Pretreatment Group Research Articles

Optimization of the cholesterol gallstone model in C57BL/6 mice and evaluation of Lactobacillus intervention effects

Gallstone disease is a common and complex condition, strongly associated with abnormal cholesterol metabolism, changes in bile composition, and impaired gallbladder motility. Recent studies have suggested that the gut microbiota, particularly probiotics like lactic acid bacteria, may play a significant role in the prevention and treatment of cholesterol gallstones. This study aims to optimize the cholesterol gallstone model in C57BL/6 mice and evaluate the effects of Lactobacillus intervention on gallstone formation induced by a high-fat diet. In this study, 8-week-old male C57BL/6 mice were randomly divided into four groups: a high-fat diet + saline group (HF-S), a high-fat diet + probiotic group (HF-P), a normal diet + saline group (ND-S), and a normal diet + probiotic group (ND-P), to assess the effect of probiotics on gallstone formation. The results showed significant differences among the four groups in body weight gain, liver weight, gallstone formation, and histopathology. Based on these preliminary findings, we added two more experimental groups: a 2-week probiotic pretreatment + high-fat diet group (Pre2w-HF) and a 4-week probiotic pretreatment + high-fat diet group (Pre4w-HF), to further investigate the dose-dependence and efficacy of probiotic pretreatment. The results indicated that probiotic intervention significantly reduced the incidence and severity of gallstones induced by a high-fat diet, with the pretreatment groups showing more pronounced effects. Histological analysis also revealed that probiotic intervention reduced inflammation and pathological changes in the liver and gallbladder. This study suggests that probiotics have potential therapeutic value in the prevention and treatment of cholesterol gallstones. Future research should explore the effects of different strains and doses, as well as the underlying mechanisms involved.

Reducing diltiazem-related hypotension in atrial fibrillation: Role of pretreatment intravenous calcium.

This study evaluated the efficacy of intravenous (IV) calcium pretreatment for preventing diltiazem-induced hypotension and assessed its safety in adult patients with atrial fibrillation (AF)/atrial flutter (AFL) with rapid ventricular response (RVR). This randomized, double-blind, placebo-controlled trial included 217 adults with AF/AFL and a ventricular rate>120 beats per minute, who were randomized into three groups: those who received an IV NaCl 0.9% placebo pretreatment prior to IV diltiazem (PD; 73 patients) and those who received 90mg (C90D; 71 patients) and 180mg (C180D; 73 patients) IV calcium chloride pretreatment before IV diltiazem. We compared participants' systolic blood pressure (SBP) and heart rate (HR) at baseline and at 5, 10, and 15min post-treatment, as well as the incidence of adverse events (e.g., hypotension, urticaria, nausea) among the groups. The PD and C90D pretreatment groups had significantly lower HR measurements at 10 and 15min compared to the C180D group. In addition, at 5min, the mean SBP in the PD group was significantly lower compared to the C90D and C180D groups. At 10min, the mean SBP was significantly higher in the C180D group than in the other groups. Furthermore, at 15min, the mean SBP was significantly higher in both the C90D and C180D groups than in the PD group. There were no significant differences between the calcium pretreatment and placebo groups in terms of the need for additional diltiazem doses or the incidence of adverse events. IV calcium pretreatment effectively prevents diltiazem-induced hypotension in patients with AF/AFL with RVR without compromising the efficacy of diltiazem in achieving and maintaining ventricular rate control. National Library of Medicine Clinical Trial Registry; No.: NCT06494007; URL: https://clinicaltrials.gov/study/NCT06494007.

Therapeutic Effects of Lavender Oil on Streptozotocin-Induced Diabetes Mellitus and Experimental Thrombosis

Diabetes mellitus is a metabolic disorder associated with oxidative stress, inflammation, and coagulation disturbances, which contribute to microvascular and macrovascular complications. We evaluated the therapeutic effects of lavender oil (Lavandula angustifolia) in a streptozotocin (STZ)-induced rat model of type 1 diabetes mellitus (T1DM) with experimentally induced thrombosis. Sixty male Wistar rats were divided into control, thrombosis, diabetes, thrombosis–diabetes, and lavender oil pretreatment groups (100 and 200 mg/kg body weight [bw]). Lavender oil exhibited dose-dependent benefits, with the 200 mg/kg bw dose leading to significant reductions in proinflammatory cytokines (e.g., tumor necrosis factor α (TNF-α); regulated upon activation, normal T cell expressed and secreted (RANTES); and monocyte chemoattractant protein-1 (MCP-1)) and oxidative stress, along with improved glycemic control, the partial restoration of C-peptide levels, and the attenuation of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9) activity (p < 0.0001). Histopathological and coagulation analyses confirmed its organ-protective and antithrombotic effects, including reduced tissue damage, vascular inflammation, and thrombus formation, and prolonged bleeding and clotting times. Our findings suggest that lavender oil exhibits dose-dependent antioxidant, anti-inflammatory, hypoglycemic, and organ-protective effects, indicating its potential as a complementary therapy for managing inflammation in T1DM with or without thrombosis.

