Post-treatment Group Research Articles

A comparative study on tensile strength of various thermoplastic polymers sheets following thermoforming on a pre-treatment and post-treatment maxillary model of a patient: an in vitro study.

Thermoplastic polymers show alteration in their mechanical properties after thermoforming on a dental model. The purpose of this in-vitro study was to evaluate the tensile strength of different thermoplastic polymer sheets thermoformed on a pre-treatment (moderate crowding) and post-treatment (well-aligned) maxillary model of a patient. Forty maxillary models (Twenty Pre-treatment & twenty Post-treatment of uniform dimension) were made by duplicating them using alginate Hydrogum 5 (Zhermack). Samples were then divided into eight groups of 5 samples each. The thermoplastic sheets Imprelon® (Scheu-Dent), AVAC R® (Jaypee), Placa Crystal® (BioART), EZ-VAC® (3A Medes)-1.0mm thick were thermoformed on these models respectively. The sample was retrieved using ceramic bur mounted on a straight hand-piece and subjected for testing using TINIUS Olsen 10ST micro universal testing machine and recorded. There was no statistically significant difference (P > .05) in tensile strength of thermoformed thermoplastic polymer sheets between pre-treatment and post-treatment maxillary model. Tensile strength of EZ-VAC (3A Medes) showed higher variation between pre-treatment and post-treatment maxillary model though it was found to be statistically insignificant (P > .05). Significant difference (P < .05) was seen between groups when they were compared separately among pre-treatment and post-treatment models. Placa Crystal (BioART) among the pre-treatment group, EZ - VAC (3A Medes) among the post-treatment group, showed highest tensile strength. Results of the study highlights the necessity to test materials in conditions which stands in accordance with the clinical scenario to a considerable extent and also emphasizes the need for further study in aligner.

Exploring oxidative stress, immunological and metabolic biomarkers in dairy cows with postpartum pyometra.

Pyometra is a prevalent and severe infectious disease that affects the reproductive systems of cattle worldwide. This study's main goal was to investigate the biomarkers for oxidative stress (OS), adiponectin, leptin and neopterin (NPT) in cows suffering from postpartum pyometra. The study also aimed to determine which bacteria were most commonly implicated in the development of the disease. A total of 74 cows with pyometra were examined and compared to a control group of healthy cows (n = 20). In comparison to the healthy control and post-treatment groups, the pyometra group showed higher mean values of leptin, adiponectin and malondialdehyde (MDA). In contrast, the glutathione (GSH) and superoxide dismutase (SOD) mean values were lower in the pyometra group as compared to the post-treatment and control groups. NPT levels in the post-treatment groups were lower than those in cows with pyometra but comparable to the healthy control group (p > .05). When compared to the other biomarkers, NPT, leptin and adiponectin showed higher sensitivity and specificity in identifying pyometra cases (AUC ≥0.99). The predominant bacterial isolates from the ptomtra-affected cows consisted of Escherichia coli (N = 29; 39.2%), Arcanobacterium pyogenes (N = 27; 36.5%) and Fusobacterium necrophorum (N = 13; 17.6%). Mixed infection was determined in nine samples (12.2%). Conclusively, OS, adiponectin, leptin and NPT play crucial roles in comprehending the development of postpartum pyometra in cows and have the potential to serve as biomarkers for the disease.

Immunologic Predictors of Vaccine Responsiveness in Patients With Lymphoma and Chronic Lymphocytic Leukemia.

Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. Severe acute respiratory syndrome coronavirus 2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic messenger RNA vaccine response in retrospective and prospective cohorts with lymphoma and chronic lymphocytic leukemia, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active treatment, but nonresponse was also common within observation and posttreatment groups. Total immunoglobulin A and immunoglobulin M correlated with successful vaccine response. In individuals treated with anti-CD19-directed chimeric antigen receptor-modified T cells, nonresponse was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to individualize vaccine timing.

Targeting Breast Cancer with N-Acetyl-D-Glucosamine: Integrating Machine Learning and Cellular Assays for Promising Results.

