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Zhongguo Zhong Yao Za Zhi = Zhongguo... Mar 2024Network pharmacology was employed to probe into the mechanism of Fushen Granules in treating peritoneal dialysis-rela-ted peritonitis(PDRP) in rats. The main active...
Network pharmacology was employed to probe into the mechanism of Fushen Granules in treating peritoneal dialysis-rela-ted peritonitis(PDRP) in rats. The main active components of Fushen Granules were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their targets were predicted. PDRP-related targets were retrieved from DisGeNET and other databases. The common targets shared by the drug and the disease were identified by the online tool, and protein-protein interaction(PPI) network of the common targets. The obtained 276 common targets were imported into DAVID for GO function enrichment and KEGG pathway enrichment. The main signaling pathway of Fushen Granules in the treatment of PDRP was predicted as Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB. The rat model of uremia was induced by 5/6 nephrectomy. From two weeks after operation, the rat model of peritoneal dialysis(PD) was established by intraperitoneal injection of 20 mL dialysate with 1.25% glucose every day. The sham operation group and model group received 2 mL normal saline by gavage every day. The rats in Fushen Gra-nules groups were administrated with 2 mL solutions of low-(0.54 g·kg~(-1)), medium-(1.08 g·kg~(-1)) and high-dose(2.16 g·kg~(-1)) Fushen Granules every day. The bifico group received 2 mL(113.4 mg·kg~(-1)) of bifico solution every day. At the end of the 8th week, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in each group were measured. The serum levels of hypersensitive C reactive protein(hs-CRP), tumor necrosis factor(TNF)-α, and interleukin(IL)-6 were measured, and the pathological changes in the colon tissue were observed by hematoxylin-eosin(HE) staining. The serum levels of lipopolysaccharide(LPS) and lipopolysaccharide-binding protein(LBP) of rats were measured, and the expression levels of LBP, TLR4, NF-κB p65, inhibitor of κB kinase α(IκBα), TNF-α, and IL-1β in the colon tissue were determined. Compared with sham operation group, the model group had abnormal structure of all layers of colon tissue, sparse and shorter intestinal villi, visible edema in mucosal layer, wider gap, obvious local inflammatory cell infiltration, significantly decreased body weight(P<0.01), and significantly increased kidney function index(Scr, BUN) content(P<0.01). Serum levels of inflammatory cytokines(hs-CRP, TNF-α, IL-6), LPS and LBP were significantly increased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1β were significantly increased(P<0.01), and protein expressions of IκBα were significantly decreased(P<0.01). Compared with model group, intestinal villi damage in colonic tissue of rats in low-, medium-and high-dose Fushen Granules groups and bifico group were alleviated to different degrees, edema in submucosa was alleviated, space was narrowed, and inflammatory cell infiltration in lamina propria was reduced. The contents of renal function index(Scr, BUN) and serum inflammatory factors(hs-CRP, TNF-α, IL-6) were significantly decreased(P<0.05 or P<0.01) in medium-and high-dose Fushen Granules groups and bifico group(P<0.05 or P<0.01). Serum LPS and LBP contents in Fushen Granules group and bifico group were significantly decreased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1β in Fushen Granules group were significantly decreased(P<0.05 or P<0.01), and protein expressions of IκBα were significantly increased(P<0.01). The expression of LBP protein in bifico group was significantly decreased(P<0.01). The results suggest that Fushen Granules can protect the residual renal function of PD rats, reduce the inflammatory response, and protect the colon tissue. Based on network pharmacology, TLR4/NF-κB pathway may be the main signaling pathway of Fushen granule in the treatment of PDRP. The results showed that Fushen Granules could improve intestinal inflammation and protect intestinal barrier to prevent PDRP by regulating the expression of key factors in TLR4/NF-κB pathway in colon of PD rats.
Topics: Rats; Animals; NF-kappa B; NF-KappaB Inhibitor alpha; Network Pharmacology; Tumor Necrosis Factor-alpha; C-Reactive Protein; Toll-Like Receptor 4; Interleukin-6; Lipopolysaccharides; Animal Experimentation; Peritonitis; Peritoneal Dialysis; Edema
PubMed: 38621947
DOI: 10.19540/j.cnki.cjcmm.20231210.503 -
International Journal of Molecular... Mar 2024KH-type splicing regulatory protein (KSRP) is a single-stranded nucleic acid-binding protein with multiple functions. It is known to bind AU-rich motifs within the...