Molecular mechanism underlying cardioprotective effect of dehydroepiandrosterone on endoplasmic reticulum stress induced apoptosis in human vascular smooth muscle cells and human umbilical vein endothelial cells

IntroductionThis study aimed to investigate the underlying mechanisms involved in the cardioprotective effects of dehydroepiandrosterone (DHEA) on endoplasmic reticulum stress (ERS) -mediated apoptosis in human vascular smooth muscle cells (HVSMCs) and human umbilical vein endothelial cells (HUVECs).Material and methodsVarious concentrations of Dithiothreitol (DTT) were used to induce ERS-mediated apoptosis. DHEA was utilized to inhibit the apoptotic effects of DTT, while estrogen receptor (ER) antagonists ICI 182,780 and G15, the androgen receptor (AR) antagonist flutamide and the aromatase inhibitor letrozole were used to identify the receptors activated during DHEA treatment in HVSMCs and HUVECs. Flow cytometry assessed the apoptotic rate, and Western blotting analysis evaluated the expression levels of ERS-related proteins GRP78 and PERK, and the apoptotic protein marker CHOP. Furthermore, the primary receptor signaling pathways were identified using signaling pathway blockers: LY294002 (PI3K blocker), SP600125 (JNK blocker), and U0126 (ERK1/2 blocker).ResultsIn the DTT pretreatment group (0.8 mmol/L, for 8 h), the expressions of GRP78 and CHOP were significantly up regulated, indicating that an optimal ERS model was successfully established. Additionally, 10-4 mmol/L DHEA significantly inhibited the DTT-induced upregulation of GRP78 and CHOP. The results also demonstrated that the apoptotic rate in the DTT group was increased, while DHEA significantly reduced this rate. The addition of ER antagonists ICI 182,780 and G15 to HVSMCs reversed the effects of DHEA; however, the aromatase inhibitor letrozole and the AR antagonist flutamide did not reverse this effect. Notably, the use of the JNK inhibitor SP600125, the PI3K inhibitor LY294002, and the ERK1/2 inhibitor U0126 antagonized the protective effects of DHEA, with SP600125 showing the most significant impact on both HVSMCs and HUVECs.ConclusionOur study has identified a novel mechanism underlying the cardioprotective effects of DHEA. Specifically, DHEA may mitigate ERS-induced cell apoptosis by activating estrogen receptors ERα, ERβ, and GPER via the activated JNK pathway.

Effect of probiotics combined with immune checkpoint suppressors and chemotherapeutic agents on digestive system function, intestinal immunity and prognosis in patients with metastatic colorectal carcinoma: a quasi-experimental study

ObjectiveAn exploration of the influence of probiotics combined with immune checkpoint suppressors and chemotherapeutic agents on digestive system function, intestinal immunity and prognosis in patients with metastatic colorectal carcinoma.MethodsThis was a quasi-experimental study. During March 2019 to March 2020, 96 patients with metastatic colorectal carcinoma were arbitrarily classified into control group (n = 48) and intervention group (n = 48). The control group received only immune checkpoint inhibitors or chemotherapy, while the intervention group received immune checkpoint inhibitors or chemotherapy, plus probiotic therapy. Survival and complication rates after 6 months, 12 months and 2 years of treatment were calculated. Intestinal barrier function, immune function and quality of life were analyzed before and after treatment.ResultsNinety-six patients were recorded at the follow-up demonstrating superior survival in the intervention group after 6 months, 12 months and 2 years of therapy. D-lactate and diamine oxidase (DAO) levels were elevated in the intervention group after treatment, with smaller elevations (P < 0.05). The levels of Bifidobacterium and Lactobacillus were remarkably higher in the intervention group after treatment compared to the control group prior to and following therapy (P < 0.05). The amount of Enterococcus and Escherichia coli in the intervention group after treatment was obviously lower compared to the pre-treatment and control groups (P < 0.05). CD3+, CD4+, and CD4+/CD8+ levels were found to be higher in the intervention group (P < 0.05), while CD8+ levels were reduced in the intervention group (P < 0.05). All dimensions of the QLQC-30 scale were higher in the intervention group (P < 0.05). The incidence of complications such as nausea and vomiting, loss of appetite, bloating and diarrhea was considerably reduced in the intervention group (P < 0.05).ConclusionImmune checkpoint suppressors combined with chemotherapeutic agents or probiotic regimens can obviously enhance the prognosis of patients with metastatic colorectal carcinoma. This combination therapeutic strategy can balance the imbalanced intestinal flora, improve intestinal function, and lessen the incidence of adverse events, so it is worthy of clinical application and can lessen the incidence of adverse reactions.

