrauterine growth retardation (IUGR) are two common complications of pregnancy associated with abnormal trophoblast differentiation and placental dysfunctions and have a major impact on fetal development and maternal health. The intricate interplay between ER Stress, and autophagy and their impact on pregnancy outcomes, through mediating trophoblast differentiation and placental development, has been highlighted in various reports. Autophagy controls trophoblast regulation through a variety of gene expressions and signalling pathways while excessive ER Stress triggers downstream apoptotic signalling, culminating in trophoblast apoptosis. This comprehensive review delves into the intricacies of placental development and explores the underlying mechanisms of PE and IUGR. In addition, this review will elucidate the molecular mechanisms of ER Stress and autophagy, both individually and in their interplay, in mediating placental development and trophoblast differentiation, particularly highlighting their roles in PE and IUGR development. This research seeks to the interplay between ER Stress and impaired autophagy in the placental trophoderm, offering novel insights into their contribution to pregnancy complications.

Gut microbiota contributes to bisphenol A-induced maternal intestinal and placental apoptosis, oxidative stress, and fetal growth restriction in pregnant ewe model by regulating gut-placental axis.

BACKGROUND: Bisphenol A (BPA) is an environmental contaminant with endocrine-disrupting properties that induce fetal growth restriction (FGR). Previous studies on pregnant ewes revealed that BPA exposure causes placental apoptosis and oxidative stress (OS) and decreases placental efficiency, consequently leading to FGR. Nonetheless, the response of gut microbiota to BPA exposure and its role in aggravating BPA-mediated apoptosis, autophagy, mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and OS of the maternal placenta and intestine are unclear in an ovine model of gestation. RESULTS: Two pregnant ewe groups (n = 8/group) were given either a subcutaneous (sc) injection of corn oil (CON group) or BPA (5 mg/kg/day) dissolved in corn oil (BPA group) once daily, from day 40 to day 110 of gestation. The maternal colonic digesta and the ileum and placental tissue samples were collected to measure the biomarkers of autophagy, apoptosis, mitochondrial dysfunction, ERS, and OS. To investigate the link between gut microbiota and the BPA-induced FGR in pregnant ewes, gut microbiota transplantation (GMT) was conducted in two pregnant mice groups (n = 10/group) from day 0 to day 18 of gestation after removing their intestinal microbiota by antibiotics. The results indicated that BPA aggravates apoptosis, ERS and autophagy, mitochondrial function injury of the placenta and ileum, and gut microbiota dysbiosis in pregnant ewes. GMT indicated that BPA-induced ERS, autophagy, and apoptosis in the ileum and placenta are attributed to gut microbiota dysbiosis resulting from BPA exposure. CONCLUSIONS: Our findings indicate the underlying role of gut microbiota dysbiosis and gut-placental axis behind the BPA-mediated maternal intestinal and placental apoptosis, OS, and FGR. The findings further provide novel insights into modulating the balance of gut microbiota through medication or probiotics, functioning via the gut-placental axis, to alleviate gut-derived placental impairment or FGR. Video Abstract.

Dietary rumen-protected L-arginine or N-carbamylglutamate enhances placental amino acid transport and suppresses angiogenesis and steroid anabolism in underfed pregnant ewes.

This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to 110 of gestation with either rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) on placental amino acid (AA) transport, angiogenic gene expression, and steroid anabolism. On d 35 of gestation, 32 Hu ewes carrying twin fetuses were randomly divided into four treatment groups, each consisting of eight ewes, and were fed the following diets: A diet providing 100% of NRC's nutrient requirements for pregnant ewes (CON); A diet providing 50% of NRC's nutrient requirements for pregnant ewes (RES); RES diet plus 5 g/d NCG (RES + NCG); or RES diet plus 20 g/d RP-Arg (RES + ARG). On the d 110 of pregnancy, blood samples were taken from the mother, and samples were collected from type A cotyledons (COT; the fetal portions of the placenta). The levels of 17ß-estradiol and progesterone in the maternal serum and both the capillary area density (CAD) and capillary surface density (CSD) in type A COT were decreased in response to Arg or NCG supplementation when compared to the RES group. The concentrations of arginine, leucine, putrescine and spermidine in type A COT were higher (P < 0.05) in the RES + ARG or RES + NCG group than in the RES group. The mRNA expression levels of inducible nitric oxide synthase (iNOS) and solute carrier family 15, member 1 (SLC15A1) were increased (P < 0.05) while those of progesterone receptor (PGR) and fibroblast growth factor 2 (FGF2) were decreased in type A COT by supplementation with either NCG or RP-Arg compared to the RES group. The results suggest that providing underfed pregnant ewes from d 35 to 110 of gestation with a diet supplemented with NCG or RP-Arg improves placental AA transport, and reduces the expression of angiogenic growth factor genes and steroid anabolism, leading to better fetal development.

