Pathological Symptoms Research Articles

The alleviative effect of C-phycocyanin peptides against TNBS-induced inflammatory bowel disease in zebrafish via the MAPK/Nrf2 signaling pathways

IntroductionUlcerative colitis (UC) is an incurable and highly complex chronic inflammatory bowel disease (IBD) affecting millions of people worldwide. C-phycocyanin (C-PC) has been reported to possess outstanding anti-inflammatory activities and can effectively inhibit various inflammation-related diseases. Whether C-PC-derived bioactive peptides can inhibit intestinal inflammation is worth research and consideration. MethodsThe inhibition activities of three anti-neuroinflammatory peptides were evaluated using 2-4-6-trinitrobenzen sulfonic acid (TNBS)-induced zebrafish colitis model. Subsequently, the abilities of peptides to promote gastrointestinal motility were also examined. The changes in the intestinal pathological symptoms and ultrastructure of intestinal, reactive oxygen species (ROS) levels, and antioxidant enzymes were then determined after co-treatment with peptides and TNBS. Transcriptome analysis was used to investigate the underlying ameliorating TNBS-induced colitis effects molecular mechanisms of better activity peptide. Furthermore, quantitative reverse-transcription polymerase chain reaction and molecular docking techniques verified the mRNA sequencing results. ResultsThree peptides, MHLWAAK, MAQAAEYYR and MDYYFEER, which significantly inhibit macrophage migration, were synthesized. The results showed that these peptides could effectively alleviate the inflammatory responses in the TNBS-induced zebrafish model of colitis. In addition, co-treatment with TNBS and C-PC peptides could decrease ROS production and increase antioxidant enzyme activities in zebrafish larvae. Moreover, MHLWAAK had the most significantly therapeutic effects on colitis in zebrafish. The transcriptome analysis suggests that the effect of MHLWAAK on TNBS-induced colitis may be associated with the modulation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and mitogen-activated protein kinase (MAPK) signaling pathway associated genes. In addition, molecular docking was conducted to study the prospective interaction between peptides and the key proteins that streamline the Nrf2 and MAPK signaling pathways. IL-6, JNK3, TNF-α, KEAP1-NRF2 complex and MAPK may be the core targets of MHLWAAK in treating colitis. ConclusionThe results suggested that the three C-PC-derived peptides could ameliorate TNBS-induced colitis in zebrafish, and these peptides might be a promising therapeutic candidate for UC treatment.

Brewers’ spent grain as fish feed ingredient: Evaluation of bio-safety and analysis of its impact on gut bacteria of Cirrhinus reba by 16S Metagenomic sequencing

A comprehensive eight week feeding trial was conducted to investigate the potential of brewers' spent grain (BSG) as a sustainable fish feed ingredient. The study assessed both the biosafety of BSG and its impact on the gut microbiome of Cirrhinus reba, utilizing advanced 16S metagenomic sequencing techniques to analyze the composition and diversity of gut bacteria. A total of 90 healthy C. reba juveniles (average weight: 12 ± 1 g) were divided into two dietary groups [for control (C), for BSG meal (tB)] in triplicates. Feed prepared with conventional ingredients was used to feed the control group (C). The group tB was fed with BSG meal. After the feeding trial, the fish in tB group showed significantly higher (p < 0.05) growth parameters as compared to the control group. The results of bio-safety assessment indicated the absence of any pathological symptoms in the BSG meal fed carps. The fish in tB group didn't show any histopathological abnormality. Fish fed the Brewers' Spent Grain exhibited significantly elevated serum biochemical parameters, including alanine transaminase (ALT) and aspartate transaminase (AST), compared to the control group (p < 0.05). 16S Metagenomic sequencing of the fish gut microbiota provides insights into how BSG inclusion affects microbial diversity and composition within the digestive tract of C. reba. The analysis revealed the existence of 240 and 250 diverse bacterial genera in the gastrointestinal tract (GIT) of C. reba in dietary groups C and tB respectively. Importantly, the study found the gut of fish in tB group to be dominated by different beneficial genus including Bacillus, Lactobacillus, Bifidobacterium, Paenibacillus, and Lysinibacillus. Feeding C. reba with BSG meal significantly increased the alpha diversity of the gastrointestinal microbiota, as evidenced by elevated Chao 1 estimator and Shannon index values compared to the control diet (p < 0.05). This study provides comprehensive evidence for the bio-safety of BSG as a sustainable feed ingredient in aquaculture, demonstrating its potential to support healthy fish growth and development. Moreover, the prebiotic potential of BSG in fish has also been highlighted.