Central administration of p234, kisspeptin antagonist, but not kisspeptin-10, reduces the power of epileptiform activity and slow EEG waves in male rats

ABSTRACT Introduction We aimed to investigate the effects of central kisspeptin-10 and p234 administration on basal brain activity and epilepsy-like conditions induced by 4-aminopyridine (4-AP), as well as their roles in the electrocorticogram (ECoG) power spectrum and EEG waves. Methods Thirty-five male Wistar rats were divided into five groups: sham,4-AP (2.5 mg/kg i.p.), kisspeptin-10 post-treatment (200 pmoli.c.v.), p234 post-treatment (1 nmol i.c.v.), and p234 pre-treatment (1 nmol i.c.v.). We performed 70 minutes of recordings (10 min baseline) for all groups under ketamine/xylazine (90/10 mg/kg) anesthesia. In the post-treatment groups, kisspeptin-10 or p234 injections were administered 20 minutes after epilepsy induction. In the pre-treatment group, p234 was injected after baseline recordings. Following a 20-minute pre-treatment period, 4-AP was administered. Results 4-AP alone induced epileptiform activity in all animals, reaching apeak after 30 minutes. Neither kisspeptin-10 nor p234 post-treatment affected 4-AP-induced epileptiform activity (p > 0.05). However, p234 pre-treatment reduced epileptiform activity (p < 0.05). Additionally, kisspeptin-10 did not alter the spectral analysis of the EEG bands or the power of the ECoG (p > 0.05). In contrast, p234 reduced the power of the ECoG and the slow bands (delta and theta) (p < 0.05). Conclusion We conclude that p234 pre-treatment has an inhibitory effect on neuronal excitability and epileptiform activity in the neocortex.

Laminated Layer Extract from Echinococcus Granulosus cyst Attenuates Ocular Damages and Inflammatory Responses in an Experimental Autoimmune Uveitis Model.

Since extract of the laminated layer (LL) from E. granulosus showed immuno-modulatory effects in vitro and in vivo, we sought to determine its effect on the onset, development, and evolution of experimental auto-immune uveitis (EAU). The latter is a model of some human diseases with ocular inflammation that can cause blindness. E. granulosus LL extract was either injected before EAU induction for the pretreated group or later for treated group. Ocular exploration was made by retinal histological and immunohistological (CD86, CD4, CD8) analysis. Myeloperoxidase (MPO), Superoxide dismutase (SOD), Catalase enzymatic activities (CAT), and Malondialdehyde (MDA), Nitric oxide (NO), Urea, and TNF-α levels were measured in plasma. LL injection attenuated retinal histological damage and reduced cells infiltration. Also, LL decreased systemic inflammatory and oxidative markers as well as TNF-α production and increased antioxidant parameters. Interestingly, we observed a protective effect of E. granulosus LL extract during EAU. LL appears to ameliorate retinal damage by down-regulating inflammatory responses. Our results support LL immunomodulatory effects during autoimmune diseases and offer a promising prospect for helminthic therapy during autoimmune uveitis.

Preventive impact of probiotic supplements on heart injury and inflammatory indices in a rat model of myocardial infarction: histopathological and gene expression evaluation.

Although there is a bulk of evidence on the favorable effect of probiotics on the cardiac system, their role in the management of myocardial infarction is not clear. Three viable probiotic bacterial strains, namely Lactobacillus reuteri, Bifidobacterium longum, and Bifidobacterium lactis, were gavaged to the rats daily for 28 days prior to the induction of myocardial injury. Myocardial injury was induced by the use of isoproterenol (ISO) in the probiotics, control and sham groups. The heart tissues were catheterized to evaluate the histopathological parameters and measure the expression of genes related to inflammation. Treatment with ISO caused subendocardial necrosis and rupture of cardiac myofibrils. Pretreatment with probiotics reduced the size of myocardial infarction caused by ISO. Also, in the probiotic group, a relative decrease in the amount of tissue fibrosis and rupture of cardiomyocytes fibers was seen. Pretreatment with probiotics partially ameliorated myocardial necrosis, edema and leukocyte infiltration. Also, a remarkable decrease was detected in the expression of tissue proinflammatory genes in the pretreated group with probiotics. Thus, viable probiotic supplementation may ameliorate or prevent cardiac injury. Additional preclinical and clinical studies are required to clarify the impact of probiotics in the prevention and management of cardiovascular disease.

