Lower Levels Of TNF-α Research Articles

Casein fibres for wound healing.

The name casein is given to a family of phosphoproteins which is commonly found in milk. Until recently, this was a constituent of milk that was commonly discarded; however today, it is widely used in health supplements all over the world. In this work, a high loading (50 wt%) of casein is mixed with a solution of polycaprolactone (PCL) to produce bandage-like fibres with an average fibre diameter of 1.4 ± 0.5 µm, which would be used to cover wounds in a series of tests with diabetic rats. Mouse fibroblast cell viability tests show that the casein-loaded fibres had little cytotoxicity with over 90% observed viability. A 14-day in vivo trial involving three groups of rats, used as control (no treatment), pure PCL fibres and casein-loaded fibres, showed that the casein within the fibres contributed to a significantly more extensive healing process. Histological analysis showed increased development of granulation tissue and follicle regrowth for the casein-loaded fibres. Further analysis showed that casein-loaded fibres have significantly lower levels of TNF-α, TGF-β IL-1β, NF-κB and IL-6, contributing to superior healing. The results presented here show an economical and simple approach to advanced wound healing.

Atretic preovulatory follicles could be precursors of ovarian lutein cysts in the pig

Ovarian cysts contribute to reduced reproductive performance in pigs. Unfortunately, the mechanism of lutein cysts formation remains unknown. Here, we compared the endocrine and molecular milieus of intact, healthy preovulatory follicles (PF), gonadotropin (eCG/hCG)-induced healthy and atretic-like PF, as well as gonadotropin-provoked and spontaneous ovarian cysts in gilts. Several endocrine and molecular indicators and microRNA were compared in walls of PF and cysts. Intact and healthy PF, showed high estradiol/androstendione and low progesterone levels associated with CYP17A1, HSD17B1, and CYP19A1 elevation and reduced StAR/HSD3B1 protein expression. In contrast, low estradiol/androstendione and high progesterone concentrations, accompanied by decreased CYP17A1, HSD17B1, CYP19A1 and increased HSD3B1 protein abundance, appeared in atretic-like PF, gonadotropin-induced and spontaneous cysts. High progesterone receptor (PGR) protein abundance was maintained in intact and healthy PF, while it dropped in atretic-like PF, gonadotropins-induced and spontaneous cysts. The atretic PF showed high level of TNFα compared to healthy PF. In conclusion, follicular lutein cysts could be recruited from atretic-like PF with lost estrogenic milieu and inability to ovulate. Ovulatory cascade was presumably disrupted by a low PGR and high TNFα levels associated with earlier luteinization of follicular walls. These results suggest a novel mechanism of lutein ovarian cysts development in pigs and, perhaps, other species.

Evaluation of Certain Inflammatory Markers in Transfusion Dependent β-Thalassemic Patients

To determine the serum concentration of certain inflammatory markers including TNF-α and hs-CRPβ-thalassemic patients on different types of treatmentand to investigate the possible correlation between these inflammatory markers and iron overload referred to by serum ferritin concentration, moreoverto assesswhether inflammation in β-thalassemia could be controlled by deferasirox or deferoxamine as compared to transfusion dependent patients without iron chelator. Ninety transfusion dependent β-thalassemic children with age range 13–75 months were included in this study, and 30 age and sex matched healthy subjects served as control,thepatients were divided into three groups according to the type of the treatment,each group included 30 patients Group1 comprised β-thalassemic patients without iron chelator, Group2 comprisedβ-thalassemic patients on deferasirox iron chelator while Group3 comprisedβ-thalassemic patients on deferoxamine iron chelator. Serum ferritin, hs-CRP, and TNF-α was measured for all participants by ELISA method. Compared with the control, the serum level of ferritin and hs-CRP were significantly elevated in all patients groups while the serum level of TNF-α were only significantly elevated in Group1 and Group3. Further analysis of the results revealed positive correlation between serum ferritin withTNF-α and with hs-CRP.A comparison among the patients groups show that patients on deferasirox (Group2) had significantly low level of TNF-α as compared to Group1 and Group3. On the other hand serum ferritin and hs-CRP concentration in Group3 were significantly higher than the other two groups, furthermore when Group3 patients are subdivided according to their compliance on deferoxaminethe result show that the serum level of ferritin, hs-CRP and TNF-α are significantly higher in poor compliance subgroup as compared to good compliancepatients and when good compliance subgroup are compared with Group2 no significant deference in the measured parameter was found. Chronic inflammatory state is present in these patients withincreased levels of inflammatory markers such as TNF-α andCRP. The observed correlations of ferritin with inflammatory markers imply that iron overload may play a key role in release of these markers. Chelation Therapy with deferasirox can attenuate inflammation and reduces inflammatory markers level while deferoxamine appear to be less effective as most patients suffer from poor compliance on this type of iron chelator.