KH-type splicing regulatory protein (KSRP) is a single-stranded nucleic acid-binding protein with multiple functions. It is known to bind AU-rich motifs within the 3'-untranslated region of mRNA species, which in many cases encode dynamically regulated proteins like cytokines. In the present study, we investigated the role of KSRP for the immunophenotype of macrophages using bone marrow-derived macrophages (BMDM) from wild-type (WT) and KSRP mice. RNA sequencing revealed that KSRP BMDM displayed significantly higher mRNA expression levels of genes involved in inflammatory and immune responses, particularly type I interferon responses, following LPS stimulation. In line, time kinetics studies revealed increased levels of interferon-γ (IFN-γ), interleukin (IL)-1β and IL-6 mRNA in KSRP macrophages after 6 h subsequent to LPS stimulation as compared to WT cultures. At the protein level, KSRP BMDM displayed higher levels of these cytokines after overnight stimulation. Matching results were observed for primary peritoneal macrophages of KSRP mice. These showed higher IL-6, tumor necrosis factor-α (TNF-α), C-X-C motif chemokine 1 (CXCL1) and CC-chemokine ligand 5 (CCL5) protein levels in response to LPS stimulation than the WT controls. As macrophages play a key role in sepsis, the in vivo relevance of KSRP deficiency for cytokine/chemokine production was analyzed in an acute inflammation model. In agreement with our in vitro findings, KSRP-deficient animals showed higher cytokine production upon LPS administration in comparison to WT mice. Taken together, these findings demonstrate that KSRP constitutes an important negative regulator of cytokine expression in macrophages.
Topics: Animals; Mice; Carrier Proteins; Interleukin-6; Lipopolysaccharides; Macrophages; Cytokines; 3' Untranslated Regions
PubMed: 38612694
DOI: 10.3390/ijms25073884 -
International Journal of Molecular... Mar 2024Endometriosis is a complex gynecological disease that affects more than 10% of women in their reproductive years. While surgery can provide temporary relief from women's...
Endometriosis is a complex gynecological disease that affects more than 10% of women in their reproductive years. While surgery can provide temporary relief from women's pain, symptoms often return in as many as 75% of cases within two years. Previous literature has contributed to theories about the development of endometriosis; however, the exact pathogenesis and etiology remain elusive. We conducted a preliminary investigation into the influence of primary endometrial cells (ECs) on the development and progression of endometriosis. In vitro studies, they were involved in inducing Lipopolysaccharide (LPS) in rat-isolated primary endometrial cells, which resulted in increased nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) mRNA gene expression (quantitative polymerase chain reaction analysis, qPCR) and protein expression (western blot analysis). Additionally, in vivo studies utilized autogenic and allogeneic transplantations (rat to rat) to investigate endometriosis-like lesion cyst size, body weight, protein levels (immunohistochemistry), and mRNA gene expression. These studies demonstrated that estrogen upregulates the gene and protein regulation of cytoskeletal (CK)-18, transforming growth factor-β (TGF-β), VEGF, and tumor necrosis factor (TNF)-α, particularly in the peritoneum. These findings may influence cell proliferation, angiogenesis, fibrosis, and inflammation markers. Consequently, this could exacerbate the occurrence and progression of endometriosis.
Topics: Female; Humans; Animals; Rats; Endometriosis; Vascular Endothelial Growth Factor A; Cell Proliferation; Cytoskeleton; RNA, Messenger
PubMed: 38612685
DOI: 10.3390/ijms25073873 -
Frontiers in Immunology 2024Excessive salt intake is a widespread health issue observed in almost every country around the world. A high salt diet (HSD) has a strong correlation with numerous...