Transcriptional control of carbohydrate catabolism by the CcpA protein in the ruminal bacterium Streptococcus bovis.

As a potent, pleiotropic regulatory protein in Gram-positive bacteria, catabolite control protein A (CcpA) mediates the transcriptional control of carbohydrate metabolism in Streptococcus bovis, a lactate-producing bacterium that plays an essential role in rumen acidosis in dairy cows. Although the rumen uptake of carbohydrates is multi-substrate, the focus of S. bovis research thus far has been on the glucose. With the aid of gene deletion, whole-genome sequencing, and transcriptomics, we have unraveled the role of CcpA in carbohydrate metabolism, on the one hand, and acidosis, on the other, and we show that the S. bovis strain S1 encodes "Carbohydrate-Active Enzymes" and that ccpA deletion slows the organism's growth rate and modulates the organic acid fermentation pathways toward lower lactate, higher formate, and acetate in the maltose and cellobiose. Furthermore, this study revealed the different regulatory functions of the CcpA protein in rumen metabolism and acidosis.IMPORTANCEThis study is important as it illustrates the varying regulatory role of the Streptococcus bovis catabolite control protein A protein in carbohydrate metabolism and the onset of acidosis in dairy cattle.

Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model.

BACKGROUND: Exposure to bisphenol A (BPA), an environmental pollutant known for its endocrine-disrupting properties, during gestation has been reported to increase the risk of fetal growth restriction (FGR) in an ovine model of pregnancy. We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta, oxidative stress, inflammatory responses, autophagy and endoplasmic reticulum stress (ERS). However, precise mechanisms underlying the BPA-induced placental dysfunction, and subsequently, FGR, as well as the potential involvement of placental ERS in these complications, remain to be investigated. METHODS: In vivo experiment, 16 twin-pregnant (from d 40 to 130 of gestation) Hu ewes were randomly distributed into two groups (8 ewes each). One group served as a control and received corn oil once a day, whereas the other group received BPA (5 mg/kg/d as a subcutaneous injection). In vitro study, ovine trophoblast cells (OTCs) were exposed to 4 treatments, 6 replicates each. The OTCs were treated with 400 µmol/L BPA, 400 µmol/L BPA + 0.5 µg/mL tunicamycin (Tm; ERS activator), 400 µmol/L BPA + 1 µmol/L 4-phenyl butyric acid (4-PBA; ERS antagonist) and DMEM/F12 complete medium (control), for 24 h. RESULTS: In vivo experiments, pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency, progesterone (P4) level and fetal weight, and an increase in placental estrogen (E2) level, together with barrier dysfunctions, OS, inflammatory responses, autophagy and ERS in type A cotyledons. In vitro experiment, the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy, ERS, pro-apoptosis and inflammatory response, and a decrease in the P4 level and the related protein and gene expressions of antioxidant, anti-apoptosis and barrier function. Moreover, treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine (the increased E2 level and decreased P4 level), OS, inflammatory responses, autophagy, and ERS. However, treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above. CONCLUSIONS: In general, the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs, and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine, OS, inflammatory responses, and autophagy. These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.

New Onset of Tuberculosis Complicating FDG PET/CT Evaluation in Patient With Recent Chimeric Antigen Receptor T-Cell Therapy.

ABSTRACT: A 16-year-old adolescent girl with CD19 chimeric antigen receptor (CAR) T-cell therapy for acute lymphoblastic leukemia experienced new onset of the fever. 18 F-FDG PET/CT studies acquired at 1 and 2 months, respectively, after CAR-T, showed foci of abnormal activity in the mediastinal lymph nodes not seen on the study before therapy. However, these foci of abnormal activity were later proven due to newly developed tuberculosis after CAR T-cell therapy.