Tumour necrosis factor-alpha levels as predictor factor on clinical response of anthracycline-based neoadjuvant chemotherapy in locally advance breast cancer patients: experimental research.

Analysing TNF-α levels as a predictor factor on clinical response anthracycline-based neoadjuvant chemotherapy. This study design used observational analysis. The length of study was carried out in the period from May 2021 to June 2022. The study procedure included measuring participants' TNF-α levels the day before chemotherapy was carried out and clinical response. Participants received anthracycline-based neoadjuvant chemotherapy (cyclophosphamide of 500mg/m2, doxorubicin of 50mg/m2 and fluorouracil/5FU of 500mg/m2) for 3 cycles. The study analysis used the Chi-square, logistic regression and Spearman's test with P<0.05. The average TNF-α levels was 137.2±311.8pg/ml, ranging from 5.74 to 1.733pg/ml. The results of the calculation of the cutoff value of TNF-α in the study were 18635pg/ml (area under curve =0.850; 95% CI =0.729-0.971). Based on cutoff 1, most participants with high TNF-α levels also had a negative response of 83.3% and those with low TNF-α levels also had a positive response of 75% (P<0.001). Meanwhile, at cutoff 2, similar conditions were also found, namely high TNF-α levels, negative response (84.2%) and low TNF-α levels, positive response (78.9%; P<0.001). The statical analysis showed a significant association of TNF-α levels on the clinical response of chemotherapy, which showed r=-0.606 and P<0.001. TNF-α levels predict clinical response for anthracycline-based neoadjuvant chemotherapy in locally advanced breast cancer patients.

Effect of rumen protected methionine and choline supplementation on leukogram profile, oxidative stress, inflammatory and immunomodulatory responses of Surti buffaloes during transition period

Present study was conducted to observe effect of supplementing rumen protected methionine and choline on leukogram profile, oxidative stress, inflammatory and immunomodulatory responses during transition period in Surti buffaloes. Twenty-seven pregnant Surti buffaloes were selected and divided into three groups of nine animals each with following diet regime: Group I (Control)-basal diet, Group II (RPM)-basal diet+rumen protected methionine and Group III (RPM+RPC)-basal diet+rumen protected methionine+rumen protected choline. Supplementation of RPM @ 10 g/buffalo/day and RPC @ 50 g/buffalo/day was done from -15 d prepartum to 30 d postpartum. Blood samples were collected at start of experiment, 1st, 3rd and 6th week postpartum. At 1st and 3rd week postpartum, significantly higher level of GSH, SOD as well as TAS and lower level of LPO were observed in Group II and III as compared to control. Group III had highest SOD as well as TAS and lowest LPO levels. TNF-α and haptaglobin during postpartum period were significantly lower in Group II and III. Group III had lowest levels of TNF-α at 1st and 3rd week and haptoglobin at 1st, 3rd and 6th week postpartum. In vitro neutrophil phagocytic activity and lymphocyte proliferation were significantly higher in Group III followed by Group II and control during entire postpartum period. It was concluded that supplementation of rumen protected methionine and choline during transition phase of Surti buffaloes reduces oxidative stress as well as inflammatory tendencies and increases antioxidant status as well as immune response. Beneficial effects of supplementing both are more than supplementing rumen protected methionine alone.

Antibacterial-Anti-Inflammatory-Bone Restoration Procedure Achieved by MIN-Loaded PLGA Microsphere for Efficient Treatment of Periodontitis.

The main development process of periodontitis involves periodontal pathogenic bacteria as the initiating factor causing the onset of destructive inflammation, which in turn stimulates the destruction of periodontal tissue. It is difficult to achieve the eradication of periodontitis due to the complex interaction among antibacterial, anti-inflammatory, and bone restoration. Herein, we propose an antibacterial-anti-inflammatory-bone restoration procedural treatment strategy with minocycline (MIN) for the efficient treatment of periodontitis. In brief, MIN was prepared into PLGA microspheres with tunable release behavior using different species of PLGA, respectively. The optimally selected PLGA microspheres (LA:GA with 50:50, 10kDa, and carboxyl group) had a drug loading of 16.91%, an in vitro release of approximately 30days, which also had a particle size of approximately 11.8µm with a smooth appearance and a rounded morphology. The DSC and XRD results showed that the MIN was completely encapsulated in the microspheres as an amorphous state. Cytotoxicity tests demonstrated the safety and biocompatibility of the microspheres (cell viabilities at a concentration of 1-200μg/mL were greater than 97%), and in vitro bacterial inhibition tests showed that the selected microspheres could achieve effective bacterial inhibition at the initial stage after administration. The favorable anti-inflammatory (low TNF-α and IL-10 levels) and bone restoration effects (BV/TV: 71.8869%; BMD: 0.9782g/cm3; TB.Th: 0.1366mm; Tb.N: 6.9318mm-1; Tb.Sp: 0.0735mm) were achieved in a SD rat periodontitis model after administering once a week for four weeks. The MIN-loaded PLGA microspheres were proved to be an efficient and safe treatment for periodontitis by procedural antibacterial, anti-inflammatory, and bone restoration.