Microenvironment-responsive nanosystems for ischemic stroke therapy.

Ischemic stroke, a common neurological disorder caused by impaired blood supply to the brain, presents a therapeutic challenge. Conventional treatments like thrombolysis and neuroprotection drugs lack ideal drug delivery systems, limiting their effectiveness. Selectively delivering therapies to the ischemic cerebral tissue holds great potential for preventing and/or treating ischemia-related pathological symptoms. The unique pathological microenvironment of the brain after ischemic stroke, characterized by hypoxia, acidity, and inflammation, offers new possibilities for targeted drug delivery. Pathological microenvironment-responsive nanosystems, extensively investigated in tumors with hypoxia-responsive systems as an example, could also respond to the ischemic cerebral microenvironment and achieve brain-targeted drug delivery and release. These emerging nanosystems are gaining traction for ischemic stroke treatment. In this review, we expound on the cerebral pathological microenvironment and clinical treatment strategies of ischemic stroke, highlight various stimulus-responsive materials employed in constructing ischemic stroke microenvironment-responsive nano delivery systems, and discuss the application of these microenvironment-responsive nanosystems in microenvironment regulation for ischemic stroke treatment.

Astragaloside IV Mediates the PI3K/Akt/mTOR Pathway to Alleviate Injury and Modulate the Composition of Intestinal Flora in ApoE-/- Atherosclerosis Model Rats.

Atherosclerosis (AS) is a chronic inflammatory vascular disease with a complex pathogenesis. Astragaloside IV (AST IV), the primary active component of Astragalus, possesses anti-inflammatory, antioxidant, and immunomodulatory properties. This research aims to investigate the outcome of AST IV on AS and its potential molecular mechanism. A high-fat diet (21% fat, 50% carbohydrate, 20% protein, 0.15% cholesterol, and 34% sucrose) was utilized to feed Apolipoprotein E deficient (ApoE-/-) SD rats for 8 weeks, followed by continuous intragastric administration of AST IV for 8 weeks. Biochemical detection was conducted for serum lipid levels and changes in vasoactive substances. After Masson staining, aortic root oil red O staining, and Hematoxylin Eosin (HE) staining, the efficacy of AST IV was verified using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The mRNA expression levels of inflammatory factors and endothelial dysfunction-related biomarkers in rat aortic root tissues were appraised. The changes in the composition of intestinal flora in rats after AST IV treatment were appraised using Image J (Multi-point Tool). Western blot was used to evaluate phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway-related protein levels in rat aortic root tissues. AST IV administration alleviated the pathological symptoms of AS rats. AST IV administration reduced serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), endothelin-1 (ET-1) and angiotensin (Ang)-II (Ang-II) levels, and augmented serum high-density lipoprotein cholesterol (HDL-C) and nitric oxide (NO) levels. At the same time, AST IV administration inhibited the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, vascular cell adhesion molecule-1 (VCAM-1), matrix metalloproteinase-2 (MMP-2), macrophage inflammatory protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) in the aortic root tissue of AS rats. In addition, the intestinal flora changed significantly after AST IV administration. The number of Bifidobacterium, Lactobacillus, and Bacteroides augmented significantly, and Enterobacter, Enterococcus, Fusobacterium, and Clostridium significantly decreased. Mechanistically, AST IV administration inhibited the phosphorylation of PI3K, Akt, and mTOR in AS rats. When combined with Dactolisib (BEZ235) (a PI3K/Akt/mTOR pathway inhibitor), AST IV could further inhibit phosphorylation and reduce inflammation. AST IV has a potential anti-AS effect, which can improve the pathological changes of the aorta in ApoE-/- rats fed with a high-fat diet, reduce the level of inflammatory factors, and modulate the composition of intestinal flora via the PI3K/Akt/mTOR pathway.

