Post-treatment Group Research Articles

Exploring the efficacy of al-hijamah (wet cupping) in managing hypertension and dyslipidemia among indonesian population: a meta-analysis

Background: In Indonesia, wet cupping therapy has been thoroughly investigated as a treatment for hypertension and dyslipidemia. Nevertheless, the outcomes across these studies are contradictory. Objectives: To appraise the effectiveness of wet cupping therapy in the management of hypertension and dyslipidemia among the Indonesian population. Methods: We examined papers sourced from Google Scholar, the Indonesian Scientific Journal Database, and Garba Rujukan Digital until September 5, 2020. These papers investigated blood pressure and lipid profile levels both pre- and post-wet cupping treatment. The collective data underwent Z-test analysis to assess associations. Results: In total, we included 26 papers examining the correlation between wet cupping therapy and blood pressure, as well as 16 papers assessing lipid profile levels. Our combined analysis revealed significantly reduced systolic blood pressure (MD: 13.86; 95% CI: 10.01, 17.71), diastolic blood pressure (MD: 6.31; 95% CI: 3.84, 8.79), and lower total cholesterol levels (MD: 21.56; 95% CI: 10.32, 32.80]) in the post-treatment group compared to the pre-treatment group. However, we were unable to elucidate the impact of wet cupping therapy on the concentrations of low-density lipoprotein and triglyceride. Conclusions: Wet cupping therapy exhibits potential efficacy in reducing blood pressure and total cholesterol levels among individuals in Indonesia. Keyword: blood pressure, dyslipidemia, hypertension, lipid profile, wet cupping therapy

Comparative Evaluation of Ion Release and Uptake of Fluoride Varnish Containing Dicalcium Phosphate Dihydrate and Casein Phosphopeptide-Amorphous Calcium Phosphate – An Experimental Approach.

The effectiveness of fluoride varnish may be restricted due to inadequate bioavailability of phosphate and calcium ions in the oral cavity. Dicalcium phosphate dihydrate and Casein phosphopeptide–amorphous calcium phosphate have exhibited ability to enhance absorption of calcium and fluoride. The present study aims to compare the remineralization potential of fluoride varnishes containing DCPD and CPP-ACP. Materials and Method: The ion release, precipitation and surface microhardness of enamel blocks were compared following topical application of various Floride varnishes. Thirty enamel blocks were divided into 3 groups following randomization that included: NaF varnish (Group A), CPP-ACP NaF varnish (Group B) and DCPD- NaF varnish (Group C). Pre- and post-treatment microhardness was evaluated using Vickers Microhardness Tester. UV-Vis Spectroscopy assessed the fluoride release at 2 hrs, 4 hrs and 6 hrs. The uptake of fluoride, calcium and phosphates were determined using SEM-EDX. The statistical significance was tested with One-way ANOVA variance for normality followed by post-hoc tests (p ≤ 0.05). Results: All the groups showed statistically significant increase in microhardness post-treatment (Group A: p=0.03, Group B, C: p=0.00). The mean increase in VHN was Group B (53.67) > Group C (34.75) > Group A (27.40). No significant difference in the F release was noted over time (p=0.00). The fluoride release over all three time intervals was Group C > Group B > Group C. Fluoride, Calcium and Phosphates showed highly significant differences between groups (p=0.00) with Group C > Group A> Group B. Conclusion: The novel NaF-DCPD Varnish displayed a promising remineralization potential, however it cannot be conclusively considered to be superior to the commercially available NaF-CPP ACP Varnish. Further in-vivo investigations need to be undertaken to determine the efficacy of NaF-DCPD varnish to determine its feasibility in clinical practice.

Exploring the protective effect of silver Croton tiglium nano-extract against azoxymethane induced toxicity in female reproductive organs in rats

