Normal Control Group Research Articles

Lingguizhugan decoction alleviates obesity in rats on a high-fat diet through the regulation of lipid metabolism and intestinal microbiota

BackgroundIndividuals with obesity often experience elevated blood lipid levels, leading to a chronic low-grade inflammatory state, exacerbating liver oxidative stress, and increasing the risk of various metabolic diseases. Recent evidence suggests that intestinal microbiota and short-chain fatty acids (SCFAs) play crucial roles in the development and progression of obesity. While the mechanisms by which Lingguizhugan decoction (LGZGD) intervenes in obesity by improving lipid metabolism, enhancing insulin sensitivity, and reducing inflammatory responses are well-documented, its potential in intestinal microbiota and SCFAs remains unclear. This study aims to explore the impact of LGZGD on high-fat diet (HFD) induced obesity in rats and its regulatory effects on intestinal microbiota and SCFAs, providing new insights for obesity prevention and treatment.MethodsFifty-one male SD rats were randomly divided into groups, with six in the normal control group (NC) receiving a ddH2O treatment and a standard diet. The remaining 45 rats were fed a high-fat diet (HFD) using D12451 feed. After 10 weeks, the rats on the HFD gained 20% more weight than the NC group, confirming the successful modeling of obesity. These rats were then randomly divided into the following groups: ddH2O high-fat diet model group (MC), 20 mg/kg/day Orlistat positive control group (Orlistat), 1.62 g/kg/day low-dose LGZGD group (LGZGL), and 3.24 g/kg/day high-dose LGZGD group (LGZGH) for 8 weeks. We evaluated changes in body weight, serum total cholesterol (TC), total triacylglycerol (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) levels. Fat and liver tissues were collected for pathological analysis. Intestinal contents were aseptically collected for 16S rRNA gene sequencing and gas chromatography–mass spectrometry (GC–MS) to assess gut microbiota and SCFA levels.ResultsLGZGD reduces body weight, TC, TG, LDL, and HDL levels, significantly reducing hepatic steatosis. Besides, it restored the richness and diversity of gut microbiota, which was reduced by HFD, altering the overall structure. Specifically, LGZGD significantly promoted the growth of Muribaculaceae and Dubosiella while inhibiting the growth of Christensenellaceae_R_7_group and UCG_005. It also restricts the production of caproic acid. Correlation analysis indicated positive correlations: Muribaculaceae with Butyric acid and Isovaleric acid; UCG_005 with TC, LDL, and HDL; and Christensenellaceae_R_7_group with TC and LDL.ConclusionLGZGD increased the abundance of beneficial gut microbiota in HFD-induced obese rats, improved gut microbiota dysbiosis, and inhibited the increase in caproic acid content. These results suggest that LGZGD can mitigate HFD-induced obesity, and its active components warrant further investigation.

Protective Effects of Isostrictiniin Against High-Fat, High-Sugar Diet-Induced Steatosis in MASLD Mice via Regulation of the AMPK/SREBP-1c/ACC Pathway

Objectives: Isostrictiniin (ITN), a natural polyphenol extracted from Nymphaea candida (snow-white waterlily), has antioxidant and hepatoprotective activities that may be beneficial in treating metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to investigate the protective effects of ITN on high-fat, high-sugar diet (HFSD)-induced steatosis in MASLD mice and its mechanisms. Methods: Kunming mice were randomly divided into normal control and HFSD groups. After being fed for 4 weeks, the HFSD group was randomly divided into model, atorvastatin calcium (ATC; 10 mg/kg), and ITN (25, 50, and 100 mg/kg) groups. After continued feeding for 4 weeks, the biochemical indexes in the mice were determined. Results: Compared with the model group, the liver index; FBG; HOMA-IR; serum AST, ALT, TG, TC, and LDL-C; and liver MDA, IL-6, TNF-α, and IL-1β levels in the ITN (25, 50, and 100 mg/kg) and ATC (10 mg/kg) groups were significantly decreased (p < 0.05), while serum HDL-C and liver SOD and GSH-Px levels were increased (p < 0.05). Pathological observation showed that ITN treatment mitigated the lipid liver deposition in the HFSD mice. Moreover, ITN could upregulate liver-tissue p-AMPK/AMPK protein expression in the HFSD-induced MASLD mice and downregulate SREBP-1c and ACC levels (p < 0.05). Conclusions: ITN can significantly improve MASLD mice, and its mechanism may be related to the regulation of the AMPK/SREBP-1c/ACC pathway.