Oral administration of Limosilactobacillus reuteri VHProbi® M07 alleviates ovalbumin-induced allergic asthma in mice.

Asthma is characterized by chronic airway inflammation, persistent cough, wheezing, and dyspnea. This study aimed to evaluate the efficacy of Limosilactobacillus reuteri VHProbi® M07 (M07) administration in alleviate the asthma severity in a mice model. In vitro studies confirmed that M07 can survive and proliferate within the gastrointestinal tract. BALB/c mice were administered M07 both before and after ovalbumin (OVA) challenge. Serum levels of OVA-specific immunoglobulin (Ig) E and IgG1, inflammatory cells and cytokines in bronchoalveolar lavage fluid were assessed, along with histopathological examination of lung tissue. Compared to the placebo (PLA) group, mice treated with M07 exhibited significantly lower levels of OVA-specific IgE and IgG1 (P < 0.01). The counts of eosinophils and neutrophils were also significantly reduced in both the pretreated (PRE) group and post-treated (POS) group compared with the PLA group (P < 0.01). Histological analysis of lung tissues verified the protective effects of M07 against inflammation, demonstrating reduced infiltration of inflammatory cells. Additionally, mice in the PRE and POS groups showed significantly increased levels of IL-10 (P < 0.01), and significantly decreased levels of IL-5, IL-13, MCP-1, eotaxin, and tumor necrosis factor-α (P < 0.01). Oral administration of M07 mitigated key features of inflammatory responses in the OVA-induced mice asthma model. These findings suggest that M07 holds therapeutic potential for the treatment of allergic asthma.

In vivo, in vitro, and in silico approaches in the detailed study of di-butyl phthalate (DBP), a plasticizer-induced lung fibrosis via Nrf-2/Keap-1/HO-1 pathway and its regulation.

The alveolar epithelium is a crucial barrier against external threats, yet it becomes a key player in initiating pulmonary fibrosis when compromised. Despite its importance, the intricate relationship between, DBP exposure and alveolar epithelial cell injury ensuing pro-fibrotic effects remains poorly understood. Phthalates, ubiquitous in nature, pose a significant risk to lung health upon inhalation, acting as immune triggers that cause airway inflammation and epithelial damage. We aimed to investigate the impact of intranasal administration ofDi-butyl Phthalate (DBP) inhalation, and its probable effects on normal and asthmatic lungs. DBP was administered via intranasal route in normal and OVA-induced asthmatic mice. DBP exposure enhanced oxidative stress and inflammatory parameters, leading to exacerbated asthmatic response and oxidative lung damage. Enhanced accumulation of immune cells, bronchial thickening, and collagen deposition was noted in histopathological investigations of DBP-exposed lung sections. Curcumin, a plant-derived molecule, significantly mitigated DBP-exposed asthma exacerbations by suppressing NF-κB expression and enhancing NRF2 levels via the Nrf-2/Keap-1/HO-1 signaling pathway. FACS analysis revealed increased CD11b+ cells (32%) in asthmatic mice which were reduced in the curcumin pre-treatment group (10.5%). Enhanced epithelial to mesenchymal transition (EMT) was noted in mice lungs and A549 cells where E-cadherin expression was reduced as compared to Vimentin, and α-SMA. Apart from aggravated airway inflammation, DBP exposure damages healthy lungs also. MMP-9/TIMP-1 ratios and collagen-1 levels were restored which were enhanced after DBP exposure. Moreover, antioxidant enzyme levels such as NQO-1, HO-1, and Catalase were significantly enhanced (p<0.01) and comparable to dexamethasone, a conventional corticosteroid. Notably, both dexamethasone and curcumin treatments effectively regulated the stimulation and accumulation of Nrf-2 in the nucleus, promoting antioxidant production and offering potential therapeutic benefits in mitigating pulmonary fibrosis. OVA and DBP alone caused DNA damage in the lung cells where increasedpercentage of damaged DNA movement in thetail, tail length, tail moment, and olive tail moment indicated severe damage in theDBP and OVA combined exposure strategies. Dexamethasone and Curcumin treatments reduced theextent of the DNA damage indicating anti-inflammatory and ant-oxidative potentials. Moreover, in silico studies are supportive of therapeutic potential of Curcumin and Dexamethasone in DBP-induced lung inflammation and fibrosis.