Reproductive toxicity from food and environmental contaminants has greatly affected human life. Plants are a fundamental source of bioactive components for relieving the harmful effects of pollutants. Hydrazine metabolites pose health threats when they enter the food chain. Croton tiglium (C. tiglium) exhibits anti-inflammatory and anti-tumor properties. Silver nanoparticles enhance the chemical stability of C. tiglium. Reproductive toxicity of Azoxymethane (AOM) and anticancer effects of silver C. tiglium were evaluated. Thirty-six adult female rats were divided into six groups (n = 6) and treated with AOM with or without silver C. tiglium nano-extract as pre- and post-treatment. Sexual hormones and proteins were assessed under silver C. tiglium nano-extract and AOM. Histopathologically, AOM caused metaplastic myometrial endometriotic cysts and endometrial metaplasia. Silver C. tiglium in pre- and post-treated rats mitigated the carcinogenic effects of AOM. Immunohistochemically, AOM carcinogenicity was evident through moderate detection of the CK-7 tumor marker in the ovaries and uterus of the AOM-, simultaneous-, and post-treated groups. C. tiglium ameliorated this, with CK-7 slightly expressed in the pre-treated group. Furthermore, C. tiglium alleviated the negative impact on FSH, LH, and 17-β estradiol hormones. In conclusion, Silver C. tiglium nano-extract successfully prevented tumors in the ovaries and uterus of AOM-treated rats.

Oral toxicity assessment and the mitigation of lung carcinogenesis by phytol and α-bisabolol combination treatment in swiss albino mice: insights into redox enzyme modulation and caspase-dependent cell death mechanisms.

This study examined the safety and potential anti-lung cancer effects of combinations of phytol and α-bisabolol in Swiss albino mice. Both acute and subacute toxicity assessments showed that the combination of phytol and α-bisabolol is safe, with no adverse effects observed at higher concentrations. Hematological, biochemical, and histopathological tests showed no signs of toxicity in the heart, lungs, liver, spleen, and kidneys. The LD50 was greater than 2000mg/kg, indicating a large safety margin. Histopathological analysis confirmed cancer induction in the B(a)P-induced group, which had significantly altered relative lung weights. Lung weight increased slightly pre and post-treatment, but histopathology showed normal alveolar epithelium. GSH and SOD levels increased significantly in B(a)P-exposed groups, indicating an adaptive antioxidant response. CAT levels increased significantly in the post-treatment group, demonstrating the role of combination of phytol and α-bisabolol in protecting against B(a)P-induced oxidative damage. Upregulation of Bax and downregulation of Bcl-2 caused a pro-apoptotic environment, suggesting a way to inhibit malignant cell survival. Modulation of caspase-3 and caspase-9 showed the complexity of carcinogen-induced apoptotic signaling. In conclusion, phytol and α-bisabolol were found to be safe and organ-protective, and demonstrated no acute or subacute toxicity. They modulate antioxidant defenses and apoptotic pathways, which may help prevent and treat lung cancer.

B-253 Using biomarkers in recurrent renal stone formers to detect silent stones

Abstract Background Glycosaminoglycans (GAGs) protect cells from binding of calcium oxalate (CaOx) crystals to prevent CaOx stone formation. Hyaluronan (HA) is a non-sulfated GAG with crystallization-promoting activity during renal stone formation. The excretion of urinary GAGs and HA were measured in stone-formers (SF), post-treated SF, and normal controls to reveal their relationship with renal stone disease. Methods Three groups were included - active SF, post-treated SF (SF after extracorporeal shock wave lithotripsy) and normal controls with 40 subjects in each group. Early morning urine was collected for each subject. The hexuronate content of the GAGs were measured by carbazole reaction and values for GAGs were standardized against creatinine. Individual GAGs extracts were then digested sequentially with Streptomyces hyaluronidase and chondroitinase ABC to yield the HA disaccharides for analysis by high performance liquid chromatography. Results Hexuronate content of GAGs were in the order of post-treated SF < SF << normal controls. SF had an enhanced urinary excretion of HA with no increase of urinary HA in post-treated SF group. However, both the SF and post-treated SF groups had increased proportion of HA (of total GAGs) compared to normal controls. Active-SF and post-treated SF groups had lower total GAGs content but increased proportion of HA than that of the normal controls indicating that urinary GAGs and HA are probably protective/risk factors, respectively, for renal stone disease. Conclusions The higher recurrence rate of renal stone disease may be due to the presence of sub-species of GAGs, HA, that becomes an accidental participant for renal stone formation. Concomitantly, other species of charged sulfated GAGs, which are protective to the cells and prevent crystal binding, are found to be in lesser content in active SF and post-treated SF. Clinicians can use these two markers, which are easily detectable (by ELISA) for prevention and monitoring of silent renal stone formation.