Abstract 4119744: Evaluation of Neuropsychological development and Factors Affecting it in Children With Cyanotic and Acyanotic Congenital Cardiac Disease After Surgical Treatment

Objective: To evaluate neuropsychological development in children with cyanotic and acyanotic congenital heart diseases (CHDs) after surgical treatment and analyze the risk factors. Methods: 89 children who received follow-up in Fuwai Hospital after surgical treatment of CHDs were recruited in this study and 90 normal children were recruited as the control group. The children with CHDs were divided into cyanotic CHDs group and acyanotic CHDs group. Neuropsychological development was assessed according to Pediatric-psychological mental test scale and statistical analysis was employed. Results: The acyanotic CHDs group achieved better distribution of development quotient than cyanotic CHDs group (p < 0.05) but worse than the normal control group (p = 0.004). The proportion in cyanotic CHDs group with developmental quotient below the moderate level was higher than that of the normal control group (p < 0.001), but there was no significant difference between the cyanotic CHDs group and acyanotic CHDs group (p = 0.055). Multivariate regression analysis indicated that for cyanotic CHDs group, younger age at cardiac surgery, lower body mass, lower preoperative blood glucose level, lower BIS level, and prolonged duration of tracheal intubation after surgery were linked with lower scores in the test scale (p < 0.05); for acyanotic CHDs group, younger age at cardiac surgery, lower body mass, lower temperature during surgery and prolonged duration of tracheal intubation after surgery were linked with lower scores in the test scale(p < 0.05). Conclusion: Distinct neuropsychological impairment could be present in children with cyanotic CHDs. Younger age at cardiac surgery, body mass, preoperative blood glucose level, BIS level during surgery, temperature during surgery and duration of tracheal intubation after surgery were perioperative factors that could influence long-time neuropsychological development in children with CHDs.

Changes in soluble PD-L1 levels in patients with advanced non-small cell lung cancer

Abstract Soluble programmed death-1 ligand (sPD-L1) in the serum of non-small cell lung cancer (NSCLC) patients is a crucial factor in disease prognosis and an indicator for immunotherapy response. This study aimed to evaluate changes in sPD-L1 levels in advanced NSCLC patients. Between May 2018 and October 2022, 80 patients with advanced-stage NSCLC and 30 healthy volunteers participated in a prospective study. The findings revealed a significant rise in sPD-L1 concentration in the lung cancer group compared to the normal control group (1.08 vs. 0.42, p < 0.001). No apparent correlation was found between sPD-L1 concentration and membrane-bound programmed death-1 ligand (mPD-L1) expression. The optimal diagnostic threshold for sPD-L1 was set at 0.92 ng/mL, showing a sensitivity of 56.25% and specificity of 77.33%, with an area under the curve (AUC) of 0.743 (p = 0.001). Although increased sPD-L1 levels were prevalent in individuals with advanced age, prolonged disease duration, large tumor size, and finger clubbing, these associations did not reach statistical significance (p > 0.05). In conclusion, sPD-L1 levels significantly increased in advanced NSCLC patients compared to controls (p < 0.05), with no association observed with mPD-L1 (p = 0.304). The study suggests that sPD-L1 concentration can be a specific biomarker for guiding the diagnosis of advanced NSCLC, with a recommended cutoff value of 0.92 ng/mL, demonstrating a sensitivity of 56.25% and specificity of 77.33% (p = 0.001). Importantly, no apparent relationship was established between sPD-L1 levels and clinical or paraclinical characteristics in advanced NSCLC patients.

Biochemical Studies of Averrhoa carambola Ethanol Leaf and Fruit Extracts on Alloxan-induced Diabetic Rats

The use of herbal medicines has always been an option to treat diseases such as diabetes cancer and other ailments. This study aimed to evaluate the effect of Averrhoa carambola leaf and its fruit ethanol extracts on biochemical parameters and histopathology features. Forty five albino rats were assigned into 9 groups of 5 rats each. Except for the normal control group, others were induced to be diabetic by a single intraperitoneal injection of alloxan. Group 1 (normal control) and Group 2 (diabetic untreated) received water. Group 3 received 2.5mg/kg glibenclamide, Groups 4-9 received graded doses (250mg/kg, 500mg/kg and 750mg/kg) of leaf and fruit extracts of Averrhoa carambola. Treatment lasted 14days. At the end of the treatment, blood samples and organ (pancreas) were collected from the animals for biochemical and histopathological evaluation. Treatment of alloxan-induced diabetic rats significantly (p<0.05) reduced the glucose concentration across all treated groups. Following induction of diabetic mellitus, the serum activities of liver enzymes (Alanine amino transferase, Aspartate aminotransferase and Alkaline phosphatase), low-density lipoprotein cholesterol (LDL-C) and triglyceride were significantly (p<0.05) elevated in diabetic untreated group with corresponding reduction in serum protein, albumin and high-density lipoprotein cholesterol (HDL-C) compared to the normal control and treated groups. However, the fruit extracts exhibited a high increase in urea and creatinine levels especially at dose of 750mg/kg body weight when compared with the leaf though not significantly higher than the diabetic untreated group. From histopathology studies, the groups treated with the leaf extract of Averrhoa carambola showed greater structural improvement and an increase in pancreatic islet cells. Therefore this study showed that although ethanol extracts of Averrhoa carambola leaf and fruit have antidiabetic properties, the leaf extract possesses more antidiabetic effect.