Balloon angioplasty versus Shockwave intravascular lithotripsy in calcified coronary arteries: the BASIL study.

Severe coronary calcification is a predictor for procedural failure during percutaneous coronary intervention (PCI). Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify coronary calcification to optimize stent results. The efficacy of IVL compared to conventional balloon angioplasty (BA) prior to drug-eluting stent (DES) implantation is largely unknown. This study aimed to compare pretreatment with IVL vs BA for severely calcified coronary lesions prior to DES implantation. A total of 60 patients with severely calcified coronary disease undergoing PCI were randomly assigned (1:1 ratio) to conventional BA or IVL pretreatment groups. The primary efficacy endpoint was procedural success (successful stent implantation without bailout calcium modification devices, no major angiographic complications, and residual stenosis less than 20%). The primary safety endpoint was freedom from in-hospital major adverse cardiovascular events (MACE) including death, periprocedural myocardial infarction, stroke, and target vessel revascularization/target lesion failure. Procedural success was achieved in 15 (55.6%) patients in the BA group and 24 (72.7%) patients in the IVL group (P = .165). Requirement for bailout calcium modification was higher in the BA group (22.2% vs 0.0%; P = .004). The primary safety endpoint was achieved in 26 (96.3%) patients in the BA group and 30 (90.9%) patients in the IVL group (P = .405). In PCI of severely calcified coronary disease, no significant differences in procedural success or in-hospital MACE were identified when comparing IVL to conventional BA pretreatment. There was a higher need for additional dedicated calcium modification observed with conventional BA.

Peripheral blood complement factors C2 and C3 as biomarkers of clinical efficacy in patients with first-episode schizophrenia after aripiprazole treatment

ObjectiveThe objective of this study was to identify serum complement factor-based biomarkers indicative of clinical efficacy in patients with first-episode schizophrenia (SCZ) following treatment with aripiprazole.MethodsThe retrospective study cohort comprised 40 patients diagnosed with first-episode SCZ (SCZ group) and 40 healthy individuals (control group). Quantitative analyses were conducted on five complement factors, namely complement component 1 (C1), C2, C3, C4, and the 50% hemolytic complement (CH50). Baseline serum complement factor levels were compared between the SCZ and control groups. Patients diagnosed with SCZ underwent a 4-week treatment regimen with aripiprazole. The severity of psychiatric symptoms in these patients was assessed using the Positive and Negative Symptom Scale (PANSS) and the Brief Psychiatric Rating Scale-18 Item Version (BPRS). Comparative analyses were conducted on PANSS and BPRS scores, as well as serum complement factor levels, both prior to (pre-treatment group) and following aripiprazole administration (post-treatment group). Pearson’s correlation test was employed to evaluate the relationships between changes in serum complement factor levels and the reduction rates of PANSS/BPRS scores.ResultsAt baseline, patients with SCZ exhibited significantly elevated levels of C1, C2, C3, C4, and CH50 compared to the control group (P < 0.05). Moreover, following treatment, there was a significant reduction in the PANSS total score, positive symptom score, negative symptom score, and BPRS score in the post-treatment group compared to the pre-treatment group (P < 0.05). Furthermore, patients in the post-treatment group exhibited a significant reduction in serum levels of C2, C3, and C4, alongside a significant increase in the serum level of CH50 compared to those in the pre-treatment group (P < 0.05). Additionally, the baseline serum C2 levels and the variations in serum C2 levels pre- and post-treatment exhibited a negative correlation with the reduction rate of PANSS/BPRS scores (P < 0.05). Similarly, both the baseline serum C3 levels and the changes in serum C3 levels pre- and post-treatment were negatively correlated with the reduction rate of PANSS/BPRS scores (P < 0.05).ConclusionBaseline serum levels of C2 and C3, as well as their variations pre- and post-treatment, may serve as biomarkers for predicting clinical efficacy in patients with first-episode SCZ undergoing treatment with aripiprazole.

Influence of surface pretreatment using cold-active atmospheric pressure plasma on bond strength of CAD-CAM-fabricated hybrid ceramic crowns: an in-vitro study.

