Significant Decrease In Levels Research Articles

Modulation of miR-205 expression using a Cheiranthus cheiri phyto-nano hybrid as a potential therapeutic agent against breast cancer.

Breast cancer is the fifth major cause of fatalities associated with cancer worldwide and in Pakistan, 34 066 female breast cancer cases were recorded in 2018. This study was designed to understand extracts of Cheiranthus cheiri (C. cheiri) and to evaluate the epigenetic modulation of microRNA expression for breast cancer therapy using a selected phyto-nanohybrid treatment. The phytochemical screening revealed the presence of potential phytochemicals and antioxidant scavenging activity in the C. cheiri extracts with a DPPH (2-diphenyl-1-picryl-hydroxyl) assay giving an IC50 value of 20.63 μg mL-1. GC-MS (gas chromatography-mass spectroscopy) analysis of the C. cheiri n-hexane extract detected 42 phytocompounds. Titanium oxide (TiO2) nanoparticles were synthesized and characterized using XRD (X-ray diffraction), SEM (scanning electron microscopy) and EDX (energy dispersive X-ray spectrometry) to confirm the synthesis of anatase (tetragonal) TiO2. The prepared nanoparticles were conjugated with the selected plant i.e., C. cheiri. The resulting phyto-nanohybrid was used for the subsequent treatment of breast cancer induced in a female rat model. The treatment groups were as follows: doxorubicin as the standard treatment, C. cheiri, TiO2 and the phyto-nano hybrid treatment. After 8 weeks of treatment, the groups induced to exhibit breast cancer (with and without treatment) and the control groups were dissected and analysed for histopathological, haematological and microRNA expression. Histopathological examination revealed chronic inflammation in the dilated ducts and tumour embolus formation, thus confirming the presence of breast cancer in the DMBA-induced female rat model. MicroRNA expression analysis showed a statistically significant decrease in levels of miR-205 in the plasma of the breast cancer rat model compared to the control (p < 0.05). After treatment with the phyto-nano hybrid, a statistically significant increase in the expression of miR-205 was observed in the rat models induced to exhibit breast cancer compared to the rat model without any treatment (p < 0.05). The downregulation of miR-205 in the plasma of the breast cancer exhibiting model, as compared to the control, and its upregulation after treatment with the selected phyto-nano hybrid indicated its diagnostic and prognostic significance. It is concluded that the phyto-nano hybrid used in this study is effective against breast cancer induced female rat model. All the results support the finding that the selected phyto-nano hybrid has great potential as a possible therapeutic agent for the treatment of breast cancer.

Methyl Paraben Affects Porcine Oocyte Maturation Through Mitochondrial Dysfunction.

Parabens are widely used in various industries, which are including chemical, pharmaceutical, food, cosmetic, and plastic processing industries. Among these, methyl paraben (MP) serves as an antimicrobial preservative in processed foods, pharmaceuticals, and cosmetics, and it is particularly detected in baby care products. Studies indicate that MP functions as an endocrine-disrupting compound with estrogenic properties, negatively affecting mitochondrial bioenergetics and antioxidant activity in testicular germ cells. However, limited information exists regarding studies on the effects of MP in oocytes. The aim of this study was to investigate the specific mechanism and the toxic effects of MP during oocyte maturation cultured in vitro using a porcine oocyte model. The results indicated that MP (50 μM) inhibited oocyte expansion, significantly reducing the expression of expansion-related genes MAPK1 and ERK1, and decreased the first polar body extrusion significantly as well. ATP levels decreased, reactive oxygen species (ROS) levels remained unchanged, and glutathione (GSH) levels decreased significantly, resulting in an elevated ROS/GSH ratio. The expression of antioxidant genes SOD1 and GPX was significantly decreased. Additionally, a significant decrease in levels of mitochondrial production and biosynthesis protein PGC1α+β, whereas levels of antioxidant-related protein Nrf2 and related gene expression were significantly increased. Autophagy protein LC3B and gene expression significantly decreased, and apoptosis assay indicated a significant increase in levels of caspase3 protein and apoptosis-related genes. These results demonstrated the negative effect of MP on oocyte maturation. In conclusion, our findings indicate that MP disrupts redox balance and induces mitochondrial dysfunction during meiosis in porcine oocytes, resulting in the inhibition of meiotic progression. The present study reveals the mechanism underlying the effects of methyl para-hydroxybenzoate on oocyte maturation.