Excessive salt intake is a widespread health issue observed in almost every country around the world. A high salt diet (HSD) has a strong correlation with numerous diseases, including hypertension, chronic kidney disease, and autoimmune disorders. However, the mechanisms underlying HSD-promotion of inflammation and exacerbation of these diseases are not fully understood. In this study, we observed that HSD consumption reduced the abundance of the gut microbial metabolite L-fucose, leading to a more substantial inflammatory response in mice. A HSD led to increased peritonitis incidence in mice, as evidenced by the increased accumulation of inflammatory cells and elevated levels of inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and monocyte chemotactic protein-1 (MCP-1, also known as C-C motif chemokine ligand 2 or CCL2), in peritoneal lavage fluid. Following the administration of broad-spectrum antibiotics, HSD-induced inflammation was abolished, indicating that the proinflammatory effects of HSD were not due to the direct effect of sodium, but rather to HSD-induced alterations in the composition of the gut microbiota. By using untargeted metabolomics techniques, we determined that the levels of the gut microbial metabolite L-fucose were reduced by a HSD. Moreover, the administration of L-fucose or fucoidan, a compound derived from brown that is rich in L-fucose, normalized the level of inflammation in mice following HSD induction. In addition, both L-fucose and fucoidan inhibited LPS-induced macrophage activation . In summary, our research showed that reduced L-fucose levels in the gut contributed to HSD-exacerbated acute inflammation in mice; these results indicate that L-fucose and fucoidan could interfere with HSD-promotion of the inflammatory response.
Topics: Mice; Animals; Sodium Chloride, Dietary; Fucose; Inflammation; Diet; Polysaccharides
PubMed: 38596683
DOI: 10.3389/fimmu.2024.1333848 -
Clinical Case Reports Apr 2024Gallbladder volvulus (GV) is a medical emergency and a rare cause of acute abdominal pain among the pediatric population. GV is more prominent usually in boys in...
Gallbladder volvulus (GV) is a medical emergency and a rare cause of acute abdominal pain among the pediatric population. GV is more prominent usually in boys in pediatric patients. If it is not diagnosed and surgically intervened promptly, GV will become a life-threating condition. Fortunately, a safe and effective laparoscopic cholecystectomy is now widely indicated. A 5 years old female patient with abdominal pain and heavy much vomiting was referred to the emergency room in our hospital. She was suspiciously diagnosed with acute inflammation of the gallbladder according to the results of abdominal ultrasound and computerized tomography (CT) scan already performed on admission. One day after the hospitalization, abdominal ultrasound, and CT scan were performed again because of intensification of her abdominal pain and revealed the clinical portrait of GV such as a "floating gallbladder" sign, an echogenic cone structure, an elongated axis displaced horizontally instead of vertically and a lack of intramural blood flow. The acute GV diagnosis was made and the patient was operated, using the laparoscopic cholecystectomy on time, the gallbladder was tightly twisted clockwise at approximately 720°. The operation and postoperative treatment went quite well and the patient was discharged from the hospital on postoperative Day 7. GV is very rare in children, easily omitted or misdiagnosed with cholecystitis. Imaging diagnosis such as ultrasound, CT with contrast helps make diagnosis promptly that avoids severe complications such as gallbladder perforation, necrosis, and biliary peritonitis.
PubMed: 38590331
DOI: 10.1002/ccr3.8743 -
Pharmacology Apr 2024Traditionally and empirically, Hibiscus sabdariffa L. have been used in treating diabetes mellitus due to their antioxidant activity. This study aims to investigate the...
INTRODUCTION
Traditionally and empirically, Hibiscus sabdariffa L. have been used in treating diabetes mellitus due to their antioxidant activity. This study aims to investigate the effect of administering the ethyl acetate fraction of hibiscus calyxes on malondialdehyde (MDA) levels, Tumor Necrosis Factor-α (TNF-α) levels, bleeding time, and platelet count in male white rats induced with streptozotocin-induced diabetes.
METHOD
Thirty-six Wistar Kyoto rats were induced with intra-peritoneal streptozotocin at 55 mg/kg BW and stabilized for five days to obtain diabetic conditions. Diabetic animals were divided into four groups; the diabetic group was given vehicle, the glibenclamide group was given 0.45 mg/kg BW of Glibenclamide, and two groups were administered the ethyl acetate fraction of hibiscus calyxes (EAFHC) at doses of 100 mg/kg BW and 200 mg/kg BW for five days. Subsequently, the MDA, TNF-α, bleeding time and platelet count levels were examined on days 1, 3, and 5, respectively. All data were analyzed using two-way ANOVA followed by the Duncan Multiple Rank Test (DMRT).