SPP1 is a plasma biomarker associated with the dia gnosis and prediction of prognosis in sepsis

In this study, peripheral whole blood samples from 22 hospitalized patients and 10 healthy individuals were analyzed using a combination of Data Independent Acquisition (DIA) and Enzyme-Linked Immunosorbent Assay (ELISA) techniques to identify differentially expressed proteins (DEPs) in sepsis patients’ plasma. The aim was to provide accurate and detailed biomarkers, such as SPP1, for determining the pathological stages of sepsis. SPP1, known as osteopontin1 is a pleiotropic protein with a wide distribution and multifunctional effects. Its protein expression is associated with inflammatory changes, including variations in expression levels in infectious diseases, allergic diseases, and situations involving tissue damage. The registration number was ChiCTR1900021261.The full date of first registration year is 2018. In the affiliated hospital of southwest medical university, 22 sepsis patients were hospitalized from January 2019 to September 2020 and 10 normal healthy individuals were selected for DIA-based quantitative proteomics analysis. In addition to gene ontology analysis and Kyoto Encyclopedia of genes and genomes analysis, enrichment analysis of data was performed and target protein network was screened through joint protein–protein interaction and visualization techniques. The selected protein targets were then validated by Elisa kit. The software was used to analyze the differences comparing the control group to the sepsis group and the sepsis group, as well as between sepsis survivals and non-survivals, and a ROC curve was drawn to evaluate the diagnostic value and prognostic effect of the method of the corresponding target proteins. A total of 174 DEPs were screened by bioinformatics analysis. An analysis of go pathway enrichment revealed the following: These proteins were mainly involved in biological processes among them are the inflammation response, the metabolism of extracellular matrix, the secretion of cell secretions, the activation of cells, and the immune response. According to the Kegg pathway analysis, they were mainly involved in complement cascade polymerization, extracellular protease and glycosylase activation, protein synthesis process, biotin metabolism, leukocyte transmembrane migration, bacterial infection and phagosome formation. SPP1 was identified as a possible plasma biomarker and was therefore further validated using Elisa. As a result of experiments, it has been demonstrated that level in sepsis patients is significantly compared to the normal control group and the level is also higher in non-survivals of sepsis. The ROC curve can be used to see that it can diagnose sepsis more accurately and improve prognostic ability prediction. Cell experiments confirm that SPP1 is highly expressed in sepsis. There is a significant difference in the levels of SPP1 protein between the normal group and the sepsis group; it not only has good diagnostic significance for sepsis, but also provides corresponding reference value for patient prognosis; Therefore, it is more likely to become a biological marker of sepsis over time.

Integrated untargeted/targeted metabolomics identifies a putative oxylipin signature in patients with atrial fibrillation and coronary heart disease.

Atrial fibrillation (AF) and coronary heart disease (CHD) are closely related to metabolic dysregulation. However, the metabolic characteristics of AF patients with concomitant CHD remain unclear. The aims of this study were to elucidate the metabolic profiles of patients with AF and CHD to seek new therapeutic targets and related factors of AF combined with CHD. Untargeted metabolomics and targeted oxylipins profiling were performed to characterize the serum metabolome landscape of patients with AF, CHD, and AF comorbid CHD. The serum metabolic fingerprints of patients with AF comorbid CHD were significantly differentiated from normal controls (NC) and individuals with AF or CHD alone, and the differentiated metabolites dominated by a variety of lipid alterations in the phospholipid and fatty acid metabolism. Furthermore, the targeted profiles of oxylipins demonstrated that the levels of arachidonic acid derivatives including prostaglandins, leukotrienes, hydroxy-docosahexaenoic acids, hydroxy-eicostetraenoic acids and hydroxy-eicosatrienoic acids in patients with AF and CHD were significantly different from those in the NC, AF, and CHD groups. Several prostaglandins were positively associated with echocardiographic indicators of myocardial remodeling. This study updates metabolic insights of AF and CHD and provides potential therapeutic targets for preventing or treating AF comorbid CHD.

The potential therapeutic role of Lisinopril in augmenting the striatal neuroplasticity via the striatal ACE2/Ang1-7/MAS receptor axis in 3-nitropropionic acid-induced Huntington’s disease in rats: shifting paradigms in Huntington’s disease treatment

BackgroundThe exact pathogenesis of Huntington’s disease (HD) remains unclear. However, mitochondrial dysfunction and oxidative stress are supposed to play a significant role. The objective of this study was to examine the possible neuroprotective effect of Lisinopril (Lisino) in a 3-nitropropionic acid-produced HD in rats. MethodsSixty-four rats were divided into four groups (16/group): Group (1): Normal control group, Group (2): Lisinopril control group, Group (3): 3-NP non-treated group, and Group (4): (3-NP + Lisinopril) group. Behavior assessments (open field test, rotarod test, grip strength test) were performed along with different histological and biochemical parameters.ResultsLisinopril upregulated the expression of the ACE2/Ang1-7/MAS receptor (MasR) axis of RAS, which triggered the PI3K/Akt pathway and prompted the CREB/BDNF neurogenesis signal. Furthermore, Lisinopril remarkably downregulated the inflammatory cytokines (NF-κB, TNF-α, IFN-γ and IL-6), decreased apoptotic markers (p53, BAX/Bcl2 ratio, Cyt-c and caspase-3) and upgraded the mitochondrial TFAM content and SDH activity along with restoration of the redox mechanism by recovering SOD, catalase, GSH and Nrf2.ConclusionNotably, the outcomes of this study disclosed that Lisinopril could be a future neuroprotective therapeutic candidate against HD.