The impact of the COVID-19 pandemic on the dispensing of systemic anti-cancer therapy (SACT) in Ireland: A population based study

ObjectivesThe COVID-19 pandemic had considerable implications for cancer related care. This study aimed to examine its impact on the dispensing of systemic anti-cancer therapy (SACT) in Ireland. Study designA repeated cross-sectional design was used which involved a quasi-experimental interrupted time series analysis (ITSA), and autoregressive integrated moving average (ARIMA) models. MethodsThis nationally representative study utilised monthly pharmacy claims (i.e. dispensing) data from community and hospital schemes. Dispensed items among individuals prescribed any SACT from January 2019 to April 2021 were included. ResultsDuring the study period, 641,273 SACT items were dispensed, including 57,199 chemotherapeutic agents (8.9 %), 15,970 immunotherapeutic agents (2.5 %), 87,813 targeted therapies (13.7 %), and 480,291 (74.9 %) endocrine therapies. There were on average 3.3 and 4.1 fewer immunotherapy and targeted therapy agents, respectively, dispensed per 100,000 population per month post-March 2020 (vs. expected), compared to the level prior to March 2020. For endocrine therapy, there was a significant slowing of the trend post-March 2020 compared to the pre-pandemic period (slope change = −1.72, 95 % CI -2.9 to −0.5; p<0.01). ConclusionThere was a significant level decrease in the dispensing of immunotherapy and targeted therapy during the first year of the pandemic, and a slowing of the trend for endocrine therapies. However, no differences in the dispensing of other SACT were observed.

Acupoint Autohemotherapy Alleviates Airway Inflammation in Asthmatic Rats via Upregulating Expression of Hemeoxygenase-1.

Acupoint autohemotherapy (AA), a therapeutic technique involving the subcutaneous injection of autologous blood into acupoints, has been empirically validated as safe and effective for treating asthma by alleviating symptoms and decreasing acute attacks, though its mechanism is not well understood. The role of heme oxygenase-1 (HO-1) in AA-induced suppression of asthmatic airway inflammation is examined. Twenty rats were assigned randomly to four groups, namely the Control, OVA, OVA + AA, and (OVA + Snpp) + AA. Rats in the OVA + AA and (OVA + Snpp) + AA received autologous blood injections into acupoints (BL13 and BL23) following OVA challenge. Rats in the (OVA + Snpp) + AA were concurrently subjected to intraperitoneal injections of Snpp, a inhibitor of HO-1. Airway inflammation was evaluated through HE staining, while the concentrations of cytokines in BALF were quantified using ELISA. The mRNA and protein levels of RORγt (Th17-specific transcription factor), Foxp3 (Treg-specific transcription factor), and HO-1 in lung tissue were assessed through qRT-PCR and WB. HE staining indicated that airway inflammation was alleviated in the OVA + AA. The OVA + AA displayed significantly lower counts of total cells and eosinophils in the BALF compared to both the OVA and (OVA + Snpp) + AA. The ELISA demonstrated a significant decrease in levels of pro-inflamatory cytokines (IL-4, IL-17A), and an increase in levels of anti-inflamatory cytokines (IFN-γ, IL-10), in the OVA + AA when compared to both OVA and (OVA + Snpp) + AA. The qRT-PCR and WB analyses revealed an upregulation of HO-1 and Foxp3 expression, and a downregulation of RORγt expression, in the OVA + AA when compared to OVA and (OVA + Snpp) + AA. The involvement of HO-1 in the underlying mechanism responsible for the anti-inflammatory effects of AA is evident.