Genetic Arg-304-His substitution in GRK5 protects against sepsis progression by alleviating NF-κB-mediated inflammation

Previous studies have demonstrated that G protein-coupled receptor kinase 5 (GRK5) exerts a pivotal regulatory effect on the inflammation associated with sepsis. The present study aimed to investigate the clinical association of GRK5 genetic variants with sepsis and to further explore the underlying genetic mechanisms involved in regulating sepsis-induced inflammatory responses and the pathogenesis of sepsis. This case-control study enrolled 1081 septic patients and 1147 matched controls for genotyping of GRK5 rs2230349 and rs2230345 polymorphisms. The effect of these genetic variants on GRK5-mediated inflammatory responses was analyzed in peripheral blood mononuclear cells (PBMCs) and THP-1 macrophages. A clinically relevant polymicrobial sepsis model was established by subjecting wild-type (WT) and GRK5-knockout mice to cecal ligation and puncture (CLP) to evaluate the role of GRK5 in sepsis. We identified significant differences in the genotype/allele distribution of rs2230349 G>A, but not rs2230345, between the sepsis subtype and septic shock subgroups (GA+AA vs. GG genotype, OR=0.698, 95% CI=0.547-0.893, P=0.004; A vs. G allele, OR=0.753, 95% CI=0.620-0.919, P=0.005) and between the survivor and nonsurvivor subgroups (GA+AA vs. GG genotype, OR=0.702, 95% CI=0.531-0.929, P=0.015; A vs. G allele, OR=0.753, 95% CI=0.298-0.949, P=0.017). PBMCs carrying the sepsis-associated protective A allele produced significantly lower levels of TNF-α and IL-1β upon LPS stimulation. The results from the in vitro experiment showed that the Arg-304-His substitution caused by the rs2230349 G-to-A mutation in GRK5 significantly decreased the LPS-induced production of several proinflammatory cytokines, such as TNF-α, IL-6, IL-1β and MCP-1, via the IκB-α/NF-κB signaling pathway in THP-1 macrophages. Furthermore, GRK5-knockout mice exhibited a significant decrease in IκB-α phosphorylation/degradation, the p-p65/p65 ratio, the p-p50/p50 ratio, p65 nuclear translocation and downstream cytokine (TNF-α, IL-6, IL-1β and VCAM-1) production compared to WT mice after CLP surgery. A significant improvement in 7-day survival rate in GRK5-KO septic mice was observed in the presence of antibiotics. The Arg-304-His substitution caused by the rs2230349 G-to-A mutation in GRK5 might disrupt GRK5 function and alleviate IKB-α/NF-κB-mediated inflammatory responses, which ultimately conferred a genetic protective effect against susceptibility to sepsis progression and mortality. These results may, to some extent, explain the heterogeneity of the clinical prognoses of septic patients and provide novel opportunities for individualized approaches for sepsis treatment.

Dynamic Changes of Cytokine Profiles and Their Correlation With Tumor Recurrence Following Thermal Ablation in Hepatocellular Carcinoma.

The 5-year recurrence rate of thermal ablation for hepatocellular carcinoma (HCC) is high, and whether this treatment strategy induces systemic immune response remains elusive. This study aimed to investigate the effects of thermal ablation on HCC patients' cytokine profiles and to explore the correlation of cytokine profiles with tumor recurrence after ablation. A total of 22 HCC patients were included in this prospective study. The levels of 27 cytokines in the peripheral blood of HCC patients were measured before ablation (baseline), week 1, and week 4 after ablation using a Bio-Plex Pro Human Cytokine 27-plex Assay kit. Cytokines showed different dynamic changing trends after ablation treatment. It was found that the level of IL-6 was significantly elevated at week 1 and returned to the baseline level at week 4 after ablation. The level of IL-10 was slightly reduced at week 1 and significantly decreased at week 4. The levels of MCP-1, macrophage inflammatory protein-1β (MIP-1β), and TNF-α were similarly reduced at week 1 and increased at week 4. The levels of IL-17, platelet-derived growth factor-BB (PDGF-BB), and regulated upon activation, normal T cell expressed and secreted (RANTES) showed little to no change at week 1 while an observable increase at week 4. Patients with a high IL-10 level (2.99 pg/ml) at baseline and low levels of TNF-α (20.4 pg/ml), PDGF-BB (107.78 pg/ml), and RANTES (2303.94 pg/ml) at week 4 were at risk of tumor recurrence during 1-year follow-up. The results suggested that thermal ablation activated systemic immune responses by changing the levels of cytokines. The results also demonstrated that measurement of IL-10 at baseline, TNF-α, PDGF-BB, and RANTES at week 4 after ablation might predict the risk of tumor recurrence.