Involvement of gut microbiota recovery and autophagy induction in Youhua Kuijie formula's protection against experimental ulcerative colitis.

Ulcerative colitis (UC) is characterized by overactive inflammatory response, impaired intestinal mucosal barrier and disrupted gut microbiota. Youhua Kuijie formula is a classic empirical prescription based on the pathogenesis of UC. The present study was designed to verify the protective effect of Youhua Kuijie formula on DSS-induced UC in mice and uncover the related mechanism. Youhua Kuijie formula were orally administrated to UC mice induced by DSS dissolved in drinking water for ten days. The protective effect of Youhua Kuijie formula was evidenced by reduced pathological symptoms accompanied by palliative inflammatory response and relatively intact intestinal barrier. The data from 16S rRNA gene sequencing and GC-MS untargeted metabolomics indicated that the supplement of Youhua Kuijie formula restructured gut microbiota community structure, and thereby modulated the metabolic profiles in UC mice. The analysis of pathway enrichment analysis suggested the major alterations in metabolic pathway were related to protein digestion and absorption. Besides, the results of the following experiments suggested that Youhua Kuijie formula treatment increased adenosine monophosphate-activated protein kinase (AMPK) activation, decreased mechanistic target of rapamycin (mTOR) phosphorylation, and thereby reversing autophagy deficiency in the intestinal tract of UC mice. Collectively, our results demonstrated that the regulation of AMPK/mTOR was involved in Youhua Kuijie formula administration mediated protective effect on UC.

Implantable bioelectrodes: challenges, strategies, and future directions.

Implantable bioelectrodes for regulating and monitoring biological behaviors have become indispensable medical devices in modern healthcare, alleviating pathological symptoms such as epilepsy and arrhythmia, and assisting in reversing conditions such as deafness and blindness. In recent years, developments in the fields of materials science and biomedical engineering have contributed to advances in research on implantable bioelectrodes. However, the foreign body reaction (FBR) is still a major constraint for the long-term application of electrodes. In this paper, four types of commonly used implantable bioelectrodes are reviewed, concentrating on their background, development, and a series of complications caused by FBR after long-term implantation. Strategies for resisting FBRs are then devised in terms of physics, chemistry, and nanotechnology. We analyze the major trends in the future development of implantable bioelectrodes and outline some promising research to optimize the long-term operational stability of electrodes. Although current implantable bioelectrodes have been able to achieve good biocompatibility, low impedance, and low mechanical mismatch and trauma, these devices still face the challenge of FBR. Resistance to FBR is still the key for the long-term effectiveness of bioelectrodes, and a better understanding of the mechanisms of FBR, as well as miniaturization, long-term passivation, and coupling with gene therapy may be the way forward for the next generation of implantable bioelectrodes.

Investigation of the therapeutic effects and mechanisms of Houpo Mahuang Decoction on a mouse model of chronic obstructive pulmonary disease.

With a growing global population affected by Chronic Obstructive Pulmonary Disease (COPD), the traditional Chinese herbal formula Houpo Mahuang Decoction (HPMHD) has been used for centuries to address respiratory ailments. While studies have demonstrated the therapeutic benefits of HPMHD in COPD, the effective active ingredients, potential targets, and molecular mechanisms underlying its effectiveness remained unclear. The mechanisms of action of certain HPMHD components, targets, and pathways for the treatment of COPD were predicted using a network pharmacology method. We induced a COPD mouse model using porcine pancreatic elastase and evaluated the pathological changes and healing processes through HE and Masson staining. Immunofluorescence was used to assess the levels of IL-6 and TNF-ɑ. RNA-Seq analysis was conducted to identify differentially expressed genes (DEGs) in the lungs of normal, control, and treated mice, revealing the biological pathways enriched by HPMHD in COPD treatment. Finally, the expression of DEGs was verified using Western blotting and RT-qPCR. HPMHD effectively alleviated pathological symptoms and improved COPD in mice by modulating the IL-17 signaling pathway. Treatment with HPMHD improved lung morphology and structure, reduced inflammatory cell infiltration, and inhibited IL-6 and TNF-ɑ levels. Network pharmacology and transcriptomics further revealed the mechanism, indicating that the IL-17 signaling pathway might been instrumental in the inhibitory effect of HPMHD on mouse model of COPD. Subsequent experiments, including protein blotting and RT-qPCR analysis, confirmed the activation of the IL-17 signaling pathway by HPMHD in the COPD mouse model, further supporting the initial findings. HPMHD was shown to alleviate COPD and reduce lung inflammation in mice, potentially through the activation of the IL-17 signaling pathway. This study provides a novel direction for the development of COPD drugs.