Autophagy attenuates placental apoptosis, oxidative stress and fetal growth restriction in pregnant ewes.

Bisphenol A (BPA)-induced oxidative stress (OS) and its potentially associated autophagy and apoptosis have not been studied previously in pregnant ewes. Accordingly, this study investigated the underlying mechanisms of BPA-induced autophagy and apoptosis in the placenta and primary trophoblasts of pregnant ewes exposed to BPA both in vivo and in vitro. In vivo experiment, pregnant Hu ewes (n = 8) were exposed to 5 mg/kg/d of BPA compared to control ewes (n = 8) receiving only corn oil from day 40 through day 110 of gestation. Exposure to BPA during gestation resulted in placental insufficiency, fetal growth restriction (FGR), autophagy, endoplasmic reticulum stress (ERS), mitochondrial dysfunction, OS, and apoptosis in type A placentomes. Regarding in vitro model, primary ovine trophoblasts were exposed to BPA, BPA plus chloroquine (CQ; an autophagy inhibitor) or BPA plus rapamycin (RAP; an autophagy activator) for 12 h. Data illustrated that exposure to BPA enhanced autophagy (ULK1, Beclin-1, LC3, Parkin, and PINK1), ERS (GRP78, CHOP10, ATF4, and ATF6) and apoptosis (Caspase 3, Bcl-2, Bax, P53) but decreased the antioxidant (CAT, Nrf2, HO-1, and NQO1)-related mRNA and protein expressions as well as impaired the mitochondrial function. Moreover, treatment with CQ exacerbated the BPA-mediated OS, mitochondrial dysfunction, apoptosis, and ERS. On the contrary, RAP treatment counteracted the BPA-induced trophoblast dysfunctions mentioned above. Overall, the findings illustrated that BPA exposure could contribute to autophagy in the ovine placenta and trophoblasts and that autophagy, in turn, could alleviate BPA-induced apoptosis, mitochondrial dysfunction, ERS, and OS. These results offer new mechanistic insights into the role of autophagy in mitigating BPA-induced placental dysfunctions and FGR.

Chimeric Antigen Receptor T-Cell Therapy of Neurolymphomatosis Monitored by FDG PET/CT.

ABSTRACT: 18 F-FDG PET/CT was performed to evaluate possible recurrent B-cell lymphoblastic lymphoma in a 34-year-old man. The images showed multiple foci of increased activity in the nerve root and peripheral nerve. A biopsy confirmed the diagnosis of neurolymphomatosis. After receiving chemotherapy, PET/CT showed progressive disease. The patient subsequently received the CD-19 chimeric antigen receptor T-cell therapy. A follow-up PET/CT acquired 30 days after chimeric antigen receptor T-cell therapy revealed no abnormal FDG activity.

Dietary rumen-protected choline supplementation regulates blood biochemical profiles and urinary metabolome and improves growth performance of growing lambs.

This study aimed to assess the growth performance and blood metabolites, as well as metabolic profiles in the urine of lambs fed on dietary rumen-protected choline (RPC). Thirty-six Dorper × Hu lambs weighing approximately 20 kg were equally assigned to three groups, and fed on three diets supplemented with different RPC concentrations (0, 0.25% and 0.75%) for 45 days. Supplementation of RPC significantly increased average daily gain (ADG) and decreased feed-to-gain ratio (F/G) of lambs (p < 0.05). Dietary RPC was significantly associated with elevated plasma high-density lipoprotein (HDL) and suppressed low-density lipoprotein (LDL) levels when compared to the control group (p < 0.05). Moreover, concentrations of very-low-density lipoprotein (VLDL) exhibited an increasing trend (p = 0.065), whereas ß-hydroxybutyrate (BHBA) levels decreased (p = 0.086) in plasma. Analysis of urine metabolome revealed that RPC supplementation significantly suppressed urinary concentrations of pyruvate (p < 0.05), while increased urinary concentrations of trimethylamine oxide, p-cresol, phenylacetylglycine and hippurate (p < 0.05). These findings suggest that RPC supplementation can promote weight gain, alter plasma lipid metabolism and modify urinary metabolome which is correlated with energy metabolism, lipid metabolism and intestinal microbial metabolism in lambs. In conclusion, based on our findings, we recommend 0.25% RPC as a supplement for growing lambs.