Three-Year Effects of Motivational Interviewing–Enhanced Behavior Therapy for Adolescents With ADHD: A Randomized Community-Based Trial

This study reports 3-year effects of a parent-teen cognitive/behavioral treatment for adolescent attention-deficit/hyperactivity disorder (ADHD), blended with Motivational Interviewing (Supporting Teens' Autonomy Daily [STAND]), vs Usual Care (UC) in 4 community clinics. This was a randomized clinical trial with double randomization of adolescents and therapists to STAND vs UC. Participants were 278 culturally diverse adolescents diagnosed with DSM-5 ADHD and 82 community therapists. Long-term effects on outcomes and theorized mechanisms were assessed at approximately 3 years post baseline (mean age= 16.94 years, SD= 1.69): ADHD severity (parent-rated), parent-teen conflict (parent/adolescent-rated), organization, time management, and planning skills (OTP; parent-rated), treatment and school enrollment (parent/adolescent-reported), and ADHD diagnostic persistence (clinician-determined). Therapist licensure was examined as a treatment moderator. Intent-to-treat (ITT) and per protocol analyses (n = 225; participants initiating treatment after agency intake) were conducted. As in the original trial, ITT analyses indicated no long-term group by time effects. However, STAND (vs UC) led to superior long-term outcomes when therapists were licensed (22% of sample) vs unlicensed for parent-rated hyperactivity/impulsivity (d= 0.39; adolescent-rated parent-teen conflict: d= 0.27, and parent-rated OTP skills: d= 0.79). Previously reported post-treatment group differences on medication engagement were non-significant at the 3-year follow-up. Although STAND did not outperform UC overall, group by licensure interactions indicate specific long-term impacts on ADHD symptoms, executive function skills such as OTP, and parent-teen conflict, extending this trial's acute effects and replicating previous findings. Clinicians in community settings might recommend adjunctive cognitive/behavioral treatment to adolescents with ADHD to maximize long-term outcomes. However, additional efforts are needed to facilitate effective implementation by unlicensed clinicians. STAND Community Trial (STAND); https://clinicaltrials.gov; NCT02694939. Long-term Follow-up of MI-based Behavioral Intervention Delivered in Community Mental Health; https://osf.io; h5w6f. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

The impact of antioxidants on antioxidant capacity, DNA fragmentation, and chromatin quality in subfertile men: a randomized clinical trial study.

This randomized clinical trial study aims to investigate the effects of antioxidant food supplementation on the total antioxidant capacity of seminal plasma, sperm DNA fragmentation, sperm chromatin quality, and semen parameters. In this study, a total of 48 subfertile men with moderate physical activity were included. Group 1 was recommended to use the antioxidant supplements, while antioxidant food supplements were not given to Group 2. Total antioxidant capacity, sperm DNA fragmentation, sperm chromatin structure, hormone levels, physical activities, and semen parameters were evaluated before and after treatment. Total antioxidant capacity, sperm DNA fragmentation, and sperm chromatin structure were assessed using ELISA, transferase dUTP nick end labeling, and aniline blue staining, respectively. Sperm DNA fragmentation (p=0.003) and histone/protamine ratio (p<0.001) were significantly decreased in the patients receiving antioxidant treatment. There was no statistical difference in the total antioxidant capacity values of the post-treatment groups. Antioxidant therapy seems to improve sperm DNA fragmentation and histone/protamine ratios in subfertile patients. NCT06042738.

Metabolomic Effects of Liraglutide Therapy on the Plasma Metabolomic Profile of Patients with Obesity.

Liraglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP1RA), is a well-established anti-diabetic drug, has also been approved for the treatment of obesity at a dose of 3 mg. There are a limited number of studies in the literature that have looked at changes in metabolite levels before and after liraglutide treatment in patients with obesity. To this end, in the present study we aimed to explore the changes in the plasma metabolomic profile, using liquid chromatography-high resolution mass spectrometry (LC-HRMS) in patients with obesity. A single-center prospective study was undertaken to evaluate the effectiveness of 3 mg liraglutide therapy in twenty-three patients (M/F: 8/15) with obesity, mean BMI 40.81 ± 5.04 kg/m2, and mean age of 36 ± 10.9 years, in two groups: at baseline (pre-treatment) and after 12 weeks of treatment (post-treatment). An untargeted metabolomic profiling was conducted in plasma from the pre-treatment and post-treatment groups using LC-HRMS, along with bioinformatics analysis using ingenuity pathway analysis (IPA). The metabolomics analysis revealed a significant (FDR p-value ≤ 0.05, FC 1.5) dysregulation of 161 endogenous metabolites (97 upregulated and 64 downregulated) with distinct separation between the two groups. Among the significantly dysregulated metabolites, the majority of them were identified as belonging to the class of oxidized lipids (oxylipins) that includes arachidonic acid and its derivatives, phosphorglycerophosphates, N-acylated amino acids, steroid hormones, and bile acids. The biomarker analysis conducted using MetaboAnalyst showed PGP (a21:0/PG/F1alpha), an oxidized lipid, as the first metabolite among the list of the top 15 biomarkers, followed by cysteine and estrone. The IPA analysis showed that the dysregulated metabolites impacted the pathway related to cell signaling, free radical scavenging, and molecular transport, and were focused around the dysregulation of NF-κB, ERK, MAPK, PKc, VEGF, insulin, and pro-inflammatory cytokine signaling pathways. The findings suggest that liraglutide treatment reduces inflammation and modulates lipid metabolism and oxidative stress. Our study contributes to a better understanding of the drug's multifaceted impact on overall metabolism in patients with obesity.