Breast cancer is a common cancer with high mortality rates. Early diagnosis is crucial for reducing the prognosis and mortality rates. Therefore, the development of alternative treatment options is necessary. This study aimed to investigate the inhibitory effect of N-acetyl-D-glucosamine (D-GlcNAc) on breast cancer using a machine learning method. The findings were further confirmed through assays on breast cancer cell lines. MCF-7 and 4T1 cell lines (ATCC) were cultured in the presence and absence of varying concentrations of D-GlcNAc (0.5 mM, 1 mM, 2 mM, and 4 mM) for 72 hours. A xenograft mouse model for breast cancer was established by injecting 4T1 cells into mammary glands. D-GlcNAc (2 mM) was administered intraperitoneally to mice daily for 28 days, and histopathological effects were evaluated at pre-tumoral and post-tumoral stages. Treatment with 2 mM and 4 mM D-GlcNAc significantly decreased cell proliferation rates in MCF-7 and 4T1 cell lines and increased Fas expression. The number of apoptotic cells was significantly higher than untreated cell cultures (p < 0.01 - p < 0.0001). D-GlcNAc administration also considerably reduced tumour size, mitosis, and angiogenesis in the post-treatment group compared to the control breast cancer group (p < 0.01 - p < 0.0001). Additionally, molecular docking/dynamic analysis revealed a high binding affinity of D-GlcNAc to the marker protein HER2, which is involved in tumour progression and cell signalling. Our study demonstrated the positive effect of D-GlcNAc administration on breast cancer cells, leading to increased apoptosis and Fas expression in the malignant phenotype. The binding affinity of D-GlcNAc to HER2 suggests a potential mechanism of action. These findings contribute to understanding D-GlcNAc as a potential anti-tumour agent for breast cancer treatment.

Changes in the neutrophil-to-lymphocyte ratio (NLR) as predictive values for metastatic gastric cancer patients with PD-1 inhibitors

BackgroundThe combination of immunotherapy and chemotherapy can improve the survival of metastatic gastric cancer (MGC) patients based on checkmate 649 and Orential 16. The neutrophil-to-lymphocyte ratio (NLR) in the pretreatment period can be used as a prognostic indicator in patients receiving immune checkpoint inhibitors (ICIs) to treat different cancers. However, no study has yet explored the relationships between NLR changes during PD-1 treatment and patient survival.MethodFirst, we enrolled patients diagnosed with MGC under anti-PD-1-based treatments from October 1st, 2015 to December 31st, 2020 at the Chinese PLA General Hospital. These patients were stratified regarding their baseline NLR and variants of NLR. Then we explored the association between relative NLR changes and other clinical features with the overall survival (OS) and progression-free survival (PFS) of patients treated with immunotherapy using multivariate Cox analysis.ResultsA total of 137 patients were enrolled in the present study. We categorized patients into decreased (ΔNLR < 0) and increased (ΔNLR ≥ 0) post-treatment NLR groups. The median OS and PFS were 12.3 months and 7.8 months for patients with ΔNLR < 0, respectively, compared to 7.5 months and 4.3 months for patients with ΔNLR ≥ 0 (both p < 0.05). The ORR was 41.8% in the ΔNLR < 0 group, higher than the ΔNLR ≥ 0 group (ORR = 24.3%). Patients with both NLR ≥ 3.23 and ΔNLR ≥ 0 had a significantly increased risk of death (HR: 2.349, 95% CI: 1.701 – 3.243, p < 0.001) and disease progression (HR: 2.297, 95% CI: 1.666 – 3.167, p < 0.001) compared to patients with NLR < 3.23 and ΔNLR < 0. Patients with either NLR ≥ 3.23 or ΔNLR ≥ 0 showed an intermediate risk of death (HR: 2.626, 95% CI: 1.660 – 4.155, p < 0.001) and progression (HR: 2.554, 95% CI: 1.590 – 4.101, p < 0.001). The ORR (50.0%) and DCR (91.2%) was higher in the NLR < 3.23 and ΔNLR < 0 group compared to other combination groups (both p < 0.05).ConclusionThe combination of NLR changes after anti-PD-1 treatment with the baseline NLR was significantly correlated with patient survival and could be used to categorize patients into high- and low-risk groups. Finally, prospectively designed clinical trials are required to substantiate our current findings.

Alpha-7 Nicotinic Receptor Agonist Protects Mice Against Pulmonary Emphysema Induced by Elastase.