Dietary N-carbamylglutamate and L-arginine supplementation improves redox status and suppresses apoptosis in the colon of intrauterine growth-retarded suckling lambs.

Previous studies have revealed that dietary N-carbamylglutamate (NCG) or L-arginine (Arg) improves small intestinal integrity and immune function in suckling Hu lambs that have experienced intrauterine growth retardation (IUGR). Whether these nutrients alter redox status and apoptosis in the colon of IUGR lambs is still unknown. This study, therefore, aimed at investigating whether dietary supplementation of Arg or NCG alters colonic redox status, apoptosis and endoplasmic reticulum (ER) stress and the underlying mechanism of these alterations in IUGR suckling Hu lambs. Forty-eight 7-d old Hu lambs, including 12 with normal birth weight (4.25 ± 0.14 kg) and 36 with IUGR (3.01 ± 0.12 kg), were assigned to 4 treatment groups (n = 12 each; 6 males and 6 females) for 3 weeks. The treatment groups were control (CON), IUGR, IUGR + Arg and IUGR + NCG. Relative to IUGR lambs, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) content, as well as proliferation index, were higher (P < 0.05) whereas reactive oxygen species (ROS), malondialdehyde (MDA) levels and apoptotic cell numbers were lower (P < 0.05) in colonic tissue for both IUGR + Arg and NCG lambs. Both mRNA and protein levels of C/EBP homologous protein 10 (CHOP10), B-cell lymphoma/leukaemia 2 (Bcl-2) -associated X protein (Bax), apoptosis antigen 1 (Fas), activating transcription factor 6 (ATF6), caspase 3, and glucose-regulated protein 78 (GRP78) were lower (P < 0.05) while glutathione peroxidase 1 (GPx1), Bcl-2 and catalase (CAT) levels were higher (P < 0.05) in colonic tissue for IUGR + Arg and IUGR + NCG lambs compared with IUGR lambs. Based on our results, dietary NCG or Arg supplementation can improve colonic redox status and suppress apoptosis via death receptor-dependent, mitochondrial and ER stress pathways in IUGR suckling lambs.

Dietary L-Arginine or N-Carbamylglutamate Alleviates Colonic Barrier Injury, Oxidative Stress, and Inflammation by Modulation of Intestinal Microbiota in Intrauterine Growth-Retarded Suckling Lambs.

Our previous studies have revealed that dietary N-carbamylglutamate (NCG) and L-arginine (Arg) supplementation improves redox status and suppresses apoptosis in the colon of suckling Hu lambs with intrauterine growth retardation (IUGR). However, no studies have reported the function of Arg or NCG in the colonic microbial communities, barrier function, and inflammation in IUGR-suckling lambs. This work aimed to further investigate how dietary Arg or NCG influences the microbiota, barrier function, and inflammation in the colon of IUGR lambs. Forty-eight newborn Hu lambs of 7 d old were assigned to four treatment groups (n = 12 per group; six male, six female) as follows: CON (normal birth weight, 4.25 ± 0.14 kg), IUGR (3.01 ± 0.12 kg), IUGR + Arg (2.99 ± 0.13 kg), and IUGR + NCG (3.03 ± 0.11 kg). A total of 1% Arg or 0.1% NCG was supplemented in a basal diet of milk replacer, respectively. Lambs were fed the milk replacer for 21 d until 28 d after birth. Compared to the non-supplemented IUGR lambs, the transepithelial electrical resistance (TER) was higher, while fluorescein isothiocyanate dextran 4 kDa (FD4) was lower in the colon of the NCG- or Arg-supplemented IUGR lambs (p < 0.05). The IUGR lambs exhibited higher (p < 0.05) colonic interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), and malondialdehyde (MDA) levels than the CON lambs; the detrimental effects of IUGR on colonic proinflammatory cytokine concentrations and redox status were counteracted by dietary Arg or NCG supplementation. Both IUGR + Arg and IUGR + NCG lambs exhibited an elevated protein and mRNA expression of Occludin, Claudin-1, and zonula occludens-1 (ZO-1) compared to the IUGR lambs (p < 0.05). Additionally, the lipopolysaccharide (LPS) concentration was decreased while the levels of acetate, butyrate, and propionate were increased in IUGR + Arg and IUGR + NCG lambs compared to the IUGR lambs (p < 0.05). The relative abundance of Clostridium, Lactobacillus, and Streptococcus was lower in the colonic mucosa of the IUGR lambs than in the CON lambs (p < 0.05) but was restored upon the dietary supplementation of Arg or NCG to the IUGR lambs (p < 0.05). Both Arg and NCG can alleviate colonic barrier injury, oxidative stress (OS), and inflammation by the modulation of colonic microbiota in IUGR-suckling lambs. This work contributes to improving knowledge about the crosstalk among gut microbiota, immunity, OS, and barrier function and emphasizes the potential of Arg or NCG in health enhancement as feed additives in the early life nutrition of ruminants.