Peripheral nesfatin-1 reduces basal brain activity but has limited effect on epilepsy-like conditions.

In this study, we investigated the effects of peripheral nesfatin-1 on basal brain activity and 4-aminopyridine (4-AP)-induced epileptiform activity, and its relationship with the electrocorticogram (ECoG) power spectrum and EEG bands. Forty-nine male Wistar rats were divided into seven groups: control sham, 4-AP (2.5 mg/kg i.p.), Nesfatin-1 (1, 2, and 4 μg/kg i.p.), Nesfatin-1 (2 μg/kg) post-treatment, and Nesfatin-1 (2 μg/kg) pre-treatment. Recordings were conducted for 70 min under ketamine/xylazine (90/10 mg/kg) anesthesia. In the post-treatment group, nesfatin-1 was injected 20 min after 4-AP induction. In the pre-treatment groups, nesfatin-1 was administered following basal recordings and before 4-AP injection. 4-AP induced epileptiform activity in all animals, peaking at 30 min. Nesfatin-1 (2 μg/kg) reduced basal brain activity (p < 0.05) and decreased alpha, delta, and theta bands in ECoG. Post-treatment of nesfatin-1 did not affect 4-AP-induced activity (p > 0.05) but increased gamma band activity (p > 0.05). Pre-treatment of nesfatin-1 reduced epileptiform activity between 50 and 60 min (p < 0.05), decreased delta bands, and increased gamma bands (p > 0.05). We conclude that peripheral nesfatin-1 modulates normal brain activity but has limited effects on abnormal discharges.

Effect of Long-Snake Moxibustion on Gut Microbiota of Patients with Ankylosing Spondylitis

Objective: The objectively was to study the effect of long-snake moxibustion intervention on gut microbiota of patients with ankylosing spondylitis (AS) by 16S rDNA sequencing technology. Methods: Thirty AS patients and 30 healthy volunteers were recruited and treated with long-snake moxibustion once a week for 12 weeks. AS patients were divided into pretreatment and posttreatment groups. VAS, BASDAI, and BASFI scores of AS patients before and after treatment were collected. 16S rDNA high-throughput sequencing technology was used to analyze the characteristics and differences of gut microbiota in AS patients before and after treatment and in healthy volunteers. Results: VAS, BASDAI, and BASFI scores of AS patients after long-snake moxibustion treatment were lower than those of pretreatment group (p < 0.05). The results of gut microbiota alpha diversity showed that Ace and Chao1 index of the posttreatment group were higher than those of the health group (p < 0.05), but there was no statistical significance in Ace and Chao1 index between the pretreatment group and the posttreatment group (p > 0.05). Beta diversity analysis showed that mild classification aggregation occurred between the health group and the pretreatment group but did not reach a significant level, and there was no significant difference between the pretreatment group and the posttreatment group. The results of species abundance showed that, at the phylum level, compared with the health group, the relative abundance of Firmicutes and Proteobacteria decreased in the pretreatment group, while the relative abundance of Bacteroidetes and Actinobacteria increased. Compared with the pretreatment group, the relative abundance of Firmicutes increased and the relative abundance of Actinobacteria decreased in the posttreatment group, but there were no statistically significant differences in the above changes (p > 0.05). At the genus level, compared with the health group, the relative abundances of Subdoligranulum in the pretreatment group were increased (p < 0.05), while the relative abundances of Bifidobacterium and Streptococcus were decreased (p < 0.05). Compared with the pretreatment group, the relative abundance of Romboutsia in the posttreatment group was increased (p < 0.05). Conclusion: Long-snake moxibustion can obviously improve the clinical symptoms of AS patients. The possible mechanism of action is related to regulating the abundance of gut microbiota, increasing beneficial bacteria, and restoring the homeostasis of gut microorganisms.