Pulmonary emphysema is a primary component of chronic obstructive pulmonary disease (COPD), a life-threatening disorder characterized by lung inflammation and restricted airflow, primarily resulting from the destruction of small airways and alveolar walls. Cumulative evidence suggests that nicotinic receptors, especially the α7 subtype (α7nAChR), is required for anti-inflammatory cholinergic responses. We postulated that the stimulation of α7nAChR could offer therapeutic benefits in the context of pulmonary emphysema. To investigate this, we assessed the potential protective effects of PNU-282987, a selective α7nAChR agonist, using an experimental emphysema model. Male mice (C57BL/6) were submitted to a nasal instillation of porcine pancreatic elastase (PPE) (50µl, 0.667IU) to induce emphysema. Treatment with PNU-282987 (2.0mg/kg, ip) was performed pre and post-emphysema induction by measuring anti-inflammatory effects (inflammatory cells, cytokines) as well as anti-remodeling and anti-oxidant effects. Elastase-induced emphysema led to an increase in the number of α7nAChR-positive cells in the lungs. Notably, both groups treated with PNU-282987 (prior to and following emphysema induction) exhibited a significant decrease in the number of α7nAChR-positive cells. Furthermore, both groups treated with PNU-282987 demonstrated decreased levels of macrophages, IL-6, IL-1β, collagen, and elastic fiber deposition. Additionally, both groups exhibited reduced STAT3 phosphorylation and lower levels of SOCS3. Of particular note, in the post-treated group, PNU-282987 successfully attenuated alveolar enlargement, decreased IL-17 and TNF-α levels, and reduced the recruitment of polymorphonuclear cells to the lung parenchyma. Significantly, it is worth noting that MLA, an antagonist of α7nAChR, counteracted the protective effects of PNU-282987 in relation to certain crucial inflammatory parameters. In summary, these findings unequivocally demonstrate the protective abilities of α7nAChR against elastase-induced emphysema, strongly supporting α7nAChR as a pivotal therapeutic target for ameliorating pulmonary emphysema.

Effects of polyphenolic maqui (Aristotelia chilensis) extract on the inhibition of NLRP3 inflammasome and activation of mast cells in a mouse model of Crohn's disease-like colitis.

Crohn's disease (CD) involves activation of mast cells (MC) and NF-кB in parallel with the PPAR-α/NLRP3 inflammasome/IL-1β pathway in the inflamed colon. Whether polyphenols from maqui (Aristotelia chilensis) represent a natural alternative treatment for CD is unclear. Therefore, we used an animal model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD-like colitis to investigate protective effects of maqui extract through monitoring NLRP3 inflammasome and MC activation in colon tissue. Maqui extract was administered via orogastric route to mice after (post-Treatment group) or prior (pre-Treatment group) to TNBS-induction. Colon pathology was characterized by histoarchitectural imaging, disease activity index (DAI), and assessing NF-кB, p-NF-кB, PPAR-α/NLRP3 expression and IL-1β levels. Compared to mice treated with TNBS alone administration of anthocyanin-rich maqui extract improved the DAI, colon histoarchitecture and reduced both colon wet-weight and transmural inflammation. Induction with TNBS significantly increased colonic NLPR3 inflammasome activation, while co-treatment with maqui extract (either post- or pre-Treatment) significantly downregulated NLRP3, ASC and caspase-1 levels, which manifested as reduced colonic IL-1β levels. Supplemented maqui extract marginally diminished NF-кB activity in epithelial cells but reached statistical significance in immune cells (as judged by decreased NF-кB phosphorylation). PPAR-α signaling was largely unaffected by Maqui whereas MC infiltration into the colon mucosa and submucosa decreased and their level of degranulation was suppressed. These outcomes show the post- and pre- Treatment effect of a polyphenolic extract rich in anthocyanins from maqui the acute phase of TNBS- induced CD-like colitis is linked to suppression of the NLRP3 inflammasome and reduced MC responses. These data indicate that maqui extract represents a potential nutraceutical for the treatment of inflammatory bowel disease (IBD).

Comparison of SPAG11A gene expression in infertile men with grade 1 and 2 varicocele before and after treatment.

Sperm Associated Antigen 11A (SPAG11A) protein is a family of the epididymis-specific secretory proteins implicated in sperm maturation and function. Varicocele might cause pathophysiological difficulties in the testis and epididymis, with a harmful effect on the environment for spermatogenesis and sperm maturation. The aim of this study was to evaluate the expression level of the SPAG11A gene and sperm parameters in infertile men with grade 1 and 2 varicocele before and after treatment. Semen specimens were collected from 20 infertile men with varicocele pre-and post-treatment and 10 healthy volunteers. Semen analysis was conducted according to world health organization guidelines. Real time PCR (qRT-PCR) reaction was applied for determination of SPAG11A mRNA expression. The results showed that there was a significant difference between the concentration and normal morphology between pre- and post-treatment groups and the controls. There were significant differences between pre-treatment and control groups in terms of progressive and non-progressive mobility. SPAG11A mRNA levels were significantly lower in the pre-treatment group than in healthy control subjects (p=0.007). There was no statistically significant difference in the expression of SPAG11A as well as semen parameters in the post-treatment group compared to the pre-treatment group. SPAG11A gene expression and semen parameters may be affected by varicocele. Whether varicocele treatment is an effective approach to reduce the adverse effect of this disease on SPAG11A expression and semen parameters needs further investigation.

Label-free quantitative proteomic profiling reveals differential plasma protein expression in patients with obesity after treatment with liraglutide.