The impact of Lidocaine gel on TNF-α expression in surgically induced oral mucosal ulcers: an immunohistochemical analysis in rabbits

Background: Besides being a local anesthetic agent lidocaine is a promising anti-inflammatory agent with limited studies on its effect on the mucosa. Aim: Assess the anti-inflammatory effect of lidocaine following surgical induction wound in the oral mucosa as assessed by tumor necrosis factor-α (TNF-α) expression. Materials and methods: The study was conducted on 32 albino rabbits that were categorized into 2 equal groups of 16 rabbits: In the control group an oral wound was surgically induced and left without treatment and in the treatment group an oral wound was surgically induced and received topical Lidocaine gel. Euthanasia of animals was carried out on days 1, 3, 7, and 10, and sample sites were processed for histopathological and immunohistochemical staining for TNF-α. Results: In the histological observations, it was noticed that the healing process was more rapid and convenient in the test group compared to the control group. For Immunohistochemical assessment, the TNF-α started to express clearly at 1 day and gradually decreased and disappeared at 10 days with a superior effect of the lidocaine group over the control group. Conclusion: Lidocaine seems to have anti-inflammatory reactions by lowering TNF-α levels and preventing the production of pro-inflammatory cytokines.

The effects of glucocorticoid plus intravenous immunoglobulin (IVIG) vs IVIG alone on platelet activation in children with Kawasaki disease.

Even though intravenous immunoglobulin (IVIG) is a current treatment for Kawasaki disease (KD), 10-20% of patients require additional therapy. This study seeks to investigate the therapeutic effects of glucocorticoids plus IVIG on KD and to ascertain the subsequent effect on platelet activation during the acute phase. A total of 32 children with KD were randomly classified into two groups: the experimental group (16 cases) and the control group (16 cases). The control group was exposed to IVIG (2 g/kg), whereas children in the experimental group were treated with IVIG (2 g/kg) + glucocorticoid. Peripheral venous blood samples were obtained from all participants before treatment as well as three days post-treatment to test platelet activation levels with procaspase activating compound-1 (PAC-1) antibody, Toll-like receptor 4 (TLR4), interleukin-6 (IL- 6), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), and C-reactive protein (CRP). Fever duration posttreatment was documented for both groups. Additionally, the coronary arteries in both groups were evaluated during three months of treatment. After treatment, the experimental group had remarkably lower levels of TNF-α, CRP, PCT, IL-6, PAC- 1, and TLR4 relative to the control group. The fever persistence rate was considerably elevated in the control group compared to the experimental group (log-rank, P=0.024). In addition, the z-score of coronary artery size dropped after IVIG + glucocorticoids treatment compared to the control group, although this difference was not significant. The IVIG + glucocorticoids can quickly mitigate the inflammatory response and platelet activation. Moreover, it can also improve clinical symptoms in children with KD.

The usage of orally gavage and topically applied omega -3 in the treatment of experimental gingivitis in rats.

Abstract&#x0D; Aim of the study: This study aimed to evaluate effects of omega 3 polyunsaturated fatty acids on ligation induced gingivitis in rats through the immunological analysis for rat’s gingival tissue level of tumor necrotic factor-α( TNF-α) .&#x0D; Materials and methods: The gingivitis was induced for rats by ligation around lower central incisors. Fifty animals with the induced gingivitis were divided into: five animals were sacrificed at the first day after removal of ligature, and fifteen animals as positive control group. Fifteen animals were used as 1st treatment group with orally gavage omega 3 polyunsaturated fatty acid and fifteen animals as 2nd treatment groups with topically applied omega3 a Five animals were used as negative control groups (-ve) group.&#x0D; Animals were sacrificed and tissue sections were evaluated for Tumor necrotic factor –α (TNF-α) levels, this biomarker were measured by ELISA method for four times, first after ligation removal (day zero), three days, one week and two weeks for immunological analysis.&#x0D; Results: The result showed that level of TNF-α were significantly lower in systemic treatment groups in comparison with positive control groups in all duration of study, and there were significant difference between topical treatment groups on the 3rd and 7th days and no significant differences on the 14th day after removal of ligature in comparison with (+ve) ,also there was no significant&#x0D; difference between these two treatment groups in all duration of study. T-test used for statistical analyses, with p&lt;0.05 regarded as significant and p&gt; 0.001 as high significant.&#x0D; Conclusion: orally gavage and topical application of omega-3 FAs is effective treatment for reduction of inflammation in gingivitis, resulting in lower level of TNF-α.