XinJiaCongRongTuSiZiWan protects triptolide-induced rats from oxidative stress injury via mitophagy mediated PINK1/Parkin signaling pathway.

XinJiaCongRongTuSiZiWan (XJCRTSZW) is a traditional Chinese medicine compound for invigorating the kidney, nourishing blood, and promoting blood circulation. This study aimed to explore the effect of XJCRTSZW on triptolide (TP)-induced oxidative stress injury. Adult female Sprague-Dawley rats and human ovarian granulosa cell lines were treated with TP and XJCRTSZW. Hematoxylin and eosin staining, enzyme-linked immunosorbent assay, flow cytometry, CCK-8, JC-1 staining, transmission electron microscopy, reverse transcription-quantitative polymerase chain reaction, and Western blotting were performed in this study. XJCRTSZW treatment observably ameliorated the TP-induced pathological symptoms. Furthermore, XJCRTSZW treatment observably enhanced the TP-induced reduction of estradiol, anti-Mullerian hormone, progesterone, superoxide dismutase, ATP content, mitochondrial membrane potential, p62, and Hsp60mRNA, and protein levels in vivo and in vitro (p < 0.05). However,TP-induced elevation of follicle stimulating hormone and luteinizing hormone concentrations, malondialdehyde levels, reactive oxygen species levels, apoptosis rate, mitophagy, and the mRNA and protein expressions of LC3-II/LC3-I, PTEN-induced kinase 1 (PINK1), and Parkin were decreased (p < 0.05). In addition, XJCRTSZW treatment markedly increased cell viability in vitro (p < 0.05). XJCRTSZW protects TP-induced rats from oxidative stress injury via the mitophagy-mediated PINK1/Parkin pathway.

Zhi Zhu Ma Ren pill relieves constipation in mice through endoplasmic reticulum stress-mediated apoptosis.

This study explores the detailed effects and mechanisms of Zhi Zhu Ma Ren Pill (ZZMRP) on constipation. Mouse constipation was induced by using loperamide (Lop). The effects and mechanisms of ZZMRP on constipation were addressed by various methods including charcoal meals, hematoxylin and eosin (H&E) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL), transmission electron microscopy, and western blot experiments. Lop-treated mice exhibited delayed transit and reduced ink progradation rates after charcoal meal administration. H&E staining confirmed severe pathologic symptoms in these mice. Additionally, a decline in interstitial Cajal cells (ICCs) was observed in Lop-treated mice, accompanied by reduced concentrations of 5-hydroxytryptamine (5-HT), acetylcholinesterase (AchE), substance P (SP), and vasoactive intestinal peptide (VIP), coupled with an elevated concentration of nitric oxide synthase (NOS). However, ZZMRP treatment markedly ameliorated these changes. In addition, ZZMRP introduction significantly reversed the Lop-induced enhancement in apoptosis rate, endoplasmic reticulum (ER) stress, and levels of proapoptotic proteins and ER stress proteins, and the decrease in the expression of antiapoptotic proteins. These effects were further confirmed with the use of 4-phenylbutyrate (4-PBA), which also reversed the changes in apoptosis rate and protein levels. ZZMRP alleviates constipation primarily through modulating ER stress-mediated apoptosis in Lop-treated mice, suggesting its use as a therapeutic agent for constipation.