This study assesses the impact of Cold Atmospheric Pressure Plasma (CAP) pretreatment on the bond strength of two-piece hybrid ceramic abutment crowns in implant dentistry. The objective is to ascertain whether CAP can be employed as an alternative or complementary technique to conventional methods. 80 titanium bases and 80 VITA ENAMIC® polymer-infiltrated ceramic network (PICN) crowns were divided into 8 groups (n = 10) based on different surface pretreatments of the crowns before cementation: no treatment (A), hydrofluoric acid (HF) (B), HF and silane (C), silane (D), CAP (AP), HF and CAP (BP), HF, CAP, and silane (CP), and CAP and silane (DP). Bond strength (BS) was measured after thermocycling (5000 cycles at 5°C/55°C), and statistical analysis was performed using three-way ANOVA. The highest bond strength (BS) was recorded in the conventionally pretreated group C. Both HF and silane alone had significant effects (p < 0.0001), but CAP alone did not (p = 0.9377). Significant interactions were found between silane and CAP (p = 0.0222), and HF and CAP (p = 0.0046). The combined effects exceeded individual effects. Although group C showed the highest BS, no significant interaction was found between HF and silane (p = 0.6270). Three-factor interactions were significant (p < 0.0001). In the setting used, CAP could not replace conventional pretreatment. The highest BS of a group without HF was achieved by combining silane with CAP. However, BS of this pretreatment was approximately 24% lower than that of the conventional pretreatment.

Randomized Clinical Trial of Intraocular Pressure-Lowering Medications on Preventing Spikes in Intraocular Pressure Following Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are a primary management option for retinal diseases. Acute elevation of intraocular pressure (IOP) is a complication associated with these injections that should be considered. This study investigated and compared the prophylactic effects of fixed combination anti-glaucoma medication on IOP spikes following intravitreal anti-VEGF injections. This randomized double-blind clinical trial included one eye of each participant indicated for treatment with intravitreal injection of anti-VEGF agents (bevacizumab, aflibercept, and ranibizumab) and randomly allocated to one of the three prophylactic anti-glaucoma medications, with each drug further divided into one- and two-drop regimens before intravitreal injection. Participants with allergies or contraindications to medications were excluded from the pretreatment groups and were invited to participate in the control group. The study involved 308 participants: 89 in the dorzolamide/timolol group, 86 in the brimonidine/timolol group, 101 in the brinzolamide/brimonidine group, and 32 in the control group. Baseline characteristics and IOP were comparable across all groups. In the prophylactic premedication groups, mean IOP at 30min were within 21mmHg and returned to their baseline at 1h. Mean IOP measurements between baseline and 30min in the brimonidine/timolol two-drop regimen were not significantly different: 13.72 ± 4.63 vs 15.11 ± 4.39mmHg, p = 0.096. In the control group, IOP significantly increased from baseline at 30min and 1h post-injection: 14.31 ± 4.10, 22.15 ± 8.64, and 18.36 ± 7.52mmHg, respectively, p < 0.001. Topical fixed combination anti-glaucoma medication used as a prophylactic treatment before intravitreal anti-VEGF injections significantly prevented IOP spikes post-injection, with a comparable effect among three medications. Prophylactic treatment of IOP spikes should be considered as standard care to prevent further damage in patients with compromised retinal vascular and optic nerve perfusion. TCTR20241005001, retrospectively registered.

Effect of Gonadotropin-Releasing Hormone Agonist Pre-Treatment on Outcomes of Fresh and Frozen Embryo Transfers in Women With Adenomyosis: A Retrospective Cohort Study With Literature Review.

To investigate the effect of gonadotropin-releasing hormone agonist (GnRHa) pre-treatment on the clinical outcomes of fresh and frozen embryo transfers (ETs and FETs, respectively) in infertile patients with adenomyosis. Retrospective cohort study with literature review. Peking University First Hospital. We analysed 413 cycles of 369 women with adenomyosis who underwent ETs or FETs. We performed logistic regression analysis and meta-analysis to assess the association of GnRHa pre-treatment with the clinical outcomes of ETs and FETs. The live birth rate (LBR) was compared between patients with and without GnRHa pre-treatment. The LBR was higher in the GnRHa pre-treatment group than in the non-GnRHa pre-treatment group in ETs (41.27% vs. 24.32%, p = 0.034) and FETs (40.36% vs. 20.75%, p = 0.008). The odds of achieving a live birth of women with GnRHa pre-treatment were 2.65 times higher than that of those without (95% CI: 1.19-5.92, p = 0.017) after adjusting for confounders in ETs. Similarly, the adjusted odds ratio (OR) was 2.43 (95% CI: 1.10-5.40, p = 0.029) in FETs. For the meta-analysis, eight studies met the inclusion criteria; however, only six reported the adjusted ORs. Combination of these six adjusted ORs with our results revealed that the GnRHa pre-treatment group had higher LBRs than the non-GnRHa pre-treatment group (ET: OR 1.71, 95% CI: 1.30-2.26, FET: OR 2.61, 95% CI: 1.52-4.49). In women with adenomyosis, GnRHa pre-treatment may be beneficial for LBRs following both ETs and FETs.