Treatment and management of obesity is clinically challenging. The inclusion of GLP-1 receptor agonists (GLP1RA) in the medical management of obesity has proven to be efficacious. However, mechanisms underlying the molecular changes arising from GLP1RA treatment in patients with obesity remain to be elucidated. A single-center, prospective study was undertaken to evaluate the changes in the plasma proteins after liraglutide 3 mg therapy in twenty patients (M/F: 7/13) with obesity (mean BMI 40.65 ± 3.7 kg/m2). Anthropometric and laboratory parameters were measured, and blood samples were collected at two time points: baseline, before initiating treatment (pretreatment group, PT), and after three months of receiving the full dose liraglutide 3 mg (posttreatment group, PoT). An untargeted label-free LC MSMS mass spectrometric approach combined with bioinformatics and network pathway analysis was used to determine changes in the proteomic profiles. The mean age of the study participants was 36.0 ± 11.1 years. A statistically significant change was observed in weight, BMI and HbA1c levels between the PT and PoT groups (paired t-test, P < 0.001). A significant dysregulation was noted in the abundances of 151 proteins (31 up and 120 downregulated) between the two groups. The potential biomarkers were evaluated using receiver operating characteristic (ROC) curves. The top ten proteins (area under the curve (AUC) of 0.999 (95% CI)) were identified as potential biomarkers between PT and PoT groups and included Cystatin-B, major vault protein, and plastin-3, which were upregulated, whereas multimerin-2, large ribosomal P2, and proline-rich acidic protein 1 were downregulated in the PoT group compared with the PT group. The top network pathway identified using ingenuity pathway analysis (IPA), centered around dysregulation of MAPK, AKT, and PKc signaling pathways and related to cell-to-cell signaling and interaction, cellular assembly and organization, cellular compromise and a score of 46 with 25 focus proteins. Through label-free quantitative proteomic analysis, our study revealed significant dysregulation of plasma proteins after liraglutide 3 mg treatment in patients with obesity. The alterations in the proteomic profile between the PT and PoT groups demonstrated a decrease in levels of proteins involved in inflammation and oxidative stress pathways. On the other hand proteins involved in the glycolytic and lipolytic metabolic pathways as well as those participating in cytoskeletal and endothelial reorganization were observed to be increased. Understanding actions of liraglutide at a molecular and proteomic levels provides a holistic look into how liraglutide impacts metabolism, induces weight loss and improves overall metabolic health.

Targeting Sensory Systems in the Treatment of Dystonia: Outcomes from a Case Series

Substantial scientific evidence has been gathered on the pathophysiology of dystonia, leading to proposed theoretical treatment protocols for rehabilitating patients with this disorder. This study aimed to assess patient outcomes following the application of novel functional neurology treatment protocols based on basic neuroscience research. A consecutive case series of patients diagnosed with dystonia and treated in a private practice setting was studied for their response to neural rehabilitation techniques based on published basic neuroscience research. Sensory stimulation techniques including non-invasive spinal cord stimulation, vestibular nerve neuromodulation based on targeted skull vibration and stimulation of reciprocal inhibitory nerve activity of dystonic muscles was used as novel add on therapy to standard care. The subjects included 6 cases of cervical dystonia and 3 cases of more generalized dystonia. The proposed rehabilitation procedures were explained in detail to the patients, including the investigational nature of these procedures, and written informed consent was obtained from each patient prior to treatment. Based on the comparison of total dystonia scores upon admission and prior to treatment with total dystonia scores at the completion of a course of care, all 9 patients in this case series demonstrated improvement in their dystonic symptoms after treatment. The group average pre-treatment dystonia score was 11.4, while the post-treatment group averaged dystonia score was 5.2 points. This represents a moderate, but clinically important improvement in global dystonia scores in a series of 9 patients treated in a private practice setting. Considering that dystonia is highly resistant to treatment, the improvement seen in this case series suggests that the methods involved warrant further investigation in a more formal research setting. The clinically meaningful improvements (approximately 50% for the group average) seen in these cases argue for more research into the role of the sensory systems in both the pathophysiology and treatment of dystonic conditions.