Altered resting-state brain activity of the superior parietal cortex and striatum in major depressive disorder and schizophrenia

BackgroundResting-state functional magnetic resonance imaging (fMRI) studies have shown altered brain activity in major depressive disorder (MDD) and schizophrenia (SZ). Despite differing diagnoses, SZ and MDD share similar features. However, functional brain activity similarities and differences between SZ and MDD remain unclear. MethodsParticipants with MDD, SZ, and normal controls (n=36 each) underwent resting-state fMRI scans. Amplitude of low-frequency fluctuations (ALFF) was used to analyze the preprocessed rs-fMRI data. One-way ANOVAs and post hoc analyses compared ALFF values in different brain regions. Pearson correlation analysis examined associations with clinical symptoms. ResultsComparison among the three groups revealed significant differences in ALFF values within the left superior parietal cortex (L-SPC) and bilateral striatum. Through pairwise comparisons, patients with SZ but not patients with MDD were found to exhibit increased striatum ALFF values relative to NC individuals, but decreased in MDD. Meanwhile, L-SPC ALFF values were significantly increased in patients with SZ relative to both normal control individuals and patients with MDD, while no differences in these values were observed between the normal control and MDD groups. The Pearson correlation analyses showed significant positive correlations between ALFF in the striatum and PANSS positive score, but no significant correlation with other symptom severity in SZ and MDD. ConclusionThese findings support the hypothesis of alterations in brain functional activity as a fundamental component of the pathogenesis of MDD and SZ. The observed differences in functional brain activity in the superior parietal cortex and striatum between MDD and SZ provide a neuroimaging basis that can contribute to the differential diagnosis of these debilitating conditions.

Diagnostic Accuracy of Combined Measurement of Serum Homocysteine, C-Reactive Protein, and Serum Ferritin in Mild Cognitive Impairments and Alzheimer's Disease.

Evaluation of the diagnostic accuracy of combined detection of serum homocysteine (Hcy), C-reactive protein (CRP), and serum ferritin (SF) levels in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Descriptive study. Place and Duration of the Study: Clinical Laboratory Section, Affiliated Hospital of Hebei University, Baoding, Heibei, China, from May 2022 to June 2023. Data of 120 patients with memory decline were retrospectively collected. They were divided into an MCI group and an AD group. A further 50 healthy participants were used as a normal control (NC) group. Differences in the Hcy, CRP, and SF levels between the three groups were evaluated. The specificity, accuracy, and sensitivity of these three indices in the combined or single diagnosis of AD and MCI were compared. Their associations with the severity of AD and MCI were also compared. The AD group had the highest levels of Hcy, CRP, and SF (18.79 ± 4.50, 6.35 ± 2.04, and 355.69 ± 120.36), followed by MCI (16.75 ± 3.06, 4.58 ± 2.31, and 203.48 ± 12.76), and NC group (14.32 ± 2.06, 2.06 ± 0.76, and 98.46 ± 5.06), with statistically significant differences (all p <0.001). The diagnostic efficacy of AD for CRP was 98.50%, sensitivity was 96.00%, and specificity was 94.00%, which was higher than Hcy and SF. Tested together, the area under the ROC curve was 99.90%, specificity was 98.00%, and sensitivity was 98.00%. The diagnostic efficacy of SF for MCI had sensitivity of 100.00%, and specificity of 100.00%, which was higher than that of Hcy and CRP. When the three were combined for detection, the area under the curve of SF was 100.00%, sensitivity of 100.00%, and specificity of 100.00%. The levels of Hcy, CRP, and SF were positively correlated with the severity of AD (p <0.01), while negatively correlated with the mini-mental state examination (MMSE) score (p <0.01). The combined detection of Hcy, CRP, and SF improved the diagnostic accuracy of comorbid AD and MCI. Homocysteine, C-reactive protein, Cognitive impairment, Serum ferritin, Alzheimer's disease.

Diagnostic Accuracy of Combined Measurement of Serum Homocysteine, C-Reactive Protein, and Serum Ferritin in Mild Cognitive Impairments and Alzheimer's Disease.

Evaluation of the diagnostic accuracy of combined detection of serum homocysteine (Hcy), C-reactive protein (CRP), and serum ferritin (SF) levels in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Descriptive study. Place and Duration of the Study: Clinical Laboratory Section, Affiliated Hospital of Hebei University, Baoding, Heibei, China, from May 2022 to June 2023. Data of 120 patients with memory decline were retrospectively collected. They were divided into an MCI group and an AD group. A further 50 healthy participants were used as a normal control (NC) group. Differences in the Hcy, CRP, and SF levels between the three groups were evaluated. The specificity, accuracy, and sensitivity of these three indices in the combined or single diagnosis of AD and MCI were compared. Their associations with the severity of AD and MCI were also compared. The AD group had the highest levels of Hcy, CRP, and SF (18.79 ± 4.50, 6.35 ± 2.04, and 355.69 ± 120.36), followed by MCI (16.75 ± 3.06, 4.58 ± 2.31, and 203.48 ± 12.76), and NC group (14.32 ± 2.06, 2.06 ± 0.76, and 98.46 ± 5.06), with statistically significant differences (all p <0.001). The diagnostic efficacy of AD for CRP was 98.50%, sensitivity was 96.00%, and specificity was 94.00%, which was higher than Hcy and SF. Tested together, the area under the ROC curve was 99.90%, specificity was 98.00%, and sensitivity was 98.00%. The diagnostic efficacy of SF for MCI had sensitivity of 100.00%, and specificity of 100.00%, which was higher than that of Hcy and CRP. When the three were combined for detection, the area under the curve of SF was 100.00%, sensitivity of 100.00%, and specificity of 100.00%. The levels of Hcy, CRP, and SF were positively correlated with the severity of AD (p <0.01), while negatively correlated with the mini-mental state examination (MMSE) score (p <0.01). The combined detection of Hcy, CRP, and SF improved the diagnostic accuracy of comorbid AD and MCI. Homocysteine, C-reactive protein, Cognitive impairment, Serum ferritin, Alzheimer's disease.