PHARYNGEAL AIRWAY CHANGES IN PATIENTS TREATED WITH TWINBLOCK THERAPY: CBCT STUDY

The purpose of this study was to evaluate the effect of Twinblock on pharyngeal airway. Material and Methods total CBCT record of 45 subjects of North Indian in the age range of 11-15 years were assessed.Out of these 45 subjects,25 treated skeletal class II malocclusion and 20 control Skeletal class I relationship subjects were selected.The subjects were divided into three groups control, pretreatment and posttreatment Groups.The CBCTwas used to measure the following variablesHeight,Width,length, cross-sectional areas at PNS plane, U plane, Eplane and pharyngeal airway volume. Student t test and chi-square test, linear regressiontest and Pearson correlation wereused for statistical analysis. Results-After twin block treatment pharyngeal airway measurements statistically significant difference were found in pharyngeal airway parameters except Wg, Vp and CSAp.No statistically significant difference were found between pretreatment and control group. Correlation coefficient showed negative correlation between Hpand Wp and Wn andLg as one parameter increase other parameters decreased.Rest all other parameters shows positive correlation. Conclusion-PharyngealAirway parameters were significantly increased after Twin Block Therapy in both the genders. The shape of Nasopharynx and Glossopharynxturned more elliptic in transverse plane whereas shape of Palatopharynxturned more circular.

Gardenia jasminoides fruit extract alleviates non-steroidal anti-inflammatory drug–induced gastropathy in rats

BackgroundNSAID-induced gastropathy is a health burden that requires effective intervention. Among various prevention options, Gardenia jasminoides fruit extract (GJE) has demonstrated gastroprotective effects through anti-inflammatory pathways with a wide safety margin. However, the detailed molecular mechanisms of GJE regarding mucoprotective and anti-inflammatory effects remained to be explored. Therefore, we investigated the effects of GJE on NSAID-induced gastric injury in rats, focusing on the expression of the protective factors: prostaglandin E2 (PGE2) and mucin 5AC (MUC5AC), and the aggravating factors: inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB).MethodsTwenty-four male Sprague–Dawley rats were assigned to three experimental groups (n = 8/group): the control group, the NSAIDs group receiving indomethacin to induce gastric ulcers, and the NSAIDs with GJE pretreatment (NSAIDs + GJE) group. After a two-day experimental period, the stomachs were collected for histopathological examination, immunohistochemical staining, and protein expression analysis in gastric tissue lysates.ResultsThe NSAIDs group exhibited severe neutrophil infiltration with ulcers upon gastric histopathological examination. Pretreatment with GJE attenuated NSAID-induced gastropathy, as evidenced by reduced neutrophil infiltration and decreased ulceration. Immunohistochemical staining and Western blotting demonstrated reduced expressions of PGE2 and MUC5AC, while the expressions of iNOS and NF-κB were increased following NSAID administration. In comparison to the NSAIDs group, the NSAIDs + GJE group exhibited higher expressions of PGE2 and MUC5AC and lower expressions of iNOS and NF-κB, providing evidence of the gastroprotective effects of GJE.ConclusionsPretreatment with GJE alleviated NSAID-induced gastric ulcers by increasing the expression of PGE2 and MUC5AC and decreasing the expression of iNOS and NF-κB. This study contributes to the understanding of the mechanisms by which GJE attenuates NSAID-induced gastropathy. Further studies are required to validate the effect of GJE in clinical settings.