Evaluation of Adipose Tissue Hormones and Tumor Necrosis factor in Patients with Endometriosis

Objective: To evaluate levels of physiological parameters (Testosterone, follicle stimulating hormone FSH, luteinizing hormone LH, leptin and tumor necrosis factor TNF-α, Adipsin and Ghrelin), Total antioxidant capacity-TAC, Glutathione S transfers -GST in sera of patients with endometriosis. Method: This study involved (85) women within reproductive age (25-40) years, who were distributed into two groups: patientsʹ group (55) women diagnosed with endometriosis, and (30) healthy control women. The study was carried out at Al-Karkh Maternity Hospital/ Baghdad and extended from 20/4/2024 to 20/5/2024. The pathological cases of patients were diagnosed by clinical examinations and confirmed by specialist physician with ultrasound examination. Blood samples were taken from both groups, serum was separated for each individual by a centrifuge. Results: a significant rise in the (FSH, Leptin, TNF -α, Adipisin) while a significant decrease in levels of (Testosterone , LH, GST, TAC, Ghrelin) concentration were found in the sera of patients compered to healthy women , with a probability of P ≤ 0.05. According to Receiver operating characteristic (ROC) statistical analysis, Area under curve (AUC ) for LH, leptin, TNF -α, adipsin, ghrelin, GST, TAC were closely or equal to (1) for patients . Conclusion: serum levels of LH, Leptin, Adipisin, Gherlin, TNF-α and GST can be dependable as prognostic indicator markers that reflect the degree of oxidative stress accompanying endometriosis.

Down regulation of the c-Fos/MAP kinase signaling pathway during learning memory processes coincides with low GnRH levels in aluminum chloride-induced Alzheimer's male rats.

Aluminum chloride (Al) is associated with Alzheimer's disease (AD) and reproductive disorders. But the relationship between gonadotropin-releasing hormone (GnRH) and c-Fos levels, the end product of MAP-kinase signaling, in AD is unknown, so we aimed to investigate this relationship. We exposed rats to Al dissolved in drinking water (10 and 50mg/kg) for two and four weeks. The control group received only drinking water. At the end, the blood sample was collected under deep anesthesia and the brain was dissected on ice, and the testicular tissue was fixed in formalin. Amyloid beta (βA) plaques in brain regions and the number of CA1 neurons were evaluated by Congo red staining and cresyl violet staining. Activation of neuronal nitric oxide synthase (nNOS) was studied using NADPH-diaphorase. The levels of c-Fos and testosterone receptors in the target area were examined immunohistochemically. Brain GnRH levels were determined by blotting, and serum levels of gonadotropins and steroids were measured by enzyme-linked immunosorbent assay (ELISA). All data were analyzed using analysis of variance (ANOVA) at α = 0.05 level. The accumulation of βA plaque was observed along with a decrease in the number of CA1 pyramidal neurons and a significant decrease in the levels of c-Fos and GnRH in the brains of rats receiving Al, which was aligned with a significant decrease in serum levels of testosterone and LH. This study, for the first time, showed a link between dementia and a concomitant decrease in brain GnRH and c-Fos levels.

Effect of orange pulp with or without zeolite on productive performance, nitrogen utilization, and antioxidative status of growing rabbits

The current study was designed to investigate the effect of dried orange pulp inclusion (OP diet), natural zeolite addition (Z diet), or both (OPZ diet) compared to control (CON diet) on digestibility, growth performance, nitrogen utilization, blood biochemical, antioxidative status, and cecum microbiota of growing rabbits. Seventy-two V-line male rabbits (6 weeks old) were divided into 4 balanced experimental groups. Results showed that administration of dried orange pulp or zeolite especially the OPZ diet significantly improved nutrient digestibility and nutritive values. Rabbits fed the experimental diets (OP, Z, or OPZ) recorded significantly higher values of average daily gain, N-retention, and N-balance compared with those fed the CON diet. Data on blood biochemical, showed non-significant differences in globulin concentrations, and significant decreases in levels of cholesterol, LDL (low-density lipoproteins), triglycerides, and MDA (malondialdehyde) as an antioxidant biomarker with OP, Z, or OPZ diets. Moreover, the incorporation of orange pulp or zeolite in diets significantly decreased the cecal count of E. coli, with no significant difference in total bacterial count among the experimental groups. It could be concluded that a combination between dried orange pulp and natural zeolite in the diet can enhance the growth performance, antioxidant and health status of rabbits.