Study on the impact of refractive anisometropia on strabismus, stereopsis, and amblyopia in children.

To preliminarily explore the correlation between different types and degrees of refractive errors and strabismus, amblyopia, and stereopsis. A retrospective collection was conducted on a total of 145 patients with anisometropia who visited our hospital for strabismus and pediatric ophthalmology from January 2023 to August 2023.Based on the nature of anisometropia in both eyes, it was divided into 4 groups: Farsighted anisometropia (36 cases); myopic anisometropia (38 cases); astigmatic anisometropia (35 cases); mixed anisometropia (36 cases), and 30 children with normal vision were collected. Both groups of subjects underwent routine slit lamp and fundus examinations to exclude other organic eye diseases. The test indexes were: visual acuity, diopter, strabismus, far-stereoscopic vision, near-stereoscopic Titmus, and random static zero-order stereoscopic vision. The results of this study showed that compared with the normal control group, the incidence of strabismus was higher in the anisometropia group. When the refractive error was ≥1.00D, the far stereopsis and random dot static 0-order stereopsis in the anisometropia group decreased more significantly, and the difference between the groups was statistically significant (P < .05). Far-sighted and mixed astigmatism were more prone to amblyopia than myopia and regular astigmatism (P < .05). However, there was no statistical difference in near stereopsis Titmus between the anisometropia group and the control group (P > .05). Children with anisometropia are more likely to have strabismus, stereopsis and amblyopia than normal children.

Water-avoidance stress aggravates prostatic inflammation in a murine model of chronic prostatitis.

To date, few studies have considered the influence of psychological factors on chronic prostatitis (PRO) models. Here, we aimed to refine a murine PRO model combining chemically induced prostatitis with psychological stress. A total of 40 mice were randomly divided into four groups: normal control (NC) group, PRO group, water avoidance stress (WAS) group, and PRO + WAS group. Ten mice were assigned to each group: five for cystometrograms (CMGs) and five for von Frey testing and histological analysis. PRO was induced through a prostatic injection of 10% paraformaldehyde. The WAS mice were placed on the middle platform for 1 h per day for 10 consecutive days. The results of the von Frey test demonstrated that both WAS and PRO induced bladder hyperalgesia in mice, and the WAS + PRO group showed significant pelvic pain symptoms either. The CMG results suggested that the PRO group, the WAS group, and the PRO + WAS group all exhibited bladder overactivity, presented as a shortened micturition interval and decreased threshold pressure evoking bladder contraction. The symptoms of the PRO group and the PRO + WAS group were more severe than those of the WAS group. The tissue staining results indicated that WAS itself caused only mild prostatic inflammation but could significantly aggravate chemical-induced prostatic inflammation, as well as the total number of mast cells and proportion of activated mast cells. Our refined murine PRO model could manifest persistent bladder overactivity, pelvic hyperalgesia and prostatic inflammation. WAS could induce mild prostatic inflammation and aggravate primary prostatic inflammation.

Coexistence of aerobic vaginitis caused by Enterococcus faecalis and human papilloma virus (HPV) infection as a risk factor for the development of cervical intraepithelial lesions

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim&amp;lt;/strong&amp;gt; To determine the prevalence of aerobic vaginitis (AV) caused by &amp;lt;em&amp;gt;Enterococcus faecalis (E. faecalis)&amp;lt;/em&amp;gt; in human papilloma virus (HPV)-positive women with pathological Pap test and to determine the most prevalent HPV type associated with &amp;lt;em&amp;gt;E. faecalis&amp;lt;/em&amp;gt; infection.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods&amp;lt;/strong&amp;gt; This prospective study was conducted at the Gynaecology Centre &amp;quot;Dr. Mahira Jahić&amp;quot; Tuzla and Primary Health Care Centre Te&amp;amp;scaron;anj (Bosnia and Herzegovina) in the period between February 2023 and March 2024. The research included 200 women aged 25 to 50 years. The examined group consisted of 100 women with a pathological (examined group) and 100 with a normal (control group) Pap test result.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results&amp;lt;/strong&amp;gt; Pathological Pap smears were found in 60 (out of 100; 60 %) women in the examined group: cervical intraepithelial neoplasia (CIN) 1 and CIN 2 &amp;amp;nbsp;in two women, respectively, CIN 3 in seven, atypical squamous cells of undetermined significance (ASCUS) in 29 and atypical squamous cells-high-grade cannot be excluded (ASC-H) in two women. Overall (both groups) prevalence of &amp;lt;em&amp;gt;E. faecalis&amp;lt;/em&amp;gt; was 25.5% (51women); in 45 (22.5%) women &amp;lt;em&amp;gt;E. faecalis&amp;lt;/em&amp;gt; was the only bacterial isolate, of which 42 (21%) in the examined group and three (1.5%) in the control group. High-risk HPV types were found in 62 (out of &amp;amp;nbsp;100; 62%) women with the pathological Pap smear test. The association of &amp;lt;em&amp;gt;E. faecalis&amp;lt;/em&amp;gt; and high-risk HPV positive women was found in 35 (35%) cases (moderately positive correlation; r=0.198).&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion&amp;lt;/strong&amp;gt; E. faecalis is very common in HPV 16 and 18 positive women and may represent a risk factor in the development of cervical intraepithelial lesions.&amp;lt;/p&amp;gt;

