Yogurt Enriched with Inulin Ameliorated Reproductive Functions and Regulated Gut Microbiota in Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome Mice.

The effects of synbiotic yogurt supplemented with inulin on the pathological manifestations and gut microbiota-bile acid axis were investigated using a dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) mice model. Female C57BL/6J mice were injected subcutaneously with DHEA at a dose of 6 mg/100 g BW for 20 days to establish a PCOS mouse model. Then, the PCOS mice were treated with yogurt containing inulin (6% w/w) at 15 mL/kg BW for 24 days. Results showed that supplementation of synbiotic yogurt enriched with inulin to PCOS mice decreased the body weight gain, improved estrus cycles and ovary morphology, and reduced the levels of luteinizing hormone while increasing the levels of follicle-stimulating hormone and interleukin-22 in serum. At the genus level, synbiotic yogurt increased the relative abundance of Lactobacillus, Bifidobacterium, and Akkermansia. PICRUSt analysis indicated that KEGG pathways including bile acid biosynthesis were changed after inulin-enriched synbiotic yogurt supplementation. Synbiotic yogurt enriched with inulin also modulated the bile acid profiles. In conclusion, inulin-enriched synbiotic yogurt alleviated reproductive dysfunction and modulated gut microbiota and bile acid profiles in PCOS mice.

Betaine hydrochloride addition in Bama mini-pig's diets during gestation and lactation enhances immunity and alters intestine microbiota of suckling piglets.

BACKGROUND: Maternal nutrition during gestation and lactation is essential for offspring's health. The present study aimed to investigate the effects of betaine hydrochloride addition to sow diets during gestation and lactation on suckling piglet's immunity and intestine microbiota composition. Forty Bama mini-pigs were randomly allocated into two groups and fed a basal diet (control group) and a basal diet supplemented with 3.50 kg ton-1 betaine hydrochloride (betaine group) from day 3 after mating to day 21 of lactation. After 21 days of the delivery, 12 suckling piglets from each group with similar body weight were selected for sample collection. RESULTS: The results showed that maternal betaine hydrochloride addition decreased (P < 0.05) the plasma levels of interleukin (IL)-1ß, IL-2, IL-6, and tumor necrosis factor-α in suckling piglets. Furthermore, dietary betaine hydrochloride addition in sow diets increased (P < 0.05) the villus height (VH) and VH to crypt depth ratio in the jejunum and ileum of suckling piglets. In the piglets' intestinal microbiota community, the relative abundances of Roseburia (P < 0.05) and Clostridium (P = 0.059) were lower in the betaine group compared to those in the control group. Moreover, betaine hydrochloride addition in sow diets decreased the colonic tyramine (P = 0.091) and skatole (P = 0.070) concentrations in suckling piglets. CONCLUSION: Betaine hydrochloride addition in sow diets enhanced the intestinal morphology, improved immunity, and altered intestinal microbiota of suckling piglets. These findings indicated that betaine hydrochloride addition in sow diets during gestation and lactation will impact suckling piglets' health. © 2021 Society of Chemical Industry.

Calcium-Enriched Pumpkin Affects Serum Leptin Levels and Fat Content in a Rat Model of Postmenopausal Osteoporosis.

Because the world's population is deficient in dietary calcium, it is important to search for new sources of this essential mineral for the bones and the entire body. One of the innovative foods that could act as such a source is pumpkin enriched with calcium lactate by means of osmotic dehydration. Providing the body with easily absorbable calcium may have beneficial effects on the reconstruction of bone tissue. Postmenopausal osteoporosis is associated with body weight and fat mass gain, and the aim of the present study was to evaluate the effect of consuming enriched pumpkin on the levels of adipokines and cytokines produced by the adipose tissue. This study was conducted on 12-month-old female Wistar rats that received nutritional intervention for 12 weeks. After termination of the rats, the levels of leptin, adiponectin, interleukin 31 and interleukin 33 in serum and adipose tissue were determined, and the femurs were examined histopathologically. It was demonstrated that calcium-enriched pumpkin reduced bone marrow femoral adipocytes and also markedly decreased serum leptin levels in groups of rats after ovariectomy, which was associated with a decrease of fat content. Additionally, it seems that calcium-enriched pumpkin may reduce body weight gain often observed after menopause.

Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS.

The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (rs = -0.495), PCT (rs = -0.413), IL-6 (rs = -0.429), IL-1ß (rs = -0.440) and IL-10 (rs = -0.461). Positive associations were found for CD8+ T cells (rs = 0.636), NK cells (rs = 0.772), total IgG (rs = 0.493) and PaO2/FiO2 ratios (rs = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.