Lactate uptake in the rumen and its contributions to subacute rumen acidosis of goats induced by high-grain diets.

Rumen acidosis is the consequence of feeding rapidly fermentable grain diets and it is considered the most common nutritional disorder in intensive feeding ruminants. Due to that mechanism of catabolism and transformation is driven by multi-factors, the role of ruminal lactate and its contribution to subacute rumen acidosis has not been well defined yet. The aim of this study is to evaluate the effects of SARA on the production, absorption, circulation, and transformation of lactate in the rumen. In this study, rumen samples were collected from 12 adult Saanen goats (44.5 ± 4.6 kg BW) equipped with permanent rumen cannula to measure rumen fermentation parameters, organic acids production, microbial profiles, and blood indicators to identify the occurrence of SARA. To further investigate the change in the disappearance rate of ruminal lactate, rumen fluid was collected and a batch culture was performed. The results showed that the clearance rate of ruminal lactate was accelerated by SARA, and the concentration of the ruminal lactate pool was stable. In addition, the rumen liquid dilution rate and the rumen liquid flow rate under the SARA condition of goats were lower than that in normal conditions. The ruminal lactate flow rate had no difference throughout the process of fermentation. However, in vitro data showed that the disappearance of lactate was reduced in SARA. By measuring the conversion of sodium L-[3-13C]-lactate in batch culture, it was found that the percentage of lactate converted to propionate was significantly lower in the SARA treatment and 16.13% more lactate converted to butyrate under SARA condition. However, the percentage of lactate transformed into acetate and butyrate was significantly increased in the SARA treatment than that of control. The relative population of total protozoa count in SARA was significantly reduced, while the relative population of Lactobacillus fermentum, Streptococcus bovis, Butyrivibrio fibrisolvens, Megasphaera elsdenii, and Selenomonas ruminantium in the SARA treatment was significantly induced (p < 0.05). It is concluded that the transformation of lactate into butyrate may promote the development of SARA. These findings provide some references to the diet formulation for preventing SARA.

Thiamine Supplementation Alleviates Lipopolysaccharide-Triggered Adaptive Inflammatory Response and Modulates Energy State via Suppression of NFκB/p38 MAPK/AMPK Signaling in Rumen Epithelial Cells of Goats.

Studies have shown that exogenous thiamine (THI) supplementation can alleviate inflammation and promote rumen epithelial development in goats and cows. This research aimed to evaluate the effect of THI supplementation on LPS-induced inflammation and energy metabolic dysregulation in RECs of goats. Cells were stimulated with either 5 µg/mL THI for 18 h (THI group) or with 5 µg/mL LPS for 6 h (LPS group). The CON group was stimulated with DMEM/F-12 medium without THI for 18 h. The LPTH group was pretreated with THI for 18 h, followed by LPS stimulation for 6 h. THI supplementation decreased the ROS content (p < 0.05), as well as the ratios of phosphorylated (p)-p65 to p65 (p < 0.05) and p-AMPKα to AMPKα (p < 0.05). Interestingly, when the p38 gene was overexpressed in the LPTH group, the ratio of p-p65 to p65 and p-AMPKα to AMPKα proteins significantly increased, and ATP content decreased (p < 0.05). Our results suggest that THI possesses anti-inflammatory and metabolic-modulatory effects in RECs. The mechanism is largely related to the suppression of the NF-κB/p38 MAPK/AMPK signaling pathway. Additionally, we also revealed that THI supplementation can inhibit LPS-induced oxidative damage and apoptosis to protect mitochondrial function in RECs.