α-Mangostin suppresses ethanol-induced gastric ulceration by regulating the Nrf2/HO-1 and NF-κB/NLRP3/caspase-1 signaling pathways and gut microbiota

α-Mangostin is a natural xanthone derivative isolated from Camellia atrophy (CA), commonly known as Lichuan black tea (LBT). The present study investigated the ameliorating effect and mechanism of α-mangostin on alcoholic gastric ulcers (GU) in rats. In vivo, α-mangostin relieved pathological symptoms. Moreover, α-mangostin regulated the activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) and nuclear factor κB (NF-κB)/NLR family pyrin domain containing 3 (NLRP3)/caspase-1 pathways. Reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were significantly decreased and IL-10 were increased, the microtubule-associated protein light chain 3 (LC3)-II/LC3-I ratio was increased, p62 protein expression was decreased, and inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expression was down-regulated. The relevant mechanisms were validated using GSE-1 and RAW264.7 cells in an in vitro model. Furthermore, α-mangostin increased Ligilactobacillus and Muribaculum abundance as well as propionic acid and butyric acid contents. Therefore, α-mangostin possesses antioxidant and anti-inflammatory properties, and remodels intestinal flora dysbiosis through mechanisms that may involve regulation of the Nrf2/HO-1 pathway and NF-κB/NLRP3/caspase-1 pathway. It also increases propionic acid and butyric acid contents. This study provides novel evidence regarding the use of α-mangostin for treating GU.

An Unusual Case of Anaemic Retinopathy Secondary to Iron Deficiency Anaemia

Anaemia has varied ocular presentations, ranging from simple conjunctival pallor to retinal abnormalities. Anaemic Retinopathy (AR) is a secondary retinal pathological symptom that can range from asymptomatic to developing retinal abnormalities. The increase in the severity of anaemia will ultimately increase the risk of retinopathy. While the outcomes might be similar to hypertensive or diabetic retinopathy, further comprehensive systemic and clinical evaluation is warranted. The incidence of AR, its associations with varying degrees of anaemia severity, and other haematological variables is still debated. Visual loss due to retinal abnormalities in anaemia is a rare clinical entity, despite its long-standing existence. Hereby, the authors present a case of a patient presenting with AR. A 19-year-old woman with a history of heavy menstrual bleeding was admitted for a sudden, painless, non progressive loss of vision in her left eye. Upon examination, her fundus revealed several Roth spots affecting all four quadrants and the macula, alongside a large and small preretinal haemorrhage in the nasal region and in the macula. Blood investigations revealed a Haemoglobin (Hb) of 2.4 g/dL and other reports suggestive of iron deficiency. She was diagnosed with iron-deficiency anaemia, with retinopathy as the most remarkable feature. She was treated with blood transfusion and Iron-folic Acid (IFA) supplementation, which showed a prompt response in the resolution of haemorrhage. She was discharged on IFA supplementation with planned follow-up for Ophthalmology and Gynaecology visits along with dietary advice.

TINGKAT PENGETAHUAN LANSIA TERHADAP OSTEOARTHRITIS KNEE DI POSYANDU ANGGREK TUNJUNG SEKAR

Osteoarthritis of the knee is a degenerative joint disease characterized by pathological symptoms in the entire joint structure, cartilage damage, development of osteophytes and sclerosis at the edges of the bones, stretching of the joint capsule, inflammation and weakness. the muscles around the joint. Risk factors for knee osteoarthritis are genetics, age, gender, obesity and metabolic disorders. This study aims to determine the level of knowledge of elderly people regarding knee osteoarthritis. This type of research uses outreach and poster methods as output results. Before being given counseling, 0% of the 10 respondents did not know information related to knee osteoarthritis, but after being given the counseling, 100% of the 10 respondents were able to answer all questions in the questionnaire correctly. There is a difference in respondents' knowledge before and after being given education about knee osteoarthritis.

Revascularization in Immature Permanent Teeth - A Case Series

Immature permanent teeth with developing, root apices with dental pulp infections resulting from caries or trauma represent a formidable clinical challenge. Biologically based principles of regenerative endodontic procedures in the treatment of immature, necrotic teeth have replaced the traditional ‘apexification’ procedures. The purpose of this case series was to investigate the outcome of the pulpal revascularization procedure on immature permanent teeth with or without apical periodontitis. The case series comprised 3 patients (8–11 years of age), consisting of 4 incisors and 1 premolar with incompletely formed apex with or without signs or symptoms of periapical pathology. Induction of blood clot was the technique selected for root closure if the tooth was asymptomatic following the placement of intracanal antibiotic paste for 3 weeks. Apexification was initiated if the tooth remains symptomatic. Out of the five teeth revascularisation was successful, and continued root-end closure was obtained in four teeth. One tooth remained symptomatic and apexification was initiated. One patient failed to follow up for the study. Revascularisation by induction of apical bleeding is a potential source of stem cells for the continued root maturation and it creates a blood clot that would act as a biologic scaffold for the recruited stem cells.