RESULTS
EAFHC significantly reduced MDA and TNF-α levels (p<0.05). Additionally, this fraction appeared to shorten bleeding time and decrease platelet count in diabetic rats. Administration of the EAFHC for five days effectively lowered MDA and TNF-α levels significantly, decreased platelet counts and prolonged coagulation (p<0.05) in diabetic rats.
CONCLUSION
This study demonstrates that EAFHC effectively reduces MDA and TNF-α levels and reduces the risk of hypercoagulability in diabetic model.
PubMed: 38583417
DOI: 10.1159/000538362 -
Hernia : the Journal of Hernias and... Apr 2024Large abdominal wall hernias often require techniques for wall expansion to improve surgical outcomes. The peritoneal flap hernioplasty (PF) is one such technique that...
INTRODUCTION
Large abdominal wall hernias often require techniques for wall expansion to improve surgical outcomes. The peritoneal flap hernioplasty (PF) is one such technique that utilizes the hernia sac to reconstruct the abdominal wall, however, with limited published data. It is a modification of the Rives-Stoppa mesh repair where a part of the bisected hernia sac is utilized to reconstruct the anterior fascia and the other part for the posterior fascia. We present a collated retrospective analysis of the outcomes from three centers performing PF with or without transverse abdominis release (TAR) in patients with complex ventral hernias.
METHODS
The PF was performed in patients with incisional hernias, both midline and lateral. The primary outcome measured was hernia recurrence. The secondary outcomes were to evaluate pain, surgical site infection, seroma, hematoma, wound dehiscence, pseudo-recurrence, Clavien-Dindo score for complications, and the patient's reported quality of life. The quality of life was assessed by oral questionnaires in the follow-up period.
RESULTS
We analyzed 63 patients (38 female, 25 male) with a mean width of hernia defect of 11 cm SD 4. Based on the European Hernia Society (EHS) classification 42 patients were W3 and 21 were W2 hernias. Fifty patients had a midline hernia, while the rest of the patients included transverse, subcostal, and rooftop incision hernias. The classical peritoneal flap procedure was done in 29 (46%) patients, while the peritoneal flap with TAR was done in 34 (54%) patients. Four patients had symptomatic seroma (6%), seven superficial surgical site infection (SSI) (11%), one deep SSI (1.5%), one skin necrosis (1.5%), and one anterior peritoneal flap necrosis (1.5%). No patient required postoperative ventilatory support. The mean pain score on day one was 3/10. There was no recurrence in the mean follow-up of 17 months (range 5 to 49 months). Overall, 58 of 63 (92%) patients reported being satisfied with their surgery.
CONCLUSION
In our multicentre study, we found the PF technique with or without TAR for midline and non-midline ventral hernia leads to satisfactory outcomes in terms of low recurrence, low rate of complications, and a good quality of life in the medium to long term. It appears to be a useful technique in the surgeon's armamentarium to repair W2 and W3 hernias needing expansion of abdominal domain.
PubMed: 38568349
DOI: 10.1007/s10029-024-02993-2 -
Paediatric Drugs May 2024Necrotizing enterocolitis (NEC) is a life-threatening disease predominantly affecting premature and very low birth weight infants resulting in inflammation and necrosis... (Review)
Review
Necrotizing enterocolitis (NEC) is a life-threatening disease predominantly affecting premature and very low birth weight infants resulting in inflammation and necrosis of the small bowel and colon and potentially leading to sepsis, peritonitis, perforation, and death. Numerous research efforts have been made to better understand, treat, and prevent NEC. This review explores a variety of factors involved in the pathogenesis of NEC (prematurity, low birth weight, lack of human breast milk exposure, alterations to the microbiota, maternal and environmental factors, and intestinal ischemia) and reports treatment modalities surrounding NEC, including pain medications and common antibiotic combinations, the rationale for these combinations, and recent antibiotic stewardship approaches surrounding NEC treatment. This review also highlights the effect of early antibiotic exposure, infections, proton pump inhibitors (PPIs), and H receptor antagonists on the microbiota and how these risk factors can increase the chances of NEC. Finally, modern prevention strategies including the use of human breast milk and standardized feeding regimens are discussed, as well as promising new preventative and treatment options for NEC including probiotics and stem cell therapy.