Standardized astragalus extract for attenuation of the immunosuppression induced by strenuous physical exercise: randomized controlled trial.

BACKGROUND: This paper aimed to verify how a supplementation of rower's diet with Astragalus Membranaceus Root (AMR) modulated their immune system response to maximal physical exertion. METHODS: The double-blind study included 18 members of the Polish Rowing Team assigned to the supplemented group (n = 10), and the placebo group (n = 8). The participants performed a 2000 m test on a rowing ergometer at the beginning and at the end of the six-week of intensive training camp during which the supplemented group received 500 mg of AMR. Blood samples were obtained prior to, 1 min after completing, and 24 h after the exertion test. The levels of interleukin 2 (IL2), interleukin 4 (IL4), interleukin 10 (IL10), interferon ɤ (IFN-É£), and lactic acid were determined. Subpopulations of T regulatory lymphocytes [CD4+/CD25+/CD127-] (Treg), cytotoxic lymphocytes [CD8+/TCRαß+] (CTL), natural killer cells [CD3-/CD16+/CD56+] (NK), and TCRδγ-positive cells (Tδγ) were determined with flow cytometry. RESULTS: After the camp, the initial NK and Treg levels sustained at the baseline, while Tδγ counts increased relative to the levels in the placebo group. In the supplemented subgroup, a decrease in IL2 level in reaction to maximal exertion clearly deepened while the change in IL-2/IL-10 level induced by the recovery after this exertion clearly increased, relative to the changes in the placebo group. CONCLUSIONS: AMR restored the immunological balance in strenuously trained athlets through a stabilization of NK and Treg cells with a positive trend in Tδγ towards Th1 response during restitution by cytokine IL2 modulation.

Efficacy and mechanism of traditional chinese medicine gel in sports-related soft tissue injury / Eficácia e mecanismo do tradicional gel da medicina chinesa em lesões desportivas de tecidos moles / Eficacia y mecanismo del gel de medicina tradicional china en lesiones deportivas de tejidos blandos

ABSTRACT Soft tissue injury is the most common disease in orthopedics, and it is also the most easily neglected disease in sports. Without timely and effective treatment, it is easy to develop into malignant strain and seriously affect life and sports. In view of this, the aim of this study is to analyze the effect and mechanism of traditional Chinese medicine gel in treating such injuries in the light of the characteristics of sports-related soft tissue injury. The right gastrocnemius muscle injury was simulated in 36 adult male rats. Chinese medicine gel and tincture were used to treat it. The contents of interleukin, alanine aminotransferase, blood urea nitrogen and prostaglandin E2 in the blood of rats under different courses of treatment were analyzed to explore recovery in four rats. The results showed that the levels of interleukin and prostaglandin E2 in the blood of rats treated with drugs were significantly lower than those in the control group (p<0.05), indicating that both drugs have obvious therapeutic effects on soft tissue injury. The content of interleukin in the blood of the Chinese medicine gel group was slightly lower than that of the tincture group, indicating that the Chinese medicine gel could affect the recovery of soft tissue injury by affecting leukocyte interleukin. This result is helpful in the treatment of soft tissue injury in sports and to further improve the therapeutic effect of traditional Chinese medicine gel.

RESUMO A lesão dos tecidos moles é a doença mais comum na ortopedia, e é também a doença mais facilmente negligenciada nos esportes. Sem tratamento ágil e eficaz, facilmente evolui para luxações malignas, afetando seriamente a vida e a prática de esportes. Em vista disso, o objetivo deste estudo é analisar o efeito e o mecanismo do gel da medicina tradicional chinesa no tratamento de tais lesões, com base nas características da lesão dos tecidos moles relacionada à prática esportiva. Estimulou-se lesão do músculo gastrocnêmio direito em 36 ratos adultos. O gel e a tintura chinesa foram usados para o tratamento. Foram analisados os conteúdos de interleucina, alanina aminotransferase, ureia sanguínea azoto e prostaglandina E2 no sangue dos ratos sob diferentes tratamentos, de modo a explorar a recuperação de quatro ratos. Os resultados mostraram que os níveis de interleucina e prostaglandina E2 no sangue dos ratos tratados com medicamentos eram significativamente inferiores aos do grupo controle (p<0.05), indicando que ambos os fármacos têm efeitos terapêuticos óbvios sobre lesões dos tecidos moles. O teor de interleucina no sangue do grupo gel chinês medicinal mostrou-se ligeiramente inferior ao do grupo tintura, indicando que o gel medicinal chinês pode afetar a recuperação da lesão nos tecidos moles, afetando o leucócito interleucina. Este resultado é útil para o tratamento de lesões dos tecidos moles relacionadas à prática esportiva e para melhorar ainda mais o efeito terapêutico do gel da medicina chinesa tradicional.