Hcp1-loaded staphylococcal membrane vesicle vaccine protects against acute melioidosis.

Burkholderia pseudomallei is the causal agent of melioidosis, a deadly tropical infectious disease that lacks a vaccine. On the basis of the attenuated Staphylococcus aureus RN4220-Δagr (RN), we engineered the RN4220-Δagr/pdhB-hcp1 strain (RN-Hcp1) to generate B. pseudomallei hemolysin-coregulated protein 1 (Hcp1)-loaded membrane vesicles (hcp1MVs). The immunization of BALB/c mice with hcp1MVs mixed with adjuvant by a three-dose regimen increased the serum specific IgG production. The serum levels of inflammatory factors, including TNF-α and IL-6, in hcp1MV-vaccinated mice were comparable with those in PBS-challenged mice. The partial adjuvant effect of staphylococcal MVs was observed with the elevation of specific antibody titer in hcp1MV-vaccinated mice relative to those that received the recombinant Hcp1 protein (rHcp1) or MVs derived from RN strain (ΔagrMVs). The hcp1MVs/adjuvant vaccine protected 70% of mice from lethal B. pseudomallei challenge. Immunization with hcp1MVs only protected 60% of mice, whereas vaccination with rHcp1 or ΔagrMVs conferred no protection. Moreover, mice that received hcp1MVs/adjuvant and hcp1MVs immunization had low serum TNF-α and IL-6 levels and no inflammatory infiltration in comparison with other groups. In addition, all surviving mice in hcp1MVs/adjuvant and hcp1MVs groups exhibited no culturable bacteria in their lungs, livers, and spleens five days postinfection. Overall, our data highlighted a new strategy for developing B. pseudomallei vaccine and showed that Hcp1-incorporated staphylococcal MV is a promising candidate for the prevention of acute melioidosis.

Effects of Bdellovibrio bacteriovorus HD100 on experimental periodontitis in rats.

The aim of this study was to evaluate the effects of Bdellovibrio bacteriovorus HD100 on experimental periodontitis (EP) in rats. Thirty-two rats were divided into four groups: control, C-HD100 (B. bacteriovorus), EP, and EP-HD100. On day 0, EP was induced by the placement of cotton ligatures around the mandibular first molars (MFMs) in the EP and EP-HD100 groups. In the C-HD100 and EP-HD100 groups, suspensions containing 1×109 PUF/ml of B. bacteriovorus HD100 were topically administered to the subgingival region of MFMs on days 0, 3, and 7. Animals were euthanized on day 14. Morphometrics analyses were performed in hemimandibles. The levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, IL-10, IL-1β, transforming growth factor beta (TGF-β), macrophage colony-stimulating factor (M-CSF) and regulated on activation and normal T cell expressed and secreted (RANTES) were determined by enzymatic immunoassays in gingival tissues. Beta defensin (BD)-1, BD-2, and BD-3, Toll-like receptors (TLR)-2 and TLR-4, and a cluster of differentiation (CD)-4, CD-8 and CD-57 were analyzed by immunohistochemistry in hemimandibles. Data were statistically analyzed. The EP group showed greater alveolar bone loss than EP-HD100 (p<.05). The EP-HD100 group showed higher levels of MCP-1, RANTES, IL-10, and TGF-β, lower levels of TNF-α than the EP group (p<.05). No differences were observed in IL-1β, IL-6, and M-CSF levels between EP and EP-HD100 groups. The C-HD100 group had higher IL-6, TNF-α, RANTES, and MCP-1 levels than the control group (p<.05). Regarding BD, the EP-HD100 group showed a larger immunolabeling pattern for BD-1, BD-2, and BD-3 than the EP group (p<.05). No significant differences in the immunolabeling pattern were observed for TLR-2, TLR-4, CD-4, CD-8, and CD-57 between EP and EP-HD100 groups. The topical use of B. bacteriovorus HD100 reduces alveolar bone loss, increases expression of BD, and modulates the cytokines levels on periodontal tissues in rats with EP.

Detoxification of LTA by intracanal medication: analysis by macrophages proinflammatory cytokines production.