Topics: Humans; Enterocolitis, Necrotizing; Infant, Newborn; Milk, Human; Anti-Bacterial Agents; Probiotics; Risk Factors; Infant, Premature
PubMed: 38564081
DOI: 10.1007/s40272-024-00626-w -
Journal of Visualized Experiments : JoVE Mar 2024In patients with severe necrotizing pancreatitis, pancreatic necrosis and secondary infection of surrounding tissues can quickly spread to the whole retroperitoneal...
In patients with severe necrotizing pancreatitis, pancreatic necrosis and secondary infection of surrounding tissues can quickly spread to the whole retroperitoneal space. Treatment of pancreatic abscess complicating necrotizing pancreatitis is difficult and has a high mortality rate. The well-accepted treatment strategy is early debridement of necrotic tissues, drainage, and postoperative continuous retroperitoneal lavage. However, traditional open surgery has several disadvantages, such as severe trauma, interference with abdominal organs, a high rate of postoperative infection and adhesion, and hardness with repeated debridement. The retroperitoneal laparoscopic approach has the advantages of minimal invasion, a better drainage route, convenient repeated debridement, and avoidance of the spread of retroperitoneal infection to the abdominal cavity. In addition, retroperitoneal drainage leads to fewer drainage tube problems, including miscounting, displacement, or siphon. The debridement and drainage of pancreatic abscess tissue via the retroperitoneal laparoscopic approach plays an increasingly irreplaceable role in improving patient prognosis and saving healthcare resources and costs. The main procedures described here include laying the patient on the right side, raising the lumbar bridge and then arranging the trocar; establishing the pneumoperitoneum and cleaning the pararenal fat tissues; opening the lateral pyramidal fascia and the perirenal fascia outside the peritoneal reflections; opening the anterior renal fascia and entering the anterior pararenal space from the rear; clearing the necrotic tissue and accumulating fluid; and placing drainage tubes and performing postoperative continuous retroperitoneal lavage.
Topics: Humans; Retroperitoneal Space; Debridement; Abscess; Laparoscopy; Pancreatitis, Acute Necrotizing; Necrosis
PubMed: 38557558
DOI: 10.3791/66162 -
Inflammopharmacology Jun 2024Gout is a metabolic condition characterized by the accumulation of urate crystals in the synovial joints. These crystal depositions result in joint swelling and...
Gout is a metabolic condition characterized by the accumulation of urate crystals in the synovial joints. These crystal depositions result in joint swelling and increased concentration of serum uric acid in blood. The commercially available drugs lower serum uric acid levels and reduce inflammation, but these standard therapies have many side effects. This study aimed to investigate anti-gout and anti-inflammatory properties of curcumin nanoparticles (CNPs). For this purpose, CNPs were prepared by dissolving curcumin into dichloromethane. Then, gout was induced by injecting monosodium urate crystals (MSU) in the ankle joint and in the intra-peritoneal cavity which caused ankle swelling and increased blood uric acid levels. CNPs in different concentrations (5, 10, and 20 ppm) and allopurinol were orally administered. The MSU crystals increased the xanthine oxidase levels both in serum and the liver. Moreover, MSU crystals increased the serum levels of interleukin 1β, interleukin-6, tumor necrosis factor-alpha, liver function tests markers, renal function tests markers, and lipid profiles. However, the administration of CNPs decreased the levels of all these variables. CNPs increased the serum high-density lipoprotein and interleukin-10 levels. Moreover, CNPs also reduced ankle swelling significantly. Hence, the levels of xanthine oxidase, uric acid and ankle swelling were reduced significantly by oral administration of CNPs. Our findings indicate that CNPs through their anti-inflammatory properties significantly alleviate gouty arthritis. Thus, the study concluded that CNPs can be developed as an efficient anti-gout agent with minimal side effects.
Topics: Animals; Curcumin; Uric Acid; Arthritis, Gouty; Mice; Nanoparticles; Anti-Inflammatory Agents; Mice, Inbred BALB C; Male; Xanthine Oxidase; Gout Suppressants; Inflammation
PubMed: 38556563
DOI: 10.1007/s10787-024-01450-x