Alterations in functional brain connectivity following treatment for restless legs syndrome: The role of symptom improvement in restoring functional connectivity.

The pathophysiology of restless legs syndrome (RLS) remains incompletely understood. Although several studies have investigated the alterations of brain connectivity as one of the pathophysiological mechanisms of RLS, there are only few reports on functional connectivity changes after RLS treatment. Forty-nine patients with newly diagnosed RLS and 50 healthy controls were prospectively enrolled. The patients underwent resting-state functional magnetic resonance imaging (rs-fMRI) at baseline, and 39 patients underwent follow-up rs-fMRI, 3 months after treatment with pramipexole or pregabalin. Patients were divided into good or poor medication response groups. Functional brain connectivity was analysed using rs-fMRI and graph theoretical analysis. Significant differences in functional connectivity were observed between the RLS patients and healthy controls. The average path length, clustering coefficient, transitivity, and local efficiency were lower (2.02 vs. 2.30, p < 0.001; 0.45 vs. 0.56, p < 0.001; 3.08 vs. 4.21, p < 0.001; and 0.71 vs. 0.76, p < 0.001, respectively) and the global efficiency was higher (0.53 vs. 0.50, p < 0.001) in patients with RLS than in healthy controls. Differences in functional connectivity at the global level were also observed between post- and pre-treatment RLS patients who showed a good medication response. Transitivity in the post-treatment group was higher than that in the pre-treatment group (3.22 vs. 3.04, p = 0.007). Global efficiency was positively correlated with RLS severity (r = 0.377, p = 0.007). This study demonstrates that RLS is associated with distinct alterations in brain connectivity, which can be partially normalised following symptom management. These findings suggest that therapeutic interventions for RLS modulate brain function, emphasising the importance of symptom-focussed treatment in managing RLS.

Novel insights on microbiome dynamics during a gill disease outbreak in farmed rainbow trout (Oncorhynchus mykiss)

The generic term “Gill disease” refers to a wide range of disorders that affect the gills and severely impact salmonid aquaculture systems worldwide. In rainbow trout freshwater aquaculture, various etiological agents causing gill diseases have been described, particularly Flavobacterium and Amoeba species, but research studies suggest a more complex and multifactorial aetiology. Here, a cohort of rainbow trout affected by gill disease is monitored both through standard laboratory techniques and 16S rRNA Next-Generation Sequencing (NGS) analysis during a natural disease outbreak and subsequent antibiotic treatment with Oxytetracycline. NGS results show a clear clustering of the samples between pre- and post-treatment based on the microbial community of the gills. Interestingly, the three main pathogenic bacteria species in rainbow trout (Yersinia ruckeri, Flavobacterium psychrophilum, and Flavobacterium branchiophilum) appear to be weak descriptors of the diversity between pre-treatment and post-treatment groups. In this study, the dynamics of the gill microbiome during the outbreak and subsequent treatment are far more complex than previously reported in the literature, and environmental factors seem of the utmost importance in determining gill disease. These findings present a potential novel perspective on the diagnosis and management of gill diseases, showing the limitations of conventional laboratory methodologies in elucidating the complexity of this disease in rainbow trout. To the authors’ knowledge, this work is the first to describe the microbiome of rainbow trout gills during a natural outbreak and subsequent antibiotic treatment. The results of this study suggest that NGS can play a critical role in the analysis and comprehension of gill pathology. Using NGS in future research is highly recommended to gain deeper insights into such diseases correlating gill’s microbiome with other possible cofactors and establish strong prevention guidelines.

P2Y12 adenosine receptor inhibitors preloading among patients with non-ST-elevation acute coronary syndromes; insights from a nationwide multicenter registry.