RESUMEN La lesión de los tejidos blandos es la enfermedad más común en la ortopedia, y es también la enfermedad más fácilmente descuidada en los deportes. Sin tratamiento ágil y eficaz, fácilmente evolucionan a luxaciones malignas, afectando seriamente la vida y la práctica de deportes. En vista de eso, el objetivo de este estudio es analizar el efecto y el mecanismo del gel de la medicina tradicional china en el tratamiento de tales lesiones, con base en las características de la lesión de los tejidos blandos relacionada a la práctica deportiva. Se estimuló lesión del músculo gastrocnemio derecho en 36 ratones adultos. El gel y la tintura china fueron usados para el tratamiento. Fueron analizados los contenidos de interleucina, alanina aminotransferasa, urea sanguínea, nitrógeno y prostaglandina E2 en la sangre de los ratones bajo diferentes tratamientos, de modo de explorar la recuperación de cuatro ratones. Los resultados mostraron que los niveles de interleucina y prostaglandina E2 en la sangre de los ratones tratados con medicamentos eran significativamente inferiores a los del grupo control (p<0.05), indicando que ambos fármacos tienen efectos terapéuticos obvios sobre lesiones de los tejidos blandos. El tenor de interleucina en la sangre del grupo gel chino medicinal se mostró ligeramente inferior al del grupo tintura, indicando que el gel medicinal chino puede afectar la recuperación de la lesión en los tejidos blandos, afectando el leucocito interleucina. Este resultado es útil para el tratamiento de lesiones de los tejidos blandos relacionadas a la práctica deportiva y para mejorar aún más el efecto terapéutico del gel de la medicina china tradicional.

Supplementation of Moringa oleifera leaf powder orally improved productive performance by enhancing the intestinal health in rabbits under chronic heat stress.

Heat stress jeopardizes animal's growth and health mainly through induction of oxidative stress and inflammation. The current study investigated the effects of Moringa oleifera leaf powder (MOLP) supplementation on productive performance and intestinal health of rabbits under chronic heat stress (HS). Young New Zealand White rabbits (male) at the age of 32 weeks (n = 21, mean body weight of 3318 ± 171 g) for four weeks' period were reared on commercial pelleted diet and divided into three groups: control (CON, 25 °C), HS (35 ± 1 °C) and HS (35 ± 1 °C) with MOLP (HSM) supplemented orally (200 mg/kg body weight). The results demonstrated that rabbits in the HSM group had reduced rectal temperature, respiration rate and improved FCR due to improved daily gain and better crude fiber (NDF) digestibility (P < 0.05) compared with HS group. MOLP improved intestinal integrity and function as indicated by lower serum diamine oxidase level and increased jejunal weight, length, villus height and ratio of villus height to crypt depth than heat-stressed rabbits. MOLP reversed the increased levels of serum cortisol, metabolic indicators i.e. glucose, insulin, and reduced concentrations of serum triiodothyronine. MOLP supplementation also significantly down-regulated the mRNA expression of tumor necrosis factor alpha (α), heat shock protein A2, glutathione peroxidase-1, interleukin (IL)-1α and increased the expression of IL-6. In conclusion, MOLP supplementation could enhance intestinal health along with production and metabolic indicators by alleviating the oxidative stress and inflammatory response in small intestine of hyper-thermic rabbits.

Antifibrotic effect of curcumin, N-acetyl cysteine and propolis extract against bisphenol A-induced hepatotoxicity in rats: Prophylaxis versus co-treatment.