The aim of this study was to evaluate in vitro the effect of calcium hydroxide [Ca(OH)2], 2% chlorhexidine gel (CHX) on macrophages (RAW 264.7) to produce pro-inflammatory cytokines and nitric oxide after pretreatment with lipoteichoic acid (LTA) of Enterococcus faecalis. Forty-eight human single-rooted teeth were instrumented with R25.08 (RECIPROC) and sterilized by gamma irradiation. LTA was inoculated in the root canal of each specimen for 96 hours. Specimens were instrumented with 40.06 and 50.05 (RECIPROC) and medicated with: I) Pyrogen-free saline solution (SS); II) 2% CHX gel; III) Ca(OH)2 + SS; or IV) Ca(OH)2 + CHX for 14 days. Three samples (S) were performed of the root canal of each specimen at: S1) immediately after instrumentation; S2) after Ethylenediaminetetraacetic acid (EDTA); S3) after intracanal medication removal. Subsequent quantification of cytokines (IL-1β, TNF-α, MIP-1α, IP-10, G-CSF and IL-6) by immunosorbent assay (ELISA) and nitric oxide by the Griess method was carried-out. Data were submitted to a normality test and then analyzed with one-way ANOVA and Tukey test with a significance level of 5% using GraphPad Prism 6. Ca(OH)2 + SS and Ca(OH)2 + CHX presented lower levels of TNF-α, TNF-α, IL-6, G-CSF and nitric oxide. Ca(OH)2 + SS was the most effective in reducing MIP-1α. CHX was effective in reducing IL-6 and G-CSF. Therefore, the combined intracanal medication of calcium hydroxide and chlorhexidine is effective in reducing the cytokines TNF-α, IL-1β, IL-6, G-CSF and nitric oxide.

Association between serum TNF-α level with the incidence of metastases in women with breast cancer in Dr. Soetomo General Hospital, Indonesia

Abstract Background: Breast cancer is the most common cancer in women. The occurrence of metastasis in breast cancer should be detected early. Tumor necrosis factor-α (TNF-α) is involved in every step of the carcinogenesis process. A rise in TNF-α level is linked to the advancement of breast cancer. We aimed to determine the association between TNF-α levels and breast cancer metastases. Methods: An analytic cross-sectional study was conducted on women with breast cancer treated at the Oncology Surgery Center between November 2021 and April 2022. The patient's data were collected from the medical record, including age, menopausal status, tumor size and lymph node involvement, and tumor subtype. The serum TNF-α level was measured using ELISA. The optimal cut-off value was determined using the receiver operating characteristics analysis. The association between serum TNF-α and the incidence of breast cancer metastases was analyzed using SPSS version 26 for Windows. Results: We analyzed a total of 50 patients. The mean age was 48.8 ± 8.3 years. The serum TNF-α level was divided into high-TNF-α and low-TNF-α using a cut-off value of 22.755 pg/mL. There were 27 patients (27/50; 54.0%) with high serum TNF-α levels and 23 patients (23/50; 46.0%) with low TNF-α levels. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 73.9%, 63.0%, 63,0%, 73,9%, and 68%, respectively. There was a statistically significant association between serum TNF-α levels and metastatic breast cancer (p=0.009). Conclusion: There was a significant association between TNF-α levels and metastatic breast cancer. Serum TNF-α may be a potential biomarker to detect metastasis in breast cancer patients.

Clinical characteristics and short-term recovery of hyposmia in hospitalized non-severe COVID-19 patients with Omicron variant in Shanghai, China.

Olfactory dysfunction is a common neurological symptom of Corona Virus Disease 2019(COVID-19). Little is known about hyposmia after COVID-19 infection with Omicron variant in Chinese population. To investigate the incidence, clinical characteristics and recovery of hyposmia in hospitalized non-severe COVID-19 patients with Omicron variant in Shanghai, China. Three hundred and forty-nine Chinese non-severe COVID-19 patients with Omicron variant were consecutively enrolled in a designated hospital to investigate the incidence of hyposmia in hospitalization and the recovery rate 1 month later. The visual assessment scale (VAS) was used to evaluate the severity of hyposmia. We compared the demographic, clinical features and treatment outcomes, as well as laboratory parameters between patients with and without hyposmia. The cross-sectional survey showed that 22 (6.3%) hospitalized patients with non-severe COVID-19 had hyposmia. Patients with hyposmia were younger (61.5 vs. 72.0, p = 0.002), had more related clinical symptoms (sore throat, cough, poor appetite, diarrhea, myalgia and taste impairment, etc.), a higher proportion of moderate clinical type (31.8 vs. 13.5%, p = 0.028) and longer duration of hospitalization (11 vs. 8 days, p = 0.027) than those without hyposmia. Whereas, there were no significant differences regarding gender, comorbidity and nucleic acid conversion time between the two groups. Laboratory subgroup analyses demonstrated that patients with hyposmia had slightly low serum IL-6 and TNF-α levels. However, both of the levels were not associated with hyposmia occurrence in multivariate regression analyses. Further follow-up study disclosed that 16 of 22 (72.7%) hyposmia patients had recovered olfaction 1 month later. Serum IL-6 and TNF-α levels were similar between hyposmia recovered patients and those with persistent hyposmia. Although the incidence of hyposmia after Omicron variant infection is relatively low and the short-term recovery rate is quite high, patients with hyposmia are prone to have a higher proportion of both upper and lower respiratory tract involvements, gastrointestinal and neurological symptoms, contributing to a longer duration of hospitalization.