Whey preparation as an adjuvant to minimise the Intestinal inflammatory status in mucositis rat model

To study the effect of Whey Preparation on intestinal mucositis, model developed by administration of single dose of etoposide (60mg/Kg body wt., i.p). The experimental procedure included Adult albino rats (10±1 week old) of Wistar strain (n=30, 6/group). Freshly prepared whey preparation-(100 and 200mg/Kg/body wt.) was administered by orogastric gavage- Pre, both pre and post etoposide injection. Effectiveness of whey preparation was determined by estimating the biochemical parameters including intestinal Tumor Necrosis Factor-α, Interleukin-6, sodium potassium ATPase, inflammatory markers- Cyclooxygenase and Myeloperoxidase along with Nitric Oxide and reduced Glutathione with and without intervention after 72 hrs. of etoposide injection. There was a significant increase in the Tumor Necrosis Factor –α, Interleukin-6 levels and extent of apoptosis in etoposide controls. Etoposide administration caused a significant decreased the activity of Na+-K+ ATPase and reduced glutathione levels in intestinal tissue. However, in the post treatment groups, Tumor Necrosis Factor–α, Interleukin-6 as well as extent of apoptosis were reverted to normal after whey preparation administration.Whey Preparation gavage in both the study groups- pre and both pre and post etoposide exposure showed that intervention was able to preserve/ prevent changes in the biochemical activity. The results support the WP potentials to reduce the deleterious effects of etoposide on normal cells, which leads to mucositis.

Hepatoprotective Effect of Alcoholic Extract of Ficus carica Leaves ‎Against ‎‎Cypermethrin-Induced Liver Toxicity in Male Albino Rats

Cypermethrin (CYP), a synthetic pyrethroid, is recognized for its insecticidal properties but ‎poses potential risks of hepatotoxicity. In traditional medicine, Ficus (F.) carica (common ‎fig) leaves have historically been used for various therapeutic applications. This study ‎aimed to evaluate the hepatoprotective effect of the methanolic extract of F. carica‎‎ leaves ‎against CYP-induced liver damage in adult male albino rats (Rattus norvegicus). The ‎animals (n=30), 8-12 weeks old ‎and weighing 200-250 g‎, were randomly divided into five ‎experimental groups (n=6) and treated as follows: the negative control group received ‎distilled water; the CYP-Only group was exposed to 4.74 mg/kg BW for 45 days; the ‎CYP+post-treatment group received the same CYP dosage followed by F. carica‎‎ methanolic ‎leaf extract at 500 mg/kg BW orally for two weeks; the pre-treatment+CYP group received ‎ ‎F. carica‎‎ methanolic leaf extract at 500 mg/kg BW orally for two weeks followed by CYP ‎exposure for 45 days; and the F. carica‎‎ extract-Only group was administered the methanolic ‎leaf extract at 500 mg/kg BW orally for two weeks. At the end of the experiment, serum and ‎liver samples were analyzed for biochemical and histopathological changes. CYP-Only ‎exposed group showed significantly increased serum alanine aminotransferase (ALT) and ‎alkaline phosphatase (ALP) and caspase-3 levels (P&lt;0.05). Histopathological examination ‎in group exposed CYP only revealed liver damages as evidenced by central vein congestion, ‎scattered perivascular mononuclear cell infiltration, prominence of ‎Kupffer cells, nuclear ‎pyknosis, and severe hepatocytic necrosis. Treatment with F. carica‎‎ leaf extract, either ‎before or after CYP exposure, as well as solely with F. carica‎‎ leaf ‎‎extract, ameliorated both ‎the biochemical and histological indices of liver ‎damage. The findings suggest that the ‎methanolic extract of F. carica‎‎ leaves provides promising hepatoprotective effects against ‎CYP-induced liver damage in albino rats, likely via its antioxidative properties‎‎.

Harnessing the neuroprotective effect of oral administration of benfotiamine in MPTP induced Parkinson's disease in rats

The study was performed to evaluate the neuroprotective effects of Benfotiamine (BFT) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) in rats. The rats were given daily doses of BFT (100 mg/kg, 200 mg/kg) through oral administration for 42 days. The rats were given a single bilateral dosage of MPTP (0.1 mg/nostril) intranasally once before the drug treatment to induce PD. On day 42, the animals were subjected to various behavioral paradigms. Post-treatment with BFT for 42 days significantly improved the motor and nonmotor fluctuations of MPTP. The results demonstrated that treatment with BFT ameliorated MPTP-induced disorders in behavior, body balance, and dopamine levels in the mid-brain. Among the post-treated groups, a high dose of BFT was the most effective treatment. Mean values are indicated in ±SEM, n = 5***(p < 0.001) when compared with the vehicle control, n = 5 ### (p < 0.001) when compared with the disease control; (p < 0.001) when compared with the BFT per se; (p < 0.001) when compared with the low dose of BFT; (p < 0.001) when compared with the high dose of BFT. Our finding suggests that BFT contributed to superior antioxidant, and anti-inflammatory and could be a novel therapeutic method for PD management. In conclusion, BFT could be a potential drug candidate for curbing and preventing PD.