Active Dry Yeast and Thiamine in Synergistic Mode Can Mitigate Adverse Effects of In Vitro Ruminal Acidosis Model of Goats.

Ruminal acidosis is a type of metabolic disorder of high-yielding ruminants which is associated with the consumption of a high-grain diet. It not only harms the productive efficiency, health and wellbeing of the animals but also has detrimental effects on the economy of the farmers. Various strategies have been adapted to control ruminal acidosis. However, none of them have produced the desired results. This research was carried out to investigate the potential of active dry yeast (ADY) and thiamine in a synergistic mode to mitigate in vitro-induced ruminal acidosis. The purpose of this study was to determine how active dry yeast alone and in combination with thiamine affected the ruminal pH, lactate, volatile fatty acids, lipopolysaccharides (LPS) and microbial community in in vitro-induced ruminal acidosis. The experiment comprises three treatment groups, (1) SARA/control, (2) ADY and (3) ADYT (ADY + thiamine). In vitro batch fermentation was conducted for 24 h. The results indicated that ruminal induced successfully and both additives improved the final pH (p < 0.01) and decreased the LPS and lactate (p < 0.01) level as compared to the SARA group. However, the ADYT group decreased the level of lactate below 0.5 mmol/L. Concomitant to fermentation indicators, both the treatment groups decreased (p < 0.05) the abundance of lactate-producing bacteria while enhancing (p < 0.01) the abundance of lactate-utilizing bacteria. However, ADYT also increased (p < 0.05) the abundance of protozoa compared to the SARA and ADY group. Therefore, it can be concluded that ADY and thiamine in synergistic mode could be a better strategy in combating the adverse effects of subacute ruminal acidosis.

Effects of the Gut Microbiota and Barrier Function on Melatonin Efficacy in Alleviating Liver Injury.

Environmental cadmium (Cd) exposure has been associated with severe liver injury. In contrast, melatonin (Mel) is a candidate drug therapy for Cd-induced liver injury due to its diverse hepatoprotective activities. However, the precise molecular mechanism by which Mel alleviates the Cd-induced liver injury, as well as the Mel-gut microbiota interaction in liver health, remains unknown. In this study, mice were given oral gavage CdCl2 and Mel for 10 weeks before the collection of liver tissues and colonic contents. The role of the gut microbiota in Mel's efficacy in alleviating the Cd-induced liver injury was evaluated by the gut microbiota depletion technique in the presence of antibiotic treatment and gut microbiota transplantation (GMT). Our results revealed that the oral administration of Mel supplementation mitigated liver inflammation, endoplasmic reticulum (ER) stress and mitophagy, improved the oxidation of fatty acids, and counteracted intestinal microbial dysbiosis in mice suffering from liver injury. It was interesting to find that neither Mel nor Cd administration induced any changes in the liver of antibiotic-treated mice. By adopting the GMT approach where gut microbiota collected from mice in the control (CON), Cd, or Mel + Cd treatment groups was colonized in mice, it was found that gut microbiota was involved in Cd-induced liver injury. Therefore, the gut microbiota is involved in the Mel-mediated mitigation of ER stress, liver inflammation and mitophagy, and the improved oxidation of fatty acids in mice suffering from Cd-induced liver injury.

Extra arginine supplementation during the suckling period alleviates weaning stress through the regulation of dendritic cells and Notch2 signaling in piglets.

This study aims to study the effects of extra arginine (Arg) supplementation during the suckling period on the weaning stress and intestinal barrier function of breastfed piglets. Forty 7-day-old breastfed piglets divided into the control group (CON) and Arg group (Arg) were fed with extra saline or Arg (250 mg per kg per d body weight), respectively. All piglets were weaned when they were 21 days old. Eight piglets from each group were sacrificed before weaning and on the 3rd-day after weaning, respectively. The results showed that Arg improved the average daily weight gain of piglets before weaning (P < 0.01) and decreased the average daily weight loss after weaning (P < 0.05). Weaning decreased the ratio of the villus length versus crypt depth (V/C) in the SI (P < 0.001), while Arg increased the V/C of the jejunum (P < 0.05). Arg increased the levels of immunoglobulins in the serum and SI (P < 0.05), decreased pro-inflammatory cytokines and increased anti-inflammatory cytokines in the SI (P < 0.05). In addition, Arg supplementation increased the numbers of SWC3a+CD40+ (P < 0.01) and SWC3a+SLAII+ DCs (P < 0.05), down-regulated Notch2 expression and up-regulated Jagged1 expression in the ilea of weaning piglets (P < 0.05). In conclusion, Arg supplementation during the suckling period decreased the LDH leakage in the SI, improved the intestinal morphology, down-regulated the contents of pro-inflammatory cytokines, accelerated the accumulation of DC precursors before weaning and increased the number of mature DCs after weaning, and thus improved the growth performance and reduced the weaning stress of piglets, and this might be associated with the regulation of Notch2 signaling.