Fluor Albus Characteristics Associated with Sexually Transmitted Infection (STI) in Makassar Pregnant Women

Sexually Transmitted Infection (STI) is a common condition with increased prevalence among pregnant women and can negatively affect the fetus. According to WHO, a total of 374 million new cases of STI are projected to occur in 2020, including gonorrhea (82 million), syphilis (7.1 million), and trichomoniasis (156 million). Therefore, this study aimed to determine the relationship between the characteristics of vaginal discharge (fluor albus) in pregnant women and STI. The descriptive method was used with a cross-sectional design, and the procedures were conducted in May 2023. The sample population comprised all pregnant women with ANC in Makassar during the study period. Vaginal swabs were obtained from 127 pregnant women who were willing to participate and had vaginal discharge. The results showed that 53 participants reported having physiological flour albus, while 74 had pathological symptoms. Itching and odor were reported to be the most common clinical signs associated with patients' abnormal vaginal discharge, followed by itching, pain, and odor. Furthermore, a significantly high prevalence of the condition was observed among pregnant women aged 20-30 years. Based on the results, the predominant symptom of fluor albus was itching and odor when combined with microorganisms that caused STI. Several pregnant women with clinical complaints also had microorganisms apart from those associated with STI. These results indicated the pressing need to develop additional testing in pregnant women with fluor albus, particularly those with concomitant symptoms.&#x0D; &#x0D;

Mối liên quan giữa mức độ sao chép gen KIAA1199 với một số đặc điểm lâm sàng, giải phẫu bệnh của người bệnh ung thư đại trực tràng tại Bệnh viện đa khoa Đức Giang năm 2022-2023

Background: Determine the level of KIAA1199 gene copy in FFPE tissue samples of colorectal cancer (CR) patients and evaluate of the relationship between KIAA1199 gene copy level and some clinical and pathological symptoms of CRC patients at Duc Giang General Hospital in year 2022-2023. Methods: A cross-sectional descriptive study on 40 FFPE samples and 40 corresponding medical records of CRC patients diagnosted and treated at Duc Giang General Hospital in year 2022-2023. Result: 26/40 FFPE tissue samples (65.0%) were processed to meet the requirements for RNA extraction quality to evaluate the KIAA1199 gene copy level. Furthermore, 20/26 samples (76.9%) had a higher level of KIAA1199 gene copy in tumor tissue than in normal tissue. There was a statistically significant association between increased KIAA1199 gene copy levels and level of tumor differentiations and types in CR patients (p&lt;0.05); among them, CR patients with neoplasms have increased 11.3 times the KIAA1199 gen copy level higher than CR patients with other types of tumors (p&lt;0.05). However, it was not possible to evaluate the statistically significant relationship between the KIAA1199 gene copy level and some histopathological characteristics such as tumor location, tumor number, histopathological type, level of serosal invasion, lymph node metastasis, and stages classified according to TNM (p&gt;0.05). Conclusion: In this study, the KIAA1199 gene copy levels in tumor tissue increased more strongly than in normal tissue and a statistically significant relationship between the increased KIAA1199 gene copy levels and the tumor differentiations and types in CR patients (p&lt;0.05).

Frailty and Increased Levels of Symptom Burden Can Predict the Presence of Each Other in HNSCC Patients.