Brain protection by transamniotic stem cell therapy (TRASCET) in a model of intrauterine growth restriction (IUGR)

PurposeTransamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) has been shown experimentally to reverse some of the effects of intrauterine growth restriction (IUGR), apparently by attenuating placental inflammation. Neurodevelopmental deficits driven by neuroinflammation are major complications of IUGR. We sought to determine whether MSC-based TRASCET also mitigates inflammation in the fetal brain. MethodsPregnant Sprague-Dawley dams (n = 8) were exposed to alternating 12-hour hypoxia (10.5% O2) cycles from gestational day 15 (E15) until term (E21). One group remained untreated (n = 28 fetuses). Three groups received volume-matched intra-amniotic injections into all fetuses (n = 72) of either saline (sham; n = 19), or a suspension of amniotic fluid-derived MSCs, either in native state (TRASCET; n = 20), or primed by exposure to interferon-gamma (IFN-γ) and interleukin-1beta (IL-1β) for 24 h prior to administration in vivo (TRASCET-Primed; n = 29). Donor MSCs were syngeneic Lewis rat cells phenotyped by flow cytometry. Normal fetuses served as controls (n = 20). Multiple analyses were performed at term, including ELISA in fetal brains for the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and IL-1β. Statistical comparisons were by Wilcox-rank sum test, including Bonferroni-adjusted significance. ResultsOverall survival was 75% (88/116). Gross brain weights were significantly decreased from normal in both the untreated and sham groups (both p<0.001) and significantly increased in both TRASCET groups when compared to untreated and sham (p = 0.003 to <0.001). TRASCET-Primed led to significantly lower levels of TNF-α and IL-1β compared to untreated (both p<0.001) and sham (p = 0.017 and p = 0.011, respectively). Non-primed TRASCET led to significantly lower levels of TNF-α and IL-1β compared to untreated (p = 0.009 to <0.001), but not sham (p = 0.133 and p = 0.973, respectively). ConclusionsTransamniotic stem cell therapy with primed mesenchymal stem cells reverses some of the central nervous system effects of intrauterine growth restriction in a rat model, possibly by modulating neuroinflammation. Type of StudyAnimal and laboratory study. Level of EvidenceN/A (animal and laboratory study).

Brazilian organic propolis for prevention and treatment of radiation-related oral acute toxicities in head and neck cancer patients: A double-blind randomized clinical trial.

Background: Oral mucositis (OM) is one of the most important acute toxicities from radiotherapy (RT) in head and neck cancer patients and can impair oncologic treatment. Dysphagia, dysgeusia, pain, and oral candidiasis are other common toxicities. Brazilian Organic Propolis (BOP) is a recently described propolis variant and BOP types 4 and 6 have shown important antioxidant, anti-inflammatory, and antifungal properties. Purpose: To investigate the use of BOP as a preventive and/or complementary therapeutic option for radiotherapy-induced oral mucositis, dysphagia, dysgeusia, pain, and oral candidiasis. Additionally, proinflammatory cytokines were assessed to investigate their anti-inflammatory role. Methods: Sixty patients were included in this randomized, double-blind, controlled clinical trial. Patients were randomized to receive either aqueous suspension of a BOP or placebo throughout RT. Also, all patients underwent low-level laser therapy as routine oral care. OM, dysphagia, and dysgeusia were assessed weekly according to WHO and NCI scales. Pain-related to OM was assessed according to a Visual Analog Scale and the presence or absence of oral candidiasis was checked by intraoral examination. Protein levels of TNF-α and IL-1β from oral mucosa were assessed by ELISA. Results: Patients in the propolis group had a lower mean score of OM, dysphagia, dysgeusia, and most patients reported moderate pain. Fewer patients developed oral candidiasis in the propolis group, and the number of episodes was lower among patients that used BOP (p < 0.05). In addition, the BOP group presented significantly lower levels of IL-1β since the beginning of treatment when compared with placebo patients (p < 0.05) and a lower level of TNF-α at the end of treatment (p < 0.001). Conclusion: Topic use of BOP reduced TNF-α and IL-1β levels, oral candidiasis episodes, and seems to be a useful complementary option for the prevention and treatment of the main acute oral toxicities of RT. Clinical Trial Registration: http://www.ensaiosclinicos.gov.br/rg/RBR-9f8c78/, identifier RBR-9f8c78

Wenshen-Jianpi prescription, a Chinese herbal medicine, improves visceral hypersensitivity in a rat model of IBS-D by regulating the MEK/ERK signal pathway.