Subacute ruminal acidosis in dairy herds: Microbiological and nutritional causes, consequences, and prevention strategies.

Dairy cattle are frequently fed high-concentrate (HC) diets in modern intensive feeding systems, especially in the transition period. During this period, cows face many alterations that include hormonal changes and shifting to a lactating state. Switching to a HC diet that may disrupt the ruminal microbiota balance can lead to subacute ruminal acidosis (SARA). Moreover, the main factor shaping the rumen microbiota is dietary composition, especially the ratio of starch to fibrous carbohydrates. Feeding highly fermentable carbohydrate diets after adaptation to forage diets leads to a rumen fermentation rate that exceeds rumen absorption and buffering rates, resulting in a reduction in ruminal pH. As a result of Gram-negative bacterial cell lysis, an increase in harmful ruminal bacterial metabolites, including lipopolysaccharide, lactic acid, and histamine, is observed. The interactions between the host immune system and the ruminal microbiota play an essential role in many physiological processes and the development of the disorder. Progress in DNA sequencing and bioinformatics platforms provides new opportunities to investigate the composition of ruminal microbes and yields unique advances in understanding ecology of the rumen. Subacute ruminal acidosis is linked with a change in the ruminal microbiota structure and richness and with other metabolic disorders; such as rumenitis, milk fat depression, laminitis, and liver abscesses. Therefore, this review aims to explore a better understanding of the crosstalk between diet and microbiota in the prevalence of rumen acidosis and its consequences, which is crucial for control strategies such as feeding management, and supplementation with thiamine, prebiotics, and probiotics.

Dietary Palygorskite Clay-Adsorbed Nano-ZnO Supplementation Improves the Intestinal Barrier Function of Weanling Pigs.

This study aimed to investigate the effects of PNZ on intestinal mucosal barrier function in weaning piglets. A total of 210, 21-day-old piglets with similar body weights (6.30 ± 0.51 kg) were randomly allocated into seven groups: control group (CON), antibiotic group (ANT), ZnO group (ZO), nano-ZnO group (NZO) and low, middle, and high PNZ groups (LPNZ, MPNZ, and HPNZ). The seven groups were, respectively, fed control diets or control diets supplemented with antibiotics; 3,000 mg/kg ZnO; 800 mg/kg nano-ZnO; 700, 1,000, or 1,300 mg/kg PNZ. More integrated intestinal villi were observed in the LPNZ group. In the jejunum of LPNZ group, the crypt depth significantly decreased (P < 0.05), and the ratio of villus height to crypt depth (V/C) significantly increased (P < 0.05). In addition, the villus width and surface area of the ileum were significantly increased in the LPNZ group (P < 0.05). Dietary supplementation with PNZ can significantly increase the number of goblet cells in the mucosa of the jejunum and ileum (P < 0.05), decrease the contents of TNF-α and IL-1ß (P < 0.05), and increase the contents of sIgA and IL-4 in the jejunal and ileal mucosa (P < 0.05). Meanwhile, the mRNA expression of MCU2 and ZO1 in PNZ group were significantly increased (P < 0.05), the mRNA expression of TLR4 and MyD88 was downregulated (P < 0.05). With increasing levels of PNZ, decreased proinflammatory cytokines and increased intestinal mucosal barrier function in weaned pigs was observed. In conclusion, supplementation with PNZ could effectively improve the intestinal barrier function of weanling piglets and potentially could replace the use of high doses of ZnO and antibiotics. The appropriate dose of PNZ for supplementation was 700 mg/kg.