Frailty is an important risk factor for adverse events (AEs), especially in elderly patients. Therefore, assessing frailty before therapy is recommended. In head and neck squamous cell carcinoma (HNSCC) patients, frailty is prognostic for severe postoperative complications and declining quality of life (QoL) after HNSCC treatment. Thus, assessment of frailty may help to identify individuals at risk for AE caused by oncologic therapy. We investigated the relationship between frailty and symptom burden to better understand their interaction and impact on HNSCC patients. In this prospectively designed cross-sectional study, the presence of frailty and symptom burden was assessed by using the Geriatric 8 (G8) and Minimal Documentation System (MIDOS2) questionnaires. A total of 59 consecutively accrued patients with a first diagnosis of HNSCC before therapy were evaluated. Patients were considered frail at a total G8 score ≤ 14. The MIDOS2 symptom burden score was considered pathological with a total score ≥ 4 or any severe symptom (=3). Statistical correlations were analyzed using Spearman and Pearson correlation. Receiver operator characteristic (ROC) curves were used to analyze the potential of predicting frailty and MIDOS2. p-values < 0.05 were considered significant. A total of 41 patients (69.5%) were considered frail, and 27 patients (45.8%) had increased symptom burden. "Tiredness" was the most common (overall rate 57.8%) and "Pain" was the most often stated "severe" symptom (5 patients, 8.5%). G8 and MIDOS2 correlated significantly (ρ = -0.487, p < 0.001; r = -0.423, p < 0.001). Frailty can be predicted by MIDOS2 symptom score (AUC = 0.808, 95% CI 0.698-0.917, p < 0.001). Vice versa, the G8 score can predict pathological symptom burden according to MIDOS2 (AUC = 0.750, 95% CI 0.622-0.878, p < 0.001). Conclusions: The strong link between frailty and increased symptom burden assessed by G8 or MIDOS2 indicates a coherence of both risk factors in HNSCC patients. Considering at least one of both scores might improve the identification of individuals at risk and achieve higher QoL and reduced complication rates by decision making for appropriate therapy regimens.

Momordica charantia Polysaccharide intervention ameliorates the symptoms of dextran sulfate sodium (DSS)-induced colitis by modulating gut microbiota and inhibiting inflammation

Momordica Charantia Polysaccharide (MCP), the main active ingredient of M. charantia, exhibits multiple pharmacological properties. However, its effects and mechanisms against ulcerative colitis (UC) remain unclear. In this study, we employed a dextran sulfate sodium (DSS)-induced experimental colitis model to investigate the therapeutic potential of MCP. Our results revealed that prophylactic MCP dramatically attenuated the pathological symptoms associated with colitis in mice, including body weight loss, reduction in colon length, and tissue damage. Moreover, we found prophylactic MCP reduced DSS-induced intestinal permeability and enhanced intestinal barrier integrity. Notably, we observe that prophylactic MCP restored the diversity and richness of the gut microbiota, thereby ameliorating gut microbiota dysbiosis in DSS-induced mice models. Furthermore, fecal microbiota transplantation (FMT) experiments demonstrated that the microbiota derived from MCP-dosed mice remarkably alleviated colitis symptoms. Collectively, our study provided valuable insights into the potential of MCP as a promising prebiotic agent for maintaining intestinal health, and demonstrated that MCP ameliorated colitis in a gut microbiota-dependent manner.

Pathogenic Factors and Recent Study on the Rapid Detection of Shiga Toxin-Producing Escherichia coli (STEC).

This comprehensive review delves into the pathogenicity and detection of Shiga Toxin-Producing Escherichia coli (STEC), shedding light on its various genetic and clinical manifestations. STEC originating from E. coli acquires pathogenicity through mobility and genetic elements. The pathogenicity of STEC is explored in terms of clinical progression, complications, and key toxins such as Shiga toxin (Stx). Stx1 and Stx2 are two distinct Stx types exhibiting different toxicities, with Stx2 often associated with severe diseases. This review also delves into Subtilase cytotoxin, an additional cytotoxin produced by some STEC strains. Pathogenic mechanisms of STEC, such as attaching and effacing intestinal lesions, are discussed, with a focus on roles of genetic factors. Plasmids in STEC can confer unique pathogenicity. Hybridization with other pathogenic E. coli can create more lethal pathogens. This review covers a range of detection methods, ranging from DNA amplification to antigen detection techniques, emphasizing the need for innovative approaches to improve the sensitivity and speed of STEC diagnosis. In conclusion, understanding diverse aspects of STEC pathogenicity and exploring enhanced diagnostic methods are critical to addressing this foodborne pathogen effectively. Pathology of Shiga toxin toxicity. STEC-derived Shiga toxin consists of one A subunit and five B subunits. Pathological symptoms of the disease can progress to HUS within two weeks after the onset of diarrhea. Shiga toxin intoxication is also associated with many complications, such as neurological and cardiac complications. This figure was reconstructed based on data from Bruyand et al.