AIMS: Bisphenol A (BPA) has been shown to induce liver fibrosis in rodents. Therefore, this study examined the protective effect of a triple combination of curcumin (Cur), N-acetyl cysteine (NAC) and propolis (Prp) extract against BPA-induced hepatic fibrosis. METHODS: 100 Wistar male rats were equally assigned into 10 groups; one group was designated as control. 10 rats were gavaged with BPA (50 mg/kg/day) for 8 wk and left un-treated (BPA group). The remaining 80 rats were divided into 8 groups, distributed in 2 models. Protective model: rats were daily co-treated with BPA and Cur (100 mg/kg, p.o) or NAC (150 mg/kg, p.o) or Prp (200 mg/kg, p.o) or their combination for 8 wk. Preventive model: rats were daily treated with Cur or NAC or Prp or their combination for 4 wk before BPA administration and then in the same manner as protective model. KEY FINDINGS: Current treatment interventions significantly alleviated BPA-induced hepatic damage and fibrosis. They also restored pro-oxidant/antioxidant balance, shifted cytokine balance towards the anti-inflammatory side, decreasing interleukin-1ß/interleukin-10 ratio. Moreover, these compounds seem to exert anti-apoptotic effects by increasing the immunoexpression of B-cell lymphoma 2 in hepatocytes and decreasing hepatic caspase-3 content. Finally, they ameliorated extracellular matrix turn over through down-regulation of matrix metalloproteinase-9 and up-regulation of tissue inhibitor of matrix metalloproteinase-2 genetic expression. SIGNIFICANCE: Current treatments guarded against BPA-induced hepatic fibrosis due to their antioxidant, anti-inflammatory and anti-apoptotic properties, decreasing extracellular matrix turnover. Interestingly, the triple therapy provided hepatoprotection superior to monotherapy. Besides, prophylactic and concurrent treatments seem to be more effective than concurrent treatments.

The role of serum inflammatory cytokines and berberine in the insulin signaling pathway among women with polycystic ovary syndrome.

OBJECTIVE: To study the role of selected serum inflammatory cytokines and berberine in the insulin signaling pathway among women with polycystic ovary syndrome (PCOS). METHODS: Selected serum inflammatory cytokines were analyzed in the particle cells, which were interfered by berberine, from 78 infertile women who were to be treated with In Vitro Fertilization (IVF) /Intracytoplasmic Sperm Injection-Embryo Transfer (icsi-et). Among them, 49 patients had PCOS infertility, and 29 were non-PCOS patients whose infertility resulted from fallopian tube and male factors. The elisa method was used to detect the changes in the expression levels of inflammatory factors in the cells. The correlations between the serum inflammatory cytokine expression levels and the corresponding clinical hormones were analyzed. The changes in the expression (mRNA and protein) levels of the serum inflammatory cytokines were studied by real-time quantitative PCR and protein printing. Fluorescence microscope and flow cytometry were used to detect the glucose uptake capacity of ovarian granulosa cells in PCOS patients under the action of insulin after berberine. RESULTS: In the PCOS group, IL-17a (P = 0.001), IL-1Ra (P<0.0001), and IL-6 (P = 0.035) were significantly higher than those in the non-PCOS group. In the non-PCOS group, AMH level was negatively correlated with inflammatory cytokines IL-17a (r = -0.819;P = 0.004), IL-1a (r = -0.716;P = 0.0.02), IL-1b (r = -0.678;P = 0.031), IL-2 (r = -0.765;P = 0.01), and IL-8 (r = -0.705;P = 0.023). However, in the PCOS group, AMH levels were not significantly correlated with the levels of the examined inflammatory cytokines. Berberine significantly reduced the expression level of mTOR mRNA (P = 0.001), and increased the expression level of IRS-1 mRNA (P = 0.009) in the PCOS granule cells. CONCLUSION: In this study, we find that the elevated levels of serum inflammatory factors IL-17a, IL-1Ra, and IL-6 cause women to be in a subclinical inflammatory state for a long time. Abnormal changes in inflammatory factors alter their original negative correlations with AMH levels, thereby weakening the metabolism of glycolipids, promoting insulin resistance, destroying the normal ovulation and fertilization system of women, leading to polycystic ovary syndrome characterized by menstrual thinning and abnormal ovulation. Berberine can improve the sensitivity of insulin by regulating the signal pathway of insulin receptor substrate-1 (IRS-1) and mammalian target of rapamycin (mTOR) in PCOS patients and achieve a therapeutic effect of treating PCOS.

The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives.

BACKGROUND & AIMS: In our previous study, a Seesaw model was proposed for the fluctuation of crucial anti- (IL-10) and pro-inflammatory (Il-6 & IL-17A) cytokines through vitamin D3. In this paper, however, it is intended to extend the mentioned model by assessing the expression mRNA levels of IL-27 and TGF-ß1 as well as the changes of plasma levels of IL-27, TGF-ß1, IL-17A, IL-10, and IL-6 after treatment by vitamin D3. METHOD: Venous blood samples were drawn from Healthy Participants (HP, n = 25) and First-Degree Relative Participants (FDRP, n = 25) as control groups and Multiple Sclerosis Participants (MSP, n = 25) before and after eight weeks of supplementation with 50000 IU vitamin D3. The mRNA expression and plasma concentrations were gauged by using Real-Time PCR and ELISA assay, respectively. RESULTS: The mRNA surfaces of IL-27, as well as TGF-ß1, were up-regulated. However, the plasma levels of TGF-ß1, IL-17A, and IL-6 were significantly different among the three groups. In addition, the plasma levels of IL-27, TGF-ß1, IL-10, IL-17A, and IL-6 significantly changed following the administration of vitamin D3. CONCLUSION: The findings of this paper illustrate that anti-inflammatory cytokines could have a key role in immunomodulatory functions due to their anti-inflammatory functions. To conclude, this might contribute to preventing the pathophysiological process of MS. Also, the proposed model could be used as a preventive way on disposed people to multiple sclerosis, particularly in first degree relatives of these patients.