Neurprotective Role of Amaranthus Dubius on Penicillin Induced Experimental Epileptic Rat Model by Combating the Multineurotransmitter Deficiency

Objective: The study aims to clarify the protective effects of Amaranthus dubius (AD) in penicillin (PCN)-induced experimental epilepsy models in rats. Method: In this study, twenty-four adult male Wistar albino rats, each weighing between 200-250 grams, were utilized. The rats were allocated into four groups: a control group, an Amaranthus dubius (AD) treated control group, a PCN-induced experimental epileptic rat model group, and an AD pretreated PCN-induced experimental epileptic rat model group. All groups were administered a daily oral dosage of 400 mg/kg body weight of AD aqueous leaf extract for fourteen days via an orogastric cannula. For the experimental epileptic model, PCN was injected into designated areas of the somatosensory cortex. On the concluding fifteenth day, subsequently, the rats were humanely euthanized. Tissue specimens from the cerebral cortex (CC), cerebellum (CB), caudate nucleus (CN), pons and medulla (PM), and midbrain (MB) were extracted, measured, and homogenized to facilitate subsequent biochemical analyses. Result: Pretreatment with AD has demonstrated significant changes in the levels of antioxidants and neurotransmitters in the brain. Conclusion: Amaranthus Dubius aids in combating multi-neurotransmitter deficiencies and enhances the body's antioxidant capabilities.

Dabigatran attenuates methotrexate-induced hepatotoxicity by regulating coagulation, endothelial dysfunction, and the NF-kB/IL-1β/MCP-1 and TLR4/NLRP3 signaling pathways.

This study examines Dabigatran's (Dab) capacity to mitigate methotrexate (MTX)-induced coagulation disorders and endothelial dysfunction, while exploring its effects on oxidative stress and inflammatory pathways (NF-kB/IL-1β/MCP-1, TLR4/NLRP3) in reducing hepatotoxicity. Rats were assigned to four groups: a control group receiving saline intraperitoneally (i.p.); an MTX group with a single MTX dose (20 mg/kg, i.p.) to induce hepatotoxicity; and two pretreatment groups receiving Dab orally at 15 mg/kg and 25 mg/kg for seven days before and 4 days after MTX administration. MTX-treated rats showed significant increases in liver enzymes (ALT, AST, ALP) and reductions in antioxidant enzymes (SOD, GSH), along with elevated coagulation parameters (tissue factor (TF), thrombin, fibrin, plasminogen activator inhibitor-1 (PAI-1)), leading to coagulation disorders. Endothelial dysfunction was evident with reduced eNOS expression, while inflammation increased through elevated iNOS, ICAM-1, and pro-inflammatory cytokines (MPO, NF-kB, TNF-α, IL-1β, MCP-1), alongside activation of the TLR4/NLRP3 inflammasome pathway and decreased IL-10 (p < 0.05). Immunohistochemistry revealed increased cytochrome c and caspase-3 expression, with histopathological damage. Dabigatran mitigated these effects, downregulating liver enzymes, modulating coagulation factors, restoring eNOS levels, and reducing histopathological and inflammatory markers. Dabigatran demonstrates significant therapeutic potential in alleviating methotrexate-induced hepatotoxicity through its antioxidant, anti-inflammatory, anticoagulant, and anti-apoptotic effects. Its regulation of coagulation parameters and endothelial function suggests a protective role against tissue damage, warranting further investigation.

Effects of Trimetazidine on Rat Heart Muscle during Hypoxia and Reperfusion

Objective: Trimetazidine (TMZ) is a cardioprotective drug with anti-ischemic and anti-hypoxic metabolic actions. This study aims to investigate the impact of TMZ on the contractile and recovery properties of isolated papillary heart muscle under normoxic and hypoxic conditions. Methods: Left ventricular papillary muscles were harvested from 40 Wistar rats. After a 10-minute equilibration period in a normoxic bath, contractile and relaxation responses were recorded in normoxic and hypoxic baths with varying concentrations of TMZ (0 M, 5 x 10–6 M, and 5 x 10-5 M). The specimens were then re-perfused with oxygenated Krebs-Henseleit solution (95% O2 and 5% CO2) and equilibrated for 10 minutes in a normoxic bath. Recovery contractile and relaxation responses were measured. Results: Both doses of TMZ had a negative inotropic effect on muscle (p &lt; 0.001), resulting in a limited decline in biomechanical performance in the hypoxic bath (p &lt; 0.001). However, both doses of TMZ also increased the recovery biomechanical performance compared to the control group (p &lt; 0.001). Conclusions: Under normoxic conditions, TMZ pretreatment alone did not show any cardioprotective effect. However, adding TMZ at a concentration of 5 x 10-6 M, a therapeutic level in humans, reduced ischemic contracture and improved postischemic recovery of contraction forces in both pretreated and control groups. Despite trimetazidine’s negative inotropic effect under normoxic conditions, near-therapeutic doses of the drug have significant protective effects on isolated papillary heart muscle contractility, leading to improved contractile function under hypoxic conditions.