The goal of the study was to analyze whether WJP can alleviate visceral hypersensitivity in IBS-D model rats. In this study, 36 Sprague–Dawley (SD) rats aged 4 weeks old were randomly divided into two groups: the model group (n = 27) and the control group (n = 9). The rat model of IBS-D was established by modified compound methods for 4 weeks. After the modification, IBS-D rats were randomly divided into three groups, namely, the IBS-D model group (n = 9), the positive drug group (n = 9), and the WJP group (n = 9), with different interventions, respectively. The control group was fed and allowed to drink water routinely. The Bristol stool scale scores were used to assess the severity of diarrhea. Abdominal withdrawal reflex (AWR) scores were used to assess visceral sensitivity. Expression of TNF-α was measured, and histopathological examinations were performed to assess colon inflammation in IBS-D model rats. Key factors of the MEK/ERK signal pathway in the tissue of the colon and hippocampus were measured to analyze the mechanism of WJP. Compared with the control group, the Bristol stool scale scores in the model group were significantly increased (p < 0.0001). The scores of the WJP group were significantly decreased compared with the model group (p = 0.0001). Compared with the control group, AWR scores in the model group at each pressure level were significantly increased (p = 0.0003, p < 0.0001, p = 0.0007, and p = 0.0009). AWR scores of the WJP group were significantly decreased compared with the model group (p = 0.0003, p = 0.0007, p = 0.0007, and p = 0.0009). Compared with the control group, the model group had significantly higher expression of TNF-α in the colon tissue (p < 0.0001). However, the WJP group had significantly lower level of TNF-α compared with the model group (p < 0.0001). Meanwhile, compared with the control group, the relative expression of the proteins of p-MEK1/2, p-ERK1, and p-ERK2 in the colon tissue was significantly increased in the model group (p < 0.0001). Compared with the model group, the relative expression of the proteins in the colon tissue were significantly decreased in the WJP group (p < 0.0001, p = 0.0019, and p = 0.0013). Compared with the control group, the relative expression of the proteins of p-MEK1/2, p-ERK1, and p-ERK2 in the hippocampus tissue were significantly increased in the model group (p < 0.0001). Compared with the model group, the relative expression of the proteins in the hippocampus tissue were significantly decreased in the WJP group (p = 0.0126, p = 0.0291, and p = 0.0145). The results indicated that WJP can alleviate visceral hypersensitivity in IBS-D model rats, possibly mediated by downregulating the expression of TNF-α, p-MEK1/2, p-ERK1, and p-ERK2 in the colon tissue. At the same time, WJP also affects downregulating the expression of p-MEK1/2, p-ERK1, and p-ERK2 in the hippocampus tissue.

Potential Protective Role of Galectin-3 in Patients with Gonarthrosis and Diabetes Mellitus: A Cross-Sectional Study.

Background: Gonarthrosis and diabetes mellitus are two diseases that are increasingly being linked. The aim of this study was to quantify serum levels of Gal-3, pro- and anti-inflammatory cytokines (including their ratios and correlations), and participant’s condition (pain, stiffness, functional limitations) in gonarthrosis patients with and without diabetes mellitus. Methods: A between-subject, cross-sectional experimental design was adopted. Serum levels of TNF-α, IL-6, IL-12, IL-23, IFN-γ, IL-17, IL-10, Gal-3, and WOMAC score were measured. Results: Gonarthrosis patients with diabetes mellitus had significantly (p < 0.05) lower levels of TNF-α, IL-6, IL-12, IL-17, IFN-γ, and Gal-3 compared to gonarthrosis patients without diabetes mellitus. On the other hand, IL-10/TNF-α, IL-10/IL-6, IL-10/IL-12, Gal-3/TNF-α, Gal-3/IL-6, and Gal-3/IL-12 (p = 0.001) were significantly higher (p < 0.05) in gonarthrosis with diabetes mellitus. Moderate–large correlation (p < 0.05) was detected between the serum values of Gal-3 and pro- and anti-inflammatory cytokines, including IL-12 (r = 0.575), IL-10 (r = 0.535), TNF-α (r = 0.306), and IL-23 (r = 0.323). WOMAC index was significantly lower (p < 0.05) in gonarthrosis patients without diabetes mellitus compared to gonarthrosis patients with diabetes mellitus. Conclusions: Correlation between Gal-3 and proinflammatory cytokines and its dominance over proinflammatory cytokines implicate the potential role of Gal-3 in preventing cartilage destruction.