Comparing efficacy and safety of regorafenib versus pemetrexed in lung cancer: A preliminary clinical trial evaluating effect of inflammatory biomarkers on disease progression.

This pilot clinical trial was designed to compare the efficacy and safety of regorafenib versus pemetrexed in Chinese patients with early stage of lung cancer. Also, the effect of inflammatory biomarkers on disease progression among Lung cancer patients who received regorafenib versus pemetrexed was evaluated in the present study. The patients who were diagnosed with early stage of lung cancer were enrolled. The eligible participants were randomized to receive regorafenib 160 mg (orally once daily for the first 21 days of each 28-day cycle) plus BSC or pemetrexed 500 mg/m2 intravenously (Day 1 of each 21-day cycle in combination with cisplatin 75 mg/m2 i.v. beginning 30 minutes after pemetrexed administration) plus BSC in a 1:1 ratio. Efficacy measures such as overall survival, progression-free survival and overall response were assessed after regorafenib and pemetrexed treatment. Safety of after regorafenib and pemetrexed treatment was also assessed. Blood was collected into a test tube pre-washed with chilled EDTA tubes, and then centrifuged to collect plasma sample for estimation of inflammatory biomarkers of interest. Survival time in respect to disease progression was also assessed. Also, biomarker assessments were made at each visit, to see whether inflammatory biomarker has any specific role on survival or in predicting progression of lung cancer. The present study results show that the safety and efficacy profile of regorafenib and pemetrexed was found similar in Chinese patients with early stage lung cancer. In general, regorafenib and pemetrexed treatment was well tolerated in Chinese patients with early stage Lung cancer. The results of this pilot study showed that inflammatory biomarkers such as interleukin 6 and interleukin 17A play an important role predicting progression of early stage lung cancer among Chinese patients.

Polysaccharide from the Seeds of Plantago asiatica L. Protect Against Lipopolysaccharide-Induced Liver Injury.

Previous studies have proven that polysaccharide obtained from the seeds of Plantago asiatica L. (PLCP) could induce maturation of murine dendritic cells, promote defecation, and possess antioxidant activity in vitro. However, the effect of PLCP on lipopolysaccharide (LPS)-induced liver injury in mice has been rarely reported. In this study, we investigated the anti-inflammatory effect of PLCP on LPS-induced liver injury. Mice were pretreated orally with different dose of PLCP for 3 weeks. On day 22, they were injected intraperitoneally with LPS and sacrificed 12 h later. The results showed that PLCP inhibited the excessive production of tumor necrosis factor-α, interleukin (IL)-6, IL-10, IL-2, and IL-1ß in mouse serum and liver. PLCP also improved glutathione peroxidase and total antioxidant capacity activities in mouse liver. In addition, PLCP inhibited nitric oxide, inducible nitric oxide synthase, and cyclooxygenase-2 expression, and increased metallothionein production in mouse liver. Consequently, PLCP may possess protective effects on inflammatory associated liver injury.

Effect of Resveratrol-Enriched Rice on Skin Inflammation and Pruritus in the NC/Nga Mouse Model of Atopic Dermatitis.

Resveratrol-enriched rice (RR) was developed using genetic engineering to combine the properties of resveratrol and rice. To evaluate the effect of RR on pruritic skin inflammation in atopic dermatitis (AD)-like skin lesions, we used dinitrochlorobenzene (DNCB)-induced NC/Nga mice and an in vitro 3D skin model. Normal rice (NR), resveratrol, and RR were topically applied to mice dorsal skin, following which the dermatitis index and scratching frequency were calculated. Histological examination was performed by hematoxylin and eosin and immunohistochemistry staining of IL-31 level. The level of immunoglobulin E (IgE) and IL-31 in the serum was determined by enzyme-linked immunosorbent assay (ELISA). The cytotoxicity of RR and the expression levels of pro-inflammatory cytokines were also determined in cultured human keratinocytes and a 3D skin model. RR significantly reduced scratching frequency, decreased the dermatitis severity and trans-epidermal water loss (TEWL) and improved skin hydration in DNCB-induced NC/Nga mice. RR also significantly decreased serum IL-31 and IgE levels and suppressed the production of IL-6 in human keratinocytes and the 3D skin model. Our study indicates that the synergistic effect of rice and resveratrol manifested by the topical application of RR can serve as a potential alternative therapy for chronic skin inflammatory diseases such as AD.