Restoring Memory Function in a Diabetic Mice Model

AbstractBackgroundDiabetes mellitus affects memory function in Alzheimer’s disease (Baglietto‐Vargas et al., 2016). Quercetin (Qt) and vitamin (Vit E) possesses anti‐inflammatory, memory enhancing and anti‐diabetic activities (Bui and Nguyen, 2017). This study explored the effects of administering both quercetin and vitamin E against cognitive deficits and neuroinflamation in high‐fat‐diet (HFD) and streptozotocin (HS)‐induced diabetic miceMethodNinety male mice (n = 15) were divided into six groups and fed with HFD except the normal group for 28 days. Diabetes was induced by STZ (50 mg/kg intraperitoneally) on day 22. Weight and blood glucose levels were taken weekly. On day 15, mice in the pretreatment groups (PQt 12.5 + Vit E 200 mg/kg and PQt 25 + Vit E) commenced treatment while on day 29, mice in the posttreatment groups (PtQt 12.5 + Vit E and PtQt 25 + Vit E) commenced treatment till day 42. Memory function (Y‐maze and NORT) was performed. The hippocampus of the animal brains were harvested for biochemical assays using ELISA (acetylcholinesterase enzyme (AChE), insulin, interleukin‐ 4 (IL‐4), interleukin‐6 (IL‐6) and tumor necrosis factor alpha (TNF‐α). Immunohistochemistry was used in detecting the expression of IBA‐1.ResultQuercetin and vitamin E significantly decreased the weight, glucose, insulin, and AChE levels in the HS‐induced mice. Memory function was restored by this combination. IL‐6 was decreased in PQt 25 + V and PtQt 25 +V; TNF‐α was decreased in PQt 25 + V and PtQt 12.5 +V while IL‐4 levels were increased in PQt 25 + V and PtQt 25 +V compared to the HS group. IBA‐1 was scarcely expressed in the PQt 12.5 mg/kg and PtQt (12.5 and 25 mg/kg) group compared to the HSgroup.ConclusionAdministering quercetin and vitamin E restored memory function through decreasing the activity of pro‐inflammatory mediators, increasing the activity of anti‐inflammatory mediators and decreasing microglial activation in HS‐induced mice.REFERENCES:Baglietto‐Vargas D, Shi J, Yaeger DM, Ager R, LaFerla FM. Diabetes and Alzheimer’s disease crosstalk. Neuroscience &amp; Biobehavioral Reviews. 2016 May 1;64:272‐87.Bui, T. T., &amp; Nguyen, T. H. (2017). Natural product for the treatment of Alzheimer’s disease. Journal of Basic and Clinical Physiology and Pharmacology, 28(5), 413‐423.

Abstract C173: Negative selection of ligand-receptor interactions mediating lymphocyte infiltration confers melanoma resistance to Immune Checkpoint Blockade therapy by turning hot tumors to cold

Abstract Immune checkpoint blockade (ICB) is a promising cancer therapy; however, response rates remain less than desired (less than ~40%) and resistance often develops. To learn more about ICB resistance mechanisms, we developed IRIS (Immunotherapy Resistance cell-cell Interaction Scanner), a machine learning method aimed at identifying candidate ligand-receptor interactions (LRI) that are likely to underlie ICB resistance in the tumor microenvironment (TME). Our approach considers two key components that such interactions should fulfill: they should be (1) differentially activated between the pre-treatment and post-treatment non-responderpatients, and (2) they should be predictive of ICB response in pre-treatment patients. We trained the model on the five largest publicly available melanoma bulk transcriptomics ICB cohorts and demonstrated its superior performance versus two states-of-the-art transcriptomics-based prediction methods (IMPRES and TIDE) in predicting ICB therapy response both in terms of RECIST criteria and patient survival. We further validated our identified resistance relevant LRIs in a melanoma single cell ICB cohort. Strikingly, LRIs highly activated in the pre-treatment group showed stronger predictive power for ICB response compared to the post-treatment non-responder group, which implies a potential negative selection of LRIs by tumors. Notably, many of these LRIs are mediating lymphocyte infiltration within the TME. Reassuringly, we further find a strong correlation between the activity of these LRIs and CD8+ T cells infiltration levels in the TME and are highly enriched in hot tumors in an independent cohort. Overall, these findings suggest that the tumor may develop resistance to ICB via inhibiting lymphocytes infiltration relevant ligand-receptor interactions, turning hot tumors to cold. Citation Format: Sahil Sahni, Kun Wang, Binbin Wang, Saugato Rahman Dhruba, Di Wu, Matthew Nagy, Eytan Ruppin. Negative selection of ligand-receptor interactions mediating lymphocyte infiltration confers melanoma resistance to Immune Checkpoint Blockade therapy by turning hot tumors to cold [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C173.