The safety and efficacy of treatment with P2Y12 adenosine-diphosphate receptor inhibitors (P2Y12-RI) before coronary angiography among patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) are questionable. To assess the pretreatment rate with P2Y12-RI and its association with ischemic and bleeding risks among patients with NSTEACS. The study comprised patients with NSTEACS referred for coronary angiography and included in the Acute Coronary Syndrome Israeli Surveys between 2013 and 2021. Patients were divided into two groups according to the timing of P2Y12-RI loading concerning coronary angiography: pretreatment and posttreatment. The primary endpoints were 30-day major adverse cardiovascular events (MACE; composite of cardiovascular mortality, myocardial infarction, stroke, stent thrombosis, and urgent revascularization) and 1-year all-cause mortality. Of 3076 patients, 2423 (78.8%) received pretreatment with a P2Y12-RI, and 653 (21.2%) received P2Y12-RI posttreatment. Prasugrel and ticagrelor were used more in the posttreatment group compared to the pretreatment group (16% vs. 6% and 38% vs. 25%, respectively, p < 0.001 for both). No difference was observed in the rate of 30-day MACE comparing pretreatment and posttreatment (5.3% vs. 2.2%, respectively, p = 0.62). A sensitivity analysis of 30-day MACE among patients from the 2021 survey demonstrated similar results (2.5% in the posttreatment group vs. 8.0% in the pretreatment group, p = 0.13). There were no differences in 1-year all-cause mortality rates between the pretreatment and posttreatment groups (4.8% vs. 3.8%, p = 0.31). Among patients with NSTEACS referred for an invasive strategy, the P2Y12-RI posttreatment strategy was associated with similar 30-day and 1-year MACE as the pretreatment strategy. These large-scale, multicenter, real-world data provide reassurance on the safety and efficacy of delaying P2Y12-IR until after coronary stratification to improve clinical decision-making.

The Hepatoprotective Effect of a Newly Synthesized 5-Mercapto-1,2,4-Triazole Derivative based on Nalidixic Acid Against Ccl4 induced Oxidative Stress in Mice

Background: Oxidative stress plays a key role in the development of a wide range of diseases, including diabetes and cancer. Recent studies reported that the derivatives of triazole compounds have a potent antioxidant activity. Therefore, this study was designed to investigate the hepatoprotective effect of a novel newly synthesized 5-mercapto-1,2,4-triazole based on nalidixic acid [1-ethyl-3-(5-mercapto-4-(p-tolyl)-4H-1,2,4-triazol-3-yl)-7-methyl-1,8-naphthyridin] (MTTN) 3 compound against CCl4 induced oxidative stress in mice. Materials and Methods: The MTTN compound was synthesized through the interaction and then cyclization of p-tolylisothiocyanate with nalidixic acid hydrazide. By using 1 H-NMR, 13C-NMR, IR, and elemental analyses, the structure of the newly synthesized MTTN compound was identified. To investigate the hepatoprotective effect of this compound, forty BALB/c mice were divided into four groups (n=10) as follows: the control group, the oxidative stress-induced group, which was intraperitoneally injected with 10% CCl4 (2 mL/kg), one pre-treatment group, which was treated orally with 200 mg/kg of MTTN compound for 8 days before being treated with CCl4 at day 8, and one post-treatment group, which was treated orally with 200 mg/kg of MTTN compound for 8 days simultaneously with CCl4 co-administration at days 3 and 5. At day 9, animals were scarified and serum and liver samples were collected. Results: CCl4 administration caused significant hepatotoxicity as evidenced by marked elevation in the serum activity of the liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and high blood cholesterol levels. Furthermore, the hepatic malondialdehyde (MDA) level, a marker of lipid peroxidation, was increased with CCl4 administration that was associated with a decrease in the hepatic superoxide dismutase (SOD) and catalase (CAT) activities (p &lt; 0.05). However, pre and post-treatment with the new newly synthesized MTTN compound significantly reduced the serum levels of AST, ALT, and cholesterol and reduced hepatic oxidative stress as indicated by the decrease in the hepatic MDA level and the increases in the SOD and CAT activities (p &lt; 0.05). Conclusion: This study suggests that the newly synthesized MTTN compound has a potent antioxidant property and can protect against CCl4-induced liver injury. Thus, with more clinical studies, this compound may be used as effective therapeutic agents against oxidative stress related diseases.

A comparative study of microbial changes in dental plaque before and after single- and multiappointment treatments in patients with severe early childhood caries

BackgroundThe status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment.MethodsForty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology.Results(1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P < 0.05), and the remaining alpha diversity index did not significantly differ between the 2 groups (P > 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P < 0.05). (2) The core flora existed in both the pre- and posttreatment groups, and the proportion of their flora abundance could be altered depending on the caries status of the children in both groups. Leptotrichia abundance was significantly (P < 0.05) lower at 7 days posttreatment in both the single- and multiappointment groups. Corynebacterium and Corynebacterium_matruchotii were significantly more abundant in the C1_1M and C1_3M groups than in the C1 and C1_7D groups (P < 0.05). Streptococcus, Haemophilus and Haemophilus_parainfluenzae were significantly more abundant in the C1_7D group than in the other groups (P < 0.05).ConclusionA single session of treatment under general anaesthesia can cause dramatic changes in the microbial community structure and composition within 7 days after treatment, whereas treatment over multiple appointments may cause slow changes in oral flora diversity.