Anti-tumor property of Argemone mexicana leaves methanol extracts against 7, 12- Dimethylbenz[a]anthracene (DMBA) induced mammary tumors in experimental rats

Background: Breast cancer is a complex and multistage process. Many natural compounds are available for an effective and efficient alternative method against breast cancer. This study focused on the anti-cancer activity of Argemone mexicana leaf extract on Dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in experimental rats. Materials and Methods: Argemone mexicana Leaves (AML) were collected, extracted by soxhlet apparatus with methanol solvent, and analyzed by Gas Chromatography and Mass-Spectroscopy (GCMS). Healthy Female Sprague-Dawley rats (7-8 weeks and 100 ± 20 g) were divided in five groups and used to induce mammary tumors by DMBA [25 mg/kg/ Subcutaneous (s.c.)]. After developing a palpable nodule (10-12 weeks after DMBA), the rats were treated with AML extract [200 and 400 mg/kg/Body Weight (b.w.)] and Tamoxifen (TAM 10 mg/kg) orally for 12 weeks. Body weight, tumor weight and volume measurements, lipid peroxidation, antioxidant and tumor marker [Carcinoembryonic Antigen (CEA)] levels, and histological investigations were assessed. Results: Following AML treatment, there was a reduction in weight and volume (P&lt; 0.01) of breast tumor, as well as a significant decrease in levels of lipid peroxidation and tumor marker CEA (P &lt; 0.001) and improved Superoxide Dismutase (SOD), Reduced glutathione (GSH), and caspase levels (P &lt; 0.001). In cytological results, AML improved the cellular architecture, and significant restoration in histopathological examinations revealed a tumor with minimal glandular epithelium proliferation, a decrease in mitotic figures, and nuclear alterations. Conclusion: The study suggests that AML extract has a chemoprotective effect against DMBA-induced mammary tumors in experimental animals, specifying its possibility as a therapeutic agent for breast cancer treatment.

Severe carbohydrate restriction augments the antiproliferative effect of hormonal therapy in a murine model of Ehrlich breast adenocarcinoma: histological and immunohistochemical investigations

BackgroundMalignant tumors of the breast are the most diagnosed cancers in females globally. Recent evidence suggests that carbohydrate restriction (CR), especially ketogenic diets, has become a potential treatment approach for many malignancies, including breast cancer. Tamoxifen (TAX) is a selective estrogen receptor modulator (ERM) that can reduce the risk of cancer recurrence. The current work was designed to assess the impact of CR on the proliferation of breast adenocarcinoma cells and to compare this impact with that of TAX. Study groups included: group 1: vehicle-treated mice; group 2: the Ehrlich group: injected Ehrlich ascites carcinoma (EAC) cells (2.5 × 106) in 0.25 ml isotonic saline; group 3: CR group: mice were supplied with a diet regimen of severe CR throughout the study and injected EAC at week 7; group 4: hormonal therapy (HT) group: mice in this group injected with EAC at week 7 and then received TAX at a dose of 20 mg/kg 3 times/week orally for 3 weeks; and lastly group 5: the group of combined intervention. The mice in the CR, HT, and the combined groups received Ehrlich cancer cells at the same dose and route as the Ehrlich group.ResultsCR and HT groups demonstrated a significant decrease in levels of insulin-like growth factor (IGF-1), carbohydrate antigen (CA 15–3), hexokinase 2 (HK2), hypoxia-inducible factor-1 (HIF-1) α, and malondialdehyde (MDA) compared to the Ehrlich group. Additionally, the mean area % of caspase-3 was significantly increased, and the mean area % of Ki67 and estrogen receptor (ER)α was significantly decreased.ConclusionsThe combined treatment demonstrated the most advantageous outcome, as evidenced by reduced CA 15–3 levels, tumor size, and the mean area % of Ki67. This suggests that the addition of severe CR to the conventional therapy of breast cancer has a beneficial effect.