Curcumin and Resveratrol Regulate Intestinal Bacteria and Alleviate Intestinal Inflammation in Weaned Piglets.

Human infants or piglets are vulnerable to intestinal microbe-caused disorders and inflammation due to their rapidly changing gut microbiota and immaturity of their immune systems at weaning. Resveratrol and curcumin have significant anti-inflammatory, bacteria-regulating and immune-promoting effects. The purpose of this study was to investigate whether dietary supplementation with resveratrol and curcumin can change the intestinal microbiota and alleviate intestinal inflammation induced by weaning in piglets. One hundred eighty piglets weaned at 21 ± 2 d were fed a control diet (CON group) or supplemented diet (300 mg/kg of antibiotics, ANT group; 300 mg/kg of resveratrol and curcumin, respectively, HRC group; 100 mg/kg of resveratrol and curcumin, respectively, LRC group; 300 mg/kg of resveratrol, RES group; 300 mg/kg of curcumin, CUR group) for 28 days. The results showed that compared with the CON group, curcumin alone and antibiotics decreased the copy numbers of Escherichia coli. Both curcumin and resveratrol down-regulated the level of Toll-like-receptor 4 mRNA and protein expression in the intestine to inhibit the release of critical inflammation molecules (interleukin-1ß, tumor necrosis factor-α), and increase the secretion of immunoglobulin. Our results suggested that curcumin and resveratrol can regulate weaned piglet gut microbiota, down-regulate the TLR4 signaling pathway, alleviate intestinal inflammation, and ultimately increase intestinal immune function.

Effect of Preperitoneal Versus Epidural Analgesia on Postoperative Inflammatory Response and Pain Following Radical Cystectomy: A Prospective, Randomized Trial.

OBJECTIVES: Continuous wound infiltration of local anesthetics has been proposed as an alternative to epidural analgesia during abdominal surgery. Cytokines have a major role in inflammatory changes caused by surgery. This study aimed to compare the effects of continuous preperitoneal versus epidural analgesia on inflammatory cytokines postoperatively. MATERIALS AND METHODS: Forty patients scheduled for radical cystectomy were included in this observer-blinded, randomized trial; patients were randomly assigned into 2 groups to receive; continuous preperitoneal wound infiltration (PPB) or epidural analgesia (EDB). Serum levels of interleukins (IL1ß, IL6, IL10, and tumor necrosis factor α) were measured at baseline (before induction of anesthesia), preinfusion (before the start of local anesthetic infusion), 6 and 24 hours postoperatively. Visual Analog Scale at rest/movement (VAS-R/M), time to the first request of analgesia, total morphine consumption, sedation score, hemodynamics, and side effects were observed 24 hours postoperatively. RESULTS: There was a significant reduction in IL6, IL1ß and increase in IL10 in PPB compared with EDB at 6 and 24 hours postoperatively and compared with preinfusion levels (P≤0.001). In EDB, a significant increase in IL1ß, IL10, and tumor necrosis factor α at 6 hours compared with preinfusion levels (P≤0.002). VAS-R/M was significantly decreased at 2, 4, 6, 8, and 12 hours in EDB compared with PPB (P≤0.014), with no significant difference in the mean time to the first request of analgesia and total morphine consumption between the 2 groups. CONCLUSION: Continuous preperitoneal analgesia better attenuated postoperative inflammatory response and provided a comparable overall analgesia to that with continuous epidural analgesia following radical cystectomy.

Effects of Desloratadine Citrate Disodium on Serum Immune Function Indices, Inflammatory Factors and Chemokines in Patients with Chronic Urticaria.