RTMS concurrent with cognitive training rewires AD brain by enhancing GM-WM functional connectivity: a preliminary study.

Repetitive transcranial magnetic stimulation (rTMS) and cognitive training for patients with Alzheimer's disease (AD) can change functional connectivity (FC) within gray matter (GM). However, the role of white matter (WM) and changes of GM-WM FC under these therapies are still unclear. To clarify this problem, we applied 40Hz rTMS over angular gyrus (AG) concurrent with cognitive training to 15 mild-moderate AD patients and analyzed the resting-state functional magnetic resonance imaging before and after treatment. Through AG-based FC analysis, corona radiata and superior longitudinal fasciculus (SLF) were identified as activated WM tracts. Compared with the GM results with AG as seed, more GM regions were found with activated WM tracts as seeds. The averaged FC, fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) of the above GM regions had stronger clinical correlations (r/P = 0.363/0.048 vs 0.299/0.108, 0.351/0.057 vs 0.267/0.153, 0.420/0.021 vs 0.408/0.025, for FC/fALFF/ReHo, respectively) and better classification performance to distinguish pre-/post-treatment groups (AUC = 0.91 vs 0.88, 0.65 vs 0.63, 0.87 vs 0.82, for FC/fALFF/ReHo, respectively). Our results indicated that rTMS concurrent with cognitive training could rewire brain network by enhancing GM-WM FC in AD, and corona radiata and SLF played an important role in this process.

Cancer-Preventive Activity of Argemone mexicana Linn Leaves and Its Effect on TNF-α and NF-κB Signalling

Skin cancer is the 5th most common cancer in Western countries with a surge in case occurrences making it a global burden on healthcare systems. The present study aims to evaluate the cancer-preventive activity of an ethanolic extract of Argemone mexicana Linn leaves (AML). The DMBA/TPA method was used to induce skin cancer in mice. Experimental animals were divided into three pretreatment groups of 100 mg/kg BW, 250 mg/kg BW, and 500 mg/kg BW of AML extract, and feeding was continued during the induction process. In the fourth group, 500 mg/kg BW AML extract treatment was started along with the cancer induction. The analyses were performed on the basis of the time period of in-tumour induction incidence, haematological parameters, histopathology and augmentation of TNF-α secretion and the NF-κB (p65 subunit) signalling pathway. The AML extract resisted and delayed tumour formation for up to 8 weeks in the 500 mg/kg BW pretreated group as compared to 4 weeks in the negative control group. The tumour burden varied in a dose-dependent manner in the different groups. On the 60th day, a significantly high burden (p &lt; 0.001) was observed in the negative control group and the 100 mg/kg BW group. The study was validated by investigating the expression of TNF-α and the p65 subunit of the NF-κB signalling pathway, which were found to be reduced significantly in a dose-dependent manner and significantly reduced (p &lt; 0.001) in the 500 mg/kg BW group as compared to negative control group. The 500 mg/kg BW pretreated group was found to have significant results in comparison to the 500 mg/kg BW post-treatment group. The study revealed the effective cancer preventive activity of Argemone mexicana Linn leaves (AML) in the mouse model and paved a pathway for molecular approaches which could be explored more in future studies.

TMIC-58. ALTERATIONS IN GLIOBLASTOMA TUMOR MICROENVIRONMENT TRANSCRIPTOME AFTER TREATMENT WITH PEMBROLIZUMAB

Abstract BACKGROUND Immune checkpoint inhibitors (CPI) have failed to show survival benefit in glioblastoma. Understanding the alterations in the tumor microenvironment after treatment with CPI is crucial for development of immunotherapy in glioblastoma. We previously reported our window-of-opportunity trial of pembrolizumab in GBM (NCT02337686). In the current study, we obtained 8 paired glioblastoma tumors pre- and post-treatment with pembrolizumab and conducted RNA sequencing analysis to understand the alterations in the tumor microenvironment transcriptome in response to pembrolizumab. Method: We conducted bulk RNA-sequencing profiling and differential gene expression analysis to compare the expression levels of patient-derived glioblastoma pre- and post-treatment with pembrolizumab, while controlling for paired information. We performed gene enrichment analysis on the differentially expressed genes. We employed the single sample mww-GST method to assess the enrichment of various immune cell types that were previously identified, across the two groups. RESULTS Our analysis revealed 294 down-regulated and 259 up-regulated genes in the post treatment samples. The gene enrichment analysis demonstrated that the up-regulated genes were enriched in pathways related to the immune system. The single sample mwwGST analysis indicated a consistent overall up-regulation of expression in immune cell infiltration. Notably, T cell-related signatures, such as CD4, CD8, and NKT exhibited significantly higher infiltration in the post-treatment group. Interestingly, gene ontology analyses showed upregulation of phagocytosis and antigen presentation gene modules in the post-treatment samples. Additionally, we found neuronal components and genes related to hyperexcitability and synaptic connectivity with an overrepresentation of AMPA and DLG4 pathways in post-treatment tissues. CONCLUSION Our data show that in addition to the anticipated infiltration of myeloid and lymphoid cell populations, checkpoint blockade can also unexpectedly influence glioma-neuron interactions, which may represent additional immunotherapy targets in GBM. Further proteomic validation of infiltration of different cell types and their interactome in pre- and post-CPI treated tissue is warranted.