The Effect of Intranasal Plus Transcranial Photobiomodulation on Neuromuscular Control in Individuals with Repetitive Head Acceleration Events.

Objective: This proof-of-concept study was to investigate the relationship between photobiomodulation (PBM) and neuromuscular control. Background: The effects of concussion and repetitive head acceleration events (RHAEs) are associated with decreased motor control and balance. Simultaneous intranasal and transcranial PBM (itPBM) is emerging as a possible treatment for cognitive and psychological sequelae of brain injury with evidence of remote effects on other body systems. Methods: In total, 43 (39 male) participants, age 18-69 years (mean, 49.5; SD, 14.45), with a self-reported history of concussive and/or RHAE and complaints of their related effects (e.g., mood dysregulation, impaired cognition, and poor sleep quality), completed baseline and posttreatment motor assessments including clinical reaction time, grip strength, grooved pegboard, and the Mini Balance Evaluation Systems Test (MiniBEST). In the 8-week interim, participants self-administered itPBM treatments by wearing a headset comprising four near-infrared light-emitting diodes (LED) and a near-infrared LED nasal clip. Results: Posttreatment group averages in reaction time, MiniBEST reactive control subscores, and bilateral grip strength significantly improved with effect sizes of g = 0.75, g = 0.63, g = 0.22 (dominant hand), and g = 0.34 (nondominant hand), respectively. Conclusion: This study provides a framework for more robust studies and suggests that itPBM may serve as a noninvasive solution for improved neuromuscular health.

Impact of IL-6 and IL-6r variants on HIV-1 susceptibility and progression to AIDS: a case-control study in a Moroccan population

Interleukin-6 (IL-6), a pro-inflammatory cytokine, is an important regulator of the inflammatory immune response. We aimed to assess the association of common single nucleotide polymorphisms (SNPs) in IL-6 (rs1800795 G > C, rs1800797 A > G) and interleukin-6 receptor (IL-6R) (rs2228145 A > C) genes with HIV-1 infection, AIDS progression, and response to treatment. In this case-control study involving 199 individuals living with HIV-1 and 200 HIV-uninfected controls, we conducted genotyping of IL-6/IL-6R SNPs using TaqMan real-time PCR assays. Soluble IL-6 levels were measured using ELISA. No associations were found between the investigated SNPs and HIV infection. However, a significant association was noted between the C-G and G-A haplotypes and susceptibility to HIV-1 infection. Additionally, a significant association was revealed between HIV-1 RNA viral loads and IL-6 SNP G > C in the post-treatment HIV group. Interestingly, we observed a significant association between the investigated SNPs and protection against progression to AIDS, namely the IL-6 G > A SNP in its recessive model and the IL-6R A > C SNP in its codominant and dominant models. Nevertheless, we found no significant differences between IL-6 levels and the different genotypes and alleles of the IL-6 gene either before or after combination antiretroviral therapy. IL-6 promoter haplotypes are associated with susceptibility to HIV-1 infection. Furthermore, IL-6 A > G and IL-6R A > C polymorphisms have been associated with protection against AIDS progression. Interestingly, the IL-6 G > C SNP may affect the response to treatment in people living with HIV-1.

Integrated analysis of single-cell and bulk RNA sequencing data reveals a myeloid cell-related regulon predicting neoadjuvant immunotherapy response across cancers