OBJECTIVE: To determine the effects of desloratadine citrate disodium on serum immunological function indices (IgE, C3 and C4), inflammatory factors (IL-4, IL-17 and IL-33), and chemokines (MCP-1, RANTES and Eotaxin) in patients with chronic urticaria. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Department of Dermatology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, China, from January 2017 to January 2018. METHODOLOGY: A total of 128 patients with chronic urticaria were randomly divided into a control group and an observation group, with 64 patients in each group. The patients in the control group were treated with loratadine and those in the observation group were treated with desloratadine citrate disodium. After 4 weeks of treatment, the serum levels of immune function indices (IgE, C3 and C4), inflammatory factors (IL-4, IL-17 and IL-33), and chemokines (MCP-1, RANTES and Eotaxin) were determined. RESULTS: After 4 weeks of treatment, the levels of serum IgE, IL-4, IL-17, IL-33, MCP-1, RANTES and Eotaxin in the observation group were lower than those in the control group (all p<0.001). The levels of serum C3 and C4 in the observation group were higher than those in the control group (both p<0.001). CONCLUSION: Desloratadine citrate disodium can effectively reduce the severity of chronic urticaria, and its therapeutic mechanism may be related to balancing Th1/Th2 cell function, regulating inflammatory mediators and inhibiting the action of chemokines.

Kadsura heteroclita stem suppresses the onset and progression of adjuvant-induced arthritis in rats.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune diseased state, characterized by hyperplasia of the synovial membrane, degradation of cartilage, and bone erosion of diarthrodial joints. Kadsura heteroclita (Roxb) Craib (Schizandraceae), a traditional Tujia ethnomedicine called Xue Tong in China, has been long used for the prevention and treatment of rheumatic and arthritic diseases, especially in the southern China. This study aimed to evaluate anti-arthritic effects of the ethanol extract of Kadsura heteroclita stems (KHS) on complete Freund's adjuvant (CFA)-induced arthritis (AIA) in rats, as well as to explore the underlying mechanisms of anti-arthritis. METHODS: AIA was established in male Sprague-Dawley (SD) rats as described previously, and animals were daily treated by gavage with KHS ethanol extract (200, 400, or 800 mg/kg) or vehicle (0.3% CMCNa) throughout the 30-day experiment. The incidence and severity of arthritis were evaluated using clinical parameters. At the end of experiments, tissue swelling and bone destruction of the hind paws were assessed by computed tomography (CT) and histopathological analyses. Serum levels of tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), IL-6, and IL-17A and IL-17F were measured by ELISA, and protein expression of matrix metalloproteinases-1 (MMP-1), MMP-3 and tissue inhibitor of MMP-1 (TIMP-1) were detected by Western blot. RESULTS: Treatment with KHS dose-dependently inhibited paw swelling and reduced arthritis scores of AIA rats. CT images displayed that KHS remarkably protected AIA rats from tissue swelling and bone erosion of joints. Histopathological analyses revealed that KHS markedly reduced inflammatory cell infiltration, synovial proliferation, and the formation of pannus in the ankle joints of AIA rats. KHS was found to significantly suppress the production of TNF-α, IL-1 ß, IL-6, IL-17A and IL-17F, inhibited the protein expression of MMP-1 and MMP-3, and elevated the protein expressions of TIMP-1. CONCLUSION: KHS demonstrates potential anti-arthritic effects via inhibiting pivotal mediators of inflammation and cartilage destruction. This study strongly supports identification and isolation of active fractions of KHS which would be a potential candidate for further investigation as a new anti-arthritic botanical drug.

Effects of BMP-2 dose and delivery of microvascular fragments on healing of bone defects with concomitant volumetric muscle loss.

Traumatic composite bone-muscle injuries, such as open fractures, often require multiple surgical interventions and still typically result in long-term disability. Clinically, a critical indicator of composite injury severity is vascular integrity; vascular damage alone is sufficient to assign an open fracture to the most severe category. Challenging bone injuries are often treated with bone morphogenetic protein 2 (BMP-2), an osteoinductive growth factor, delivered on collagen sponge. Previous studies in a composite defect model found that a minimally bridging dose in the segmental defect model was unable to overcome concomitant muscle damage, but the effect of BMP dose on composite injuries has not yet been studied. Here, we test the hypotheses that BMP-2-mediated functional regeneration of composite extremity injuries is dose dependent and can be further enhanced via co-delivery of adipose-derived microvascular fragments (MVF), which have been previously shown to increase tissue vascular volume. Although MVF did not improve healing outcomes, we observed a significant BMP-2 dose-dependent increase in regenerated bone volume and biomechanical properties. This is the first known report of an increased BMP-2 dose improving bone healing with concomitant muscle damage. While high dose BMP-2 delivery can induce heterotopic ossification (HO) and increased inflammation, the maximum 10 µg dose used in this study did not result in HO and was associated with a lower circulating inflammatory cytokine profile than the low dose (2.5 µg) group. These data support the potential benefits of an increased, though still moderate, BMP-2 dose for treatment of bone defects with concomitant muscle damage. Published 2019. This article is a U.S. Government work and is in the public domain in the USA. J Orthop Res.