Adenosine A2A receptor antagonist KW6002 protects against A53T mutant alpha-synuclein-induced brain damage and neuronal apoptosis in Parkinson's disease mice by restoring autophagic flux

BackgroundProtein misfolding and inclusion body aggregation caused by α-Syn mutations in the brain often cause neurodegeneration and cognitive impairment, among which the A53T point mutation is more common. Inhibition of adenosine A2A receptor (A2AR) can alleviate the pathological symptoms of brain dysfunction caused by A53T-α-Syn protofibrils, but the mechanism of action is still unclear. AimThis studies aimed to investigate the potential therapeutic role of the A2AR inhibitor KW6002 in a mouse model of brain synucleinopathy. MethodsA53T-α-Syn fibre precursor cell nuclear protein was injected into the bilateral prefrontal cortex of mice to establish a synucleinopathy animal model, and the A2AR inhibitor KW6002 (5 mg/kg) was injected intraperitoneally to intervene. ResultThe intracerebral injection of A53T-α-Syn protofibrils triggers the formation of inclusion bodies in the brain, leading to astrocyte activation, an increased number of apoptotic cells, and suppression of autophagic flux. The administration of KW6002 significantly reversed these phenomena. In vitro experiments revealed that A53T-α-Syn protofibrils inhibited HT-22 autophagy in mouse hippocampal neuronal cells, whereas KW6002 increased cellular autophagic flux, upregulated the expression of LAMP2A and Hsc70 proteins and inhibited the expression of SQSTM1 protein. The present study suggests that KW6002 reduces the level of α-Syn phosphorylation by inhibiting A2AR protein, at the same time, enhances the autophagic flux of neuronal cells, resulting in the degradation of A53T-α-Syn protofibrils and thus reducing the neuronal toxicity and apoptosis induced by A53T-α-Syn protofibrils. ConclusionKW6002 has a significant protective effect on neuronal injury induced by A53T-α-Syn.

Subclinical Hypothyroidism and Functional Hemodynamics of the Heart

Subclinical hyperthyroidism (SHyper), a laboratory decrease in thyroid-stimulating hormone levels with peripheral thyroid hormone levels within the reference interval, is considered a medical condition, especially its impact on cardiac hemodynamics among young women. To determine the effects of subclinical thyroid dysfunction on hemodynamics in young women. clinical observation included two groups of women: (1) the main group consisted of 30 patients with subclinical hyperthyroidism, which was examined at the Family Medicine Clinic of the West Kazakhstan Marat Ospanov Medical University (Aktobe, Kazakhstan) and (2) the control group consisted of 30 practically healthy women. The groups were comparable in age (30–42), mean age 36.2±7.0 years. Blood pressure (BP) was measured, heart rate (HR) was counted, and thyroid hormones were determined. in the examined patients, clinical symptoms of pathology were not observed; laboratory tests determined a decrease in thyroid-stimulating hormone (TSH) in the main group of patients to 2.48±0.23 mIU/L in comparison with the control group 3.65±1.3 mIU/L, which was significant (p0.05) increase in blood pressure SBP/DBP from 122.34±2.7/78.3±2.7 to 127.8±3.1/83.2±2.1 mmHg and HR from 77.7±1.9 to 82.2±2.6 in 1 minute. A significant (r2 =0.482) interaction was determined between TSH -0.236 mIU/L and HP +20.3 in 1 minute, this could be a predictor of an increase in heart rate greater than the reference value (60–80 per minute), and an increased heart rate is considered a predictor of an increase in blood pressure. Subclinical hyperthyroidism may produce a significant laboratory decrease in TSH, without significant clinical symptoms of increased blood pressure. In conclusion, current observational experience suggests that small decreases in laboratory values of thyroid-stimulating hormone may affect blood pressure and heart rate.