BackgroundImmunotherapy has brought about a paradigm shift in the treatment of cancer. However, the majority of patients exhibit resistance or become refractory to immunotherapy, and the underlying mechanisms remain to be explored.MethodsSing-cell RNA sequencing (scRNA‑seq) datasets derived from 1 pretreatment and 1 posttreatment achieving pathological complete response (pCR) patient with lung adenocarcinoma (LUAD) who received neoadjuvant immunotherapy were collected, and pySCENIC was used to find the gene regulatory network (GRN) between cell types and immune checkpoint inhibitor (ICI) response. A regulon predicting ICI response was identified and validated using large‑scale pan-cancer data, including a colorectal cancer scRNA‑seq dataset, a breast cancer scRNA‑seq dataset, The Cancer Genome Atlas (TCGA) pan-cancer cohort, and 5 ICI transcriptomic cohorts. Symphony reference mapping was performed to construct the myeloid cell map.ResultsThirteen major cluster cell types were identified by comparing pretreatment and posttreatment patients, and the fraction of myeloid cells was higher in the posttreatment group (19.0% vs. 11.8%). A PPARG regulon (containing 23 target genes) was associated with ICI response, and its function was validated by a colorectal cancer scRNA‑seq dataset, a breast cancer scRNA‑seq dataset, TCGA pan-cancer cohort, and 5 ICI transcriptomic cohorts. Additionally, a myeloid cell map was developed, and cluster I, II, and III myeloid cells with high expression of PPARG were identified. Moreover, we constructed a website called PPARG (https://pparg.online/PPARG/ or http://43.134.20.130:3838/PPARG/), which provides a powerful discovery tool and resource value for researchers.ConclusionsThe PPARG regulon is a predictor of ICI response. The myeloid cell map enables the identification of PPARG subclusters in public scRNA-seq datasets and provides a powerful discovery tool and resource value.

Metformin-induced changes of the gut microbiota in patients with type 2 diabetes mellitus: results from a prospective cohort study.

The influence of the microbiota on hypoglycemic agents is becoming more apparent. The effects of metformin, a primary anti-diabetes drug, on gut microbiota are still not fully understood. This prospective cohort study aims to investigate the longitudinal effects of metformin on the gut microbiota of 25 treatment-naïve diabetes patients, each receiving a daily dose of 1500 mg. Microbiota compositions were analyzed at baseline, and at 1, 3, and 6 months of medication using 16S rRNA gene sequencing. Prior to the 3-month period of metformin treatment, significant improvements were noted in body mass index (BMI) and glycemic-related parameters, such as fasting blood glucose (FPG) and hemoglobin A1c (HbA1c), alongside homeostasis model assessment indices of insulin resistance (HOMA-IR). At the 3-month mark of medication, a significant reduction in the α-diversity of the gut microbiota was noted, while β-diversity exhibited no marked variances throughout the treatment duration. The Firmicutes to Bacteroidetes ratio. markedly decreased. Metformin treatment consistently increased Escherichia-Shigella and decreased Romboutsia, while Pseudomonas decreased at 3 months. Fuzzy c-means clustering identified three longitudinal trajectory clusters for microbial fluctuations: (i) genera temporarily changing, (ii) genera continuing to decrease (Bacteroides), and (iii) genera continuing to increase(Lachnospiraceae ND3007 group, [Eubacterium] xylanophilum group, Romboutsia, Faecalibacterium and Ruminococcaceae UCG-014). The correlation matrix revealed associations between specific fecal taxa and metformin-related clinical parameters HbA1c, FPG, Uric Acid (UA), high-density lipoproteincholesterol (HDL-C), alanine aminotransferase (ALT), hypersensitive C-reactive protein (hs-CRP), triglyceride (TG) (P < 0.05). Metacyc database showed that metformin significantly altered 17 functional pathways. Amino acid metabolism pathways such as isoleucine biosynthesis predominated in the post-treatment group. Metformin's role in glucose metabolism regulation may primarily involve specific alterations in certain gut microbial species rather than an overall increase in microbial species diversity. This may suggest gut microbiota targets in future studies on metabolic abnormalities caused by metformin.

Short-term, nonsurgical periodontal therapy boosts interleukin-12 levels and reduces oral cancer risk.

Cytokines, including interleukin-12 (IL-12), are proteins that regulate cell survival, proliferation, differentiation, and function. IL-12 is a heterodimeric proinflammatory cytokine. It possesses tumoricidal properties and promotes M1 macrophage polarization and IFN-γ production by T helper (Th1) cells, which in turn stimulates the antitumor cytotoxic cluster of eight positive (CD8+) and natural killer cells, therefore activating an effector immune response against tumor cells. Herein, the IL-2 levels of 60 patients with generalized chronic periodontitis (GCP) were assessed. Plaque index, gingival index, pocket probing depth, bleeding on probing percentage (BOP %), and clinical attachment loss were the clinical indicators reported. Patients with GCP in the pretreatment group had substantially lower mean IL-12 levels than those in the post-treatment group. Short-term, nonsurgical treatment (NST) considerably improved periodontal indices and increased IL-12 levels, thereby reducing oral cancer risk. NST is a cost-effective and accessible cancer prevention procedure for general dentists.