Protocol for the "Chemobrain in Motion - study" (CIM - study): a randomized placebo-controlled trial of the impact of a high-intensity interval endurance training on cancer related cognitive impairments in women with breast cancer receiving first-line chemotherapy.

BACKGROUND: Up to 80% of breast cancer patients suffer from Cancer Related Cognitive Impairments (CRCI). Exercise is suggested as a potential supportive care option to reduce cognitive decline in cancer patients. This study will investigate the effects of a high-intensity interval endurance training (HIIT) on CRCI in breast cancer patients. Potentially underlying immunological and neurobiological mechanisms, as well as effects on patients' self-perceived cognitive functioning and common cancer related side-effects, will be explored. METHODS: A single-blinded randomized controlled trial will be carried out. The impact of HIIT on CRCI will be compared to that of a placebo-intervention (supervised myofascial release training). Both interventions will be conducted simultaneously with the patients' first-line chemotherapy treatment typically lasting 12-18 weeks. Fifty-nine women with breast cancer will be included in each of the two groups. The study is powered to detect (α = .05, ß = .2) a medium effect size difference between the two groups (d = .5) in terms of patients' change in cognitive testing performances, from baseline until the end of the exercise-intervention. The cognitive test battery, recommended by the International Cancer and Cognition Task Force to assess CRCI, will be used as primary measure. This includes the Hopkins Verbal Learning Test (learning/verbal memory), the Controlled Oral Word Association Test (verbal fluency) and the Trail-Making-Test A/B (attention/set-switching). The following endpoints will be assessed as secondary measures: Go-/No-Go test performance (response inhibition), self-perceived cognitive functioning, serum levels of pro- and antiinflammatory markers (tumor necrosis factor alpha, Interleukin-6, Interleukin-1 alpha, Interleukin-1 beta, C-reactive protein, Interleukin-1 receptor antagonist and Interleukin-10), serum levels of neurotrophic and growth factors (brain-derived neurotrophic factor, insulin-like growth factor 1 and vascular endothelial growth factor), as well as common cancer-related side effects (decrease in physical capacity, fatigue, anxiety and depression, sleep disturbances, quality of life and chemotherapy compliance). DISCUSSION: This study will provide data on the question whether HIIT is an effective supportive therapy that alleviates CRCI in breast cancer patients. Moreover, the present study will help shed light on the underlying mechanisms of potential CRCI improving effects of exercise in breast cancer patients. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), ID: DRKS00011390 , Registered on 17 January 2018.

Effects of Kudiezi Injection on Serum Inflammatory Biomarkers in Patients with Acute Cerebral Infarction.

BACKGROUND: Kudiezi injection is a traditional Chinese medicine for acute cerebral infarction, but the exact mechanisms are poorly understood. OBJECTIVE: To investigate the mechanisms of Kudiezi injection on the inflammatory response in the treatment of acute cerebral infarction. METHODS: This was a prospective study of patients with acute cerebral infarction within 48 h of onset and treated between July 2012 and July 2016 at three hospitals in China. The patients were randomized to routine treatments (control group) versus routine treatments and Kudiezi injection (Kudiezi group). The National Institutes of Health Stroke Score was assessed on days 1, 3, 5, 7, and 14. The patients were tested for serum levels of pro- and anti-inflammatory cytokines (S100 calcium-binding protein B, neuron-specific enolase, interleukin-6, interleukin-10, interleukin-18, and matrix metaloproteinase-9; by enzyme-linked immunosorbent assay) immediately after admission and on days 3, 5, and 14. RESULTS: Stroke scores were improved in both groups from days 1 to 14. On days 5 and 7, stroke scores in the Kudiezi group were lower than in the control group (P < 0.05). Compared with controls, the Kudiezi group had lower serum S100 calcium-binding protein B on day 14; higher interleukin-6 and interleukin-10 on day 3; lower interleukin-6 and interleukin-18 on day 5; and lower interleukin-18 and matrix metaloproteinase-9 on day 14. CONCLUSION: Kudiezi injection could lead to early reduction of interleukin-6, interleukin-18, matrix metaloproteinase-9, neuron-specific enolase, and S100 calcium-binding protein B levels and increases of interleukin-10 levels in patients with acute ischemic stroke. This trial is registered with ClinicalTrials.gov NCT01636154.