Zhuangyao Jianshen Wan ameliorates senile osteoporosis in SAMP6 mice through Modulation of the GCN5L1-mediated PI3K/Akt/wnt signaling pathway

BackgroundSenile osteoporosis (SOP) is a systemic bone disease characterized by increased susceptibility to fractures. However, there is currently no effective treatment for SOP. The Zhuangyao Jianshen Wan (ZYJSW) pill is traditionally believed to possess kidney-nourishing and bone-strengthening effects, demonstrating efficacy in treating fractures. Despite this, its effectiveness and mechanism in SOP remain unclear. This study aims to investigate the therapeutic potential of ZYJSW in treating SOP in senescence accelerated mouse prone 6 (SAMP6, P6) mice, and elucidate the underlying mechanisms. MethodsFour-month-old SAMP6 mice were categorized into six groups: the model group (SAMP6), low, medium, and high-dose ZYJSW treatment groups, calcitriol treatment (positive control 1) group, and metformin treatment (positive control 2) group. Gastric administration was carried out for 15 weeks, and a normal control group comprising four-month-old Senescence-Accelerated Mouse Resistant 1 (SAMR1) mice. Changes in body weight, liver and kidney function, bone protective effects, and muscle quality were evaluated using various assays, including H&E staining, Goldner staining, bone tissue morphology analysis, Micro-CT imaging, and biomechanical testing. Qualitative analysis and quality control of ZYJSW were performed via LC-MS/MS analysis. To explore mechanisms, network pharmacology and proteomics were employed, and the identified proteins were validated by Western blotting. ResultsOral administration of ZYJSW to P6 mice exerted preventive efficacy against osteopenia, impaired bone microstructure, and poor bone and muscle quality. ZYJSW attenuated the imbalance in bone metabolism by promoting bone formation, as evidenced by the upregulation of key factors such as Runt-related transcription factor 2 (RUNX2), Bone Morphogenetic Protein (BMP2), Osteoprotegerin (OPG) and Osteocalcin (OCN), while simultaneously inhibiting bone resorption through the downregulation of TNF receptor associated factor 6 (TRAF6), Tartrate resistant acid phosphatase (TRAP), Receptor activator for nuclear factor-κB ligand (RANKL) and Cathepsin K (CTSK). Additionally, ZYJSW enhanced muscle structure and function by counteracting the elevation of Ubiquitin (Ub), Muscle RING-finger protein-1 (Murf-1), F-Box Protein 32 (FBOX32), and Myogenin (Myog). Network pharmacology predictions, proteomics analysis corroborated by published literature demonstrated the role of ZYJSW involving in safeguarding mitochondrial biogenesis. This was achieved by suppressing GCN5L1 expression, contributing to the heightened expression of TFAM, PGC-1α, and nuclear respiratory factor-1 (NRF-1) proteins. ZYJSW also positively modulated Wnt signaling pathways responsible for bone formation, due to regulating expressions of key components like β-catenin, GSK-3β, and LRP5. In addition, ZYJSW causes the downregulation of the PI3K/Akt pathway by inhibiting the phosphorylation of both PI3K and Akt. ConclusionsThe study highlights the significance of ZYJSW in preserving the health of both bone and muscle in P6 mice, potentially through the regulation of the GCN5L1-mediated PI3K/Akt/Wnt signaling pathway. The translational potential of this articleOur research provides evidence and a mechanistic rationale for ZYJSW as a candidate for SOP treatment, offering insights for further exploration and strategy development.

In Silico Analysis of novel Phytocompounds targetting Dipeptidyl peptidase 4 Enzyme: A New Link between Prediabetes and its cardio-metabolic complications