The effectiveness of spiritual deep breathing techniques on adolescent distress in orphanages in Rembang Central Java

&lt;div class="WordSection1"&gt;&lt;p&gt;&lt;strong&gt;&lt;em&gt;Background: &lt;/em&gt;&lt;/strong&gt;&lt;em&gt;Adolescents who live in orphanages have various kinds of stressors such as adjustment to new environments, different backgrounds, academic stress, peer conflicts, financial problems, lack of affection, parental divorce, parents leaving family, and self-adjustment. The condition of adolescents who are unable to manage the stressors they face can make adolescents experience distress.&lt;/em&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;&lt;em&gt;Objectives: &lt;/em&gt;&lt;/strong&gt;&lt;em&gt;The study aims to analyze the effect of spiritual deep breathing teraphy on adolescents distress who lived in orphanages.&lt;/em&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;&lt;em&gt;Methods: &lt;/em&gt;&lt;/strong&gt;&lt;em&gt;This research used quasy experimental design method with pre-post test and control group design. The sample included 18 control groups and 18 treatment&lt;/em&gt;&lt;/p&gt;&lt;/div&gt;&lt;p&gt;&lt;em&gt;group. The sampling technique use simple random sampling with mild, moderate, and severe distress and aged 13-18 years. Distress was measured using GHQ-12 (General Health Questionnaire-12) questionnaire and interventions which were given for 3 days with a duration of 10 minutes for each therapy. Data were analyzed by using both univariate and bivariate analysis with 95% (α = 0.05) significancy level.&lt;/em&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;&lt;em&gt;Results: &lt;/em&gt;&lt;/strong&gt;&lt;em&gt;The result showed majority of the rspondent who experienced severe distress (38.9%) and moderate distress (33.33%) were senior high school student. Result of T- Independen Test between post treatment group and post control group showed p=0,007 (p &amp;lt; 0.05), it means that there was a difference two groups.&lt;/em&gt;&lt;/p&gt;&lt;strong&gt;&lt;em&gt;Conclusions: &lt;/em&gt;&lt;/strong&gt;&lt;em&gt;The result showed majority of the rspondent who experienced severe distress (38.9%) and moderate distress (33.33%) were senior high school student&lt;/em&gt;

Integration of RNA-Seq and Machine Learning Identifies Hub Genes for Empagliflozin Benefitable Heart Failure with Reduced Ejection Fraction.

This study aimed to analyze the hub genes of heart failure with reduced ejection fraction (HFrEF) treated with Empagliflozin using RNA sequencing (RNA-seq) and bioinformatics methods, including machine learning. From February 2021 to February 2023, nine patients with HFrEF were enrolled from our hospital's cardiovascular department. In addition to routine drug treatment, these patients received 10 mg of Empagliflozin once daily for two months. Efficacy was assessed and RNA-seq was performed on peripheral blood before and after treatment with empagliflozin. HFrEF-related hub genes were identified through bioinformatics analyses including differential gene expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, immune infiltration analysis, machine learning, immune cell correlation analysis and clinical indicator correlation analysis. The nine patients included in this study completed a two-month treatment regimen, with an average age of 62.11 ± 6.36 years. By performing bioinformatics analysis on the transcriptome from the treatment groups, 42 differentially expressed genes were identified, with six being up-regulated and 36 being down-regulated (|log2FC|>1 and adj.pvalue<0.05). Immune infiltration analysis of these genes demonstrated a significant difference in the proportion of plasma between the pre-treatment and post-treatment groups (p<0.05). Two hub genes, GTF2IP14 and MTLN, were finally identified through machine learning. Further analysis of the correlation between the hub genes and immune cells suggested a negative correlation between GTF2IP14 and naive B cells, and a positive correlation between MTLN and regulatory T cells and resting memory CD4+ T cells (p<0.05). Through RNA-seq and bioinformatics analysis, this study identified GTF2IP14 and MTLN as the hub genes of HFrEF, and their mechanisms may be related to immune inflammatory responses and various immune cells.