BackgroundDPP-4 inhibitors, are widely used clinically for treatment of Diabetes. Increase in circulating DPP4 levels have been well demonstrated in patients with Type 2 Diabetes mellitus. The present study assessed the contribution of DPP-4 axis to the pathophysiology of Prediabetes and its cardiometabolic complications. In addition, in silico analysis of phytocompounds that target DPP 4 enzyme was undertaken to identify novel Phytocompounds with therapeutic potential in Prediabetes. MethodologyA novel experimental model of Prediabetes coexisting with hypertension and dyslipidemia was developed in experimental rats to elucidate the pathophysiological role of DPP-4 in Prediabetes and its resultant cardio-metabolic sequale. In the Prediabetic rats, DPP-4 levels, lipid profile, blood pressure readings, fasting blood sugar values, insulin resistance, beta cell function were measured and compared to Normal Control group. In addition, the DPP-4 Inhibitory activity of Phytocompounds (Arjunetin, Guggulsterone) was studied by molecular docking studies including Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), DPP 4 binding affinity and Protein-ligand simulation between the DPP4 and the Phytocompounds was performed. Results were compared to Vildagliptin, the synthetic DPP-4 inhibitor and metformin (Glucophage), the standard antidiabetic drug used in clinical settings. ResultsA statistically significant increase (p < 0.001) in DPP-4 levels along with a decline in bea cell function with increase in Insulin resistance was observed in Prediabetic rats. A positive correlation (p < 0.001) between serum DPP-4 with HbA1c, lipids, and systolic blood pressure was found. The novel model of Prediabetes co-existing with hypertension and dyslipidemia was successfully developed and validated. The silico active site interaction data from simulation studies demonstrated that Arjunetin and Guggulsterone shows effective and stable binding with DPP-4. Arjunetin maintains its contact with Glu205, Glu206, and Asn710 and by interacting with Val207 and His740, it effectively occupies the flanking residues of the active site area. Based on their protein-ligand contact report, Vildagliptin maintains its connection through Tyr547 and during simulation, Guggulsterone interacts with Ser630. ConclusionThe current study offers experimental evidence of DPP-4′s causal role in the development of cardio-metabolic consequences (dyslipidemia and hypertension) of Prediabetes. Arjunetin and Guggulsterone are two Phytocompounds whose potential as promising DPP-4 inhibitors has been further documented using in silico molecular docking studies.

A modified deep learning method for Alzheimer’s disease detection based on the facial submicroscopic features in mice

Alzheimer’s disease (AD) is a chronic disease among people aged 65 and older. As the aging population continues to grow at a rapid pace, AD has emerged as a pressing public health issue globally. Early detection of the disease is important, because increasing evidence has illustrated that early diagnosis holds the key to effective treatment of AD. In this work, we developed and refined a multi-layer cyclic Residual convolutional neural network model, specifically tailored to identify AD-related submicroscopic characteristics in the facial images of mice. Our experiments involved classifying the mice into two distinct groups: a normal control group and an AD group. Compared with the other deep learning models, the proposed model achieved a better detection performance in the dataset of the mouse experiment. The accuracy, sensitivity, specificity and precision for AD identification with our proposed model were as high as 99.78%, 100%, 99.65% and 99.44%, respectively. Moreover, the heat maps of AD correlation in the facial images of the mice were acquired with the class activation mapping algorithm. It was proven that the facial images contained AD-related submicroscopic features. Consequently, through our mouse experiments, we validated the feasibility and accuracy of utilizing a facial image-based deep learning model for AD identification. Therefore, the present study suggests the potential of using facial images for AD detection in humans through deep learning-based methods.

External damp environment aggravates diarrhea in spleen deficiency and dampness syndrome in mice: involvement of small intestinal contents microbiota, energy metabolism, gastrointestinal and fluid functions

ObjectivesRecent studies have increasingly demonstrated that a multiplatform water environment combined with lard gavage is an effective method for establishing a mouse model of diarrhea. However, the interactions between intestinal microorganisms and diarrhea, as well as the relationships among energy metabolism, fluid balance, and gastrointestinal function in this model, remain poorly understood.MethodsBuilding on previous research, this study aimed to optimiz and replicate a multiplatform water environment combined with a lard gavage model. Male Kunming mice, free of specific pathogens, were randomly divided into four groups: a normal control group (ZC), a standing group (ZL), a standing combined with lard group (ZLZ), and a standing combined with internal and external wet conditions group (ZLZS). The mice in the ZL, ZLZ, and ZLZS groups were subjected to 4 hours of daily standing in a custom-designed multiplatform water environment. Starting on day 8, mice in the ZLZ and ZLZS groups were gavaged with lard (0.4 mL per session, twice daily) for 7 consecutive days, while those in the ZLZS group were additionally exposed to a wet litter environment (50 g/100 mL). The ZC and ZL groups received equal volumes of sterile water via gavage. The microbiota in the small intestine, as well as serum levels of cAMP, cGMP, VIP, Gas, and D-xylose, were analyzed.ResultsCompared with the ZLZ group, the ZLZS group showed significantly lower serum levels of cAMP/cGMP (p&amp;lt;0.01) and Gas (p&amp;lt;0.01). D-xylose levels were lower in the ZL, ZLZ, and ZLZS groups compared to the ZC group, while VIP levels were significantly higher in the ZL and ZLZS groups (p&amp;lt;0.01). Moverover, Corynebacterium, Empedobacter, and Pseudochrobactrum were identified as characteristic bacterial genera in the ZLZS group. The mechanism by which the small intestinal microbiota induces diarrhea was linked to the biosynthesis of secondary bile acids.ConclusionA multiplatform water environment combined with lard gavage can effectively induce diarrhea, and the addition of an external wet environment exacerbates this condition by affecting small intestinal contents microbiota and other functions.

Polyphenol-rich Ocimum gratissimum leaf extract attenuates angiotensin-converting enzyme activity and impaired endothelial vascular function in diabetic rats

Endothelial vascular dysfunctions are prevalent among diabetic patients, significantly impacting their quality of life and prognosis. This study examined the effects of polyphenol-rich extracts from Ocimum gratissimum leaves on oxidative stress markers, serum lipid profiles, and angiotensin-converting enzyme activity in diabetic cardiac tissue. Forty Wistar rats (150–220 g) were divided into five groups: normal control, diabetic control, low-dose Ocimum gratissimum (122.46 mg/kg), medium-dose Ocimum gratissimum (244.98 mg/kg), and a positive control (standard diabetic drug). All rats except the normal control group were made diabetic via an intraperitoneal injection of 50 mg/kg streptozotocin, followed by 28 days of extract administration. Diabetes induction led to a significant (p&lt;0.05) disruptions in lipid profiles, oxidative stress markers, and ACE activity. Treatment with Ocimum gratissimum extracts at both doses significantly (p&lt;0.05) decreased triglyceride, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol levels while increasing high-density lipoprotein cholesterol. Lipid peroxidation marker, malondialdehyde, was significantly (p&lt;0.05) decreased, and antioxidant enzyme activities significantly (p&lt;0.005) improved. ACE activity was significantly (p&lt;0.05) reduced, approaching control levels. These results suggest that the polyphenol-rich extract of Ocimum gratissimum exerts antioxidant and cardio-protective effects, improving vascular functions in diabetic rats by improving lipid profiles, reducing oxidative stress, and suppressing ACE activity.

Experimental study on the treatment of diabetic cardiomyopathy in rats by using ultrasound-targeted microbubble destruction combined with coenzyme Q10 loaded long-circulating nanoliposomes

Objective: To investigate the therapeutic effects and mechanisms of Ultrasound-targeted microbubble destruction (UTMD) technology combined with CoQ10 loaded PEGylated nanoliposomes (CoQ10-PEG-lips) on diabetic cardiomyopathy (DCM) in rats. Methods: CoQ10-PEG-lips were prepared using the thin-film dispersion method combined with ultrasonic hydration, followed by quality assessment. Sixty healthy and clean male SD rats were selected, and 50 were randomly chosen using a random number table to establish a type 1 diabetes mellitus (DM) model via a single intraperitoneal injection of streptozotocin. The remaining 10 rats were assigned as the normal control group. A total of 47 rats successfully developed the DM model, and 40 were selected using the random number table method. Based on different intervention methods, these rats were then randomly divided into DM model group, CoQ10 solution group, CoQ10-PEG-Lips group, and CoQ10-PEG-Lips+UTMD group (n=10 per group). Normal control group and DM model group rats were injected with 1 ml of normal saline through caudal vein. CoQ10 solution group and CoQ10-PEG-Lips group were injected with 1 ml of CoQ10 solution or CoQ10-PEG-Lips solution containing 10 mg/kg of CoQ10 through caudal vein, respectively. Rats in the CoQ10-PEG-Lips+UTMD group were injected with 1 ml of CoQ10-PEG-Lips solution containing 10 mg/kg of CoQ10+100 mg of freeze-dried ultrasound microbubble powder through caudal vein and were given UTMD treatment at the same time, with the intervention given twice a week. After 12 weeks of intervention, cardiac function indexes [left ventricular end-systolic diameter (LVEDs), left ventricular end-diastolic diameter (LVEDd), and left ventricular ejection fraction (LVEF)]of each group were measured by ultrasonic cardiac function detection in vivo. Simultaneously, ex-vivo histopathological examination was conducted to assess myocardial cell morphology, cross-sectional area, collagen volume fraction (CVF), and apoptosis index (AI) in each group. Additionally, molecular biology techniques were employed to measure oxidative stress-related indicators and the expression of apoptosis-related pathway proteins. Results: The prepared CoQ10-PEG-lips had a well-rounded morphology, good dispersibility, and a high encapsulation efficiency of 87.45%±3.23%. After 12 weeks of intervention, the myocardial cell morphology in the CoQ10-PEG-Lips+UTMD group was intact, with orderly arrangement, closely resembling that of the normal control group. There were no statistically significant differences between the two groups in terms of LVEDs [(1.53±0.07) mm vs (1.42±0.04) mm], LVEDd [(2.93±0.15) mm vs (2.81±0.05) mm], or LVEF (80.76%±3.42% vs 84.60%±2.10%) (all P>0.05). Similarly, there were no significant differences between the two groups in myocardial cell cross-sectional area, CVF, or AI (all P>0.05). The CoQ10-PEG-Lips+UTMD group showed statistically significant differences in the above-mentioned indicators compared to the DM group, CoQ10 solution group, and CoQ10-PEG-Lips group (all P<0.05). In the CoQ10-PEG-Lips+UTMD group, the levels of myocardial superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) were significantly higher compared to the DM model group, CoQ10 solution group, and CoQ10-PEG-Lips group (all P<0.05), while malondialdehyde levels and the expression of Bcl-2-associated X protein (Bax) and caspase-3 were lower (all P<0.05). Conclusions: Using PEG-lips to encapsulate the poorly soluble drug CoQ10 in combination with UTMD technology enables targeted delivery of the drug to the myocardium, which can help reduce myocardial cell damage, fibrosis, and apoptosis caused by diabetes mellitus (DM) by inhibiting oxidative stress damage and the Bcl-2/Bax/caspase-3 apoptosis signaling pathway, ultimately improving cardiac function in DCM rats.