P118 EFFECT OF A FIXED COMBINATION THERAPY WITH PERINDOPRIL/AMLODIPINE AND ROSUVASTATIN TO PATIENTS WITH HIGH AND VERY HIGH RISK HYPERTENSION AND DYSLIPEDEMIA

Purpose: Assess achievement target level blood pressure, LDL cholesterol, non-HDL cholesterol, Triglyceride, patients with high, very high risk AH during 6-month therapy with fixed combination perindopril/amlodipine addition rosuvastatin. Material, methods: Study included 43 patients hypertension I-II degrees (ESC/ESH, 2018), All patients assessed for cardiovascular risk using the SCORE2scale, high risk identified n=34 (80%) patients, very high n=9 (20%) patients. Average age patients 58.23±9.82 years, the average duration hypertension 13.07±8.53 years. SBP 159.46±10.52 mmHg, DBP 91.69±8.60 mmHg. All patients underwent: determination level blood lipids, glucose, ALT, AST, CPK, creatinine, uric acid in the blood and microalbuminuria. All patients with AHT and hypolipidemic purposes prescribed fixed combination drug perindopril/amlodipine and rosuvastatin. Drug dose titrated every 2 weeks until target values of BP and LDL cholesterol (&lt;100-70 mg/dl), non-HDL cholesterol (&lt;100-85 mg/dl), TG (&lt;150 mg/dl) achieved. Average drug doses were perindopril at dose 4 to 8 mg/day, amlodipine dose 5 to 10 mg/day, initial dose orosuvastatin10 mg/day. All types analysis, p values &lt;0.05 were considered statistically significant (Wilcoxontest). Results: In general, 6-month combination therapy with perindopril/amlodipine, rosuvastatin showed high lipotensive effectiveness. There was significant decrease in scores SCORE2scale, LDL cholesterol, non-HDL cholesterol, TG, SBP, DBP, blood pressure. The degree of scores SCORE2scale: initially 20.92±8.05 dynamics 14.92±9.66 points (p&lt;0.001); LDL cholesterol 146.53±35.90,dynamics 114.86±36.43 mg/dl (p&lt;0.003); Non-HDL cholesterol 185.61±35.90 mg/dl, dynamics 143.25±37.01 mg/dl (p&lt;0.079); TG 181.23±108.47 dynamics 143.90±64.47 mg/dl (p&lt;0.006); SBP 159.84±9 mmHg, dynamics 131.65±5.93 mmHg (p&lt;0.000); DBP 91.69±8.60 mmHg, dynamics 82.55±4.17 mmHg(p&lt;0.000); BPmean 115.48±7.22 mmHg, dynamics 99.96±3.75 mmHg. (p&lt;0.000). In addition SBP decreased by -16.86±4.70%, DBP by -8.16±6.99%. The target level LDL cholesterol reached by39% patients, non-HDL cholesterol by 18%, Triglycerides by 55%, the target level SBP reached 88%, DBP 81% patients, SBP and DBP simultaneously 81% patients. Conclusion: Analysis effectiveness of combination therapy with drug perindopril/amlodipine, rosuvastatin showed significant decrease in level of indicators SCORE2 scores, LDL cholesterol, non-HDL cholesterol, TG, SBP, DBP, blood pressure. In patients with high, very high risk hypertension.

Role of Quercetin Supplementation on Iron Parameters in Blood Transfusion-Dependent Thalassemia Patients

Background: Thalassemia is a group of inherited blood disorders that affect the production of hemoglobin, a protein in red blood cells that carries oxygen throughout the body. Iron overload is a condition in which the body absorbs and stores too much iron. In addition to repeated blood transfusions, increased gastrointestinal tract (GIT) iron absorption plays an important role in iron overload with thalassemia. Quercetin, a common flavonoid present in fruits and vegetables, exhibits diverse biological effects. Objective: To assess the effect of quercetin on iron overload parameters in blood transfusion-dependent thalassemia patients (TDT). Methods: A randomized, double-blind, placebo-placebo group-led study was conducted on 110 TDT patients, more than 12 years of age, who were supplemented with either quercetin or a placebo capsule daily (500 mg) for 3 months. A blood sample was obtained for laboratory parameters at baseline and at the end of 3 months. Results: At the baseline time of the study, the demographic features and iron overload parameters of patients and the placebo group were not statistically different, while after three months of supplementation, there was a significant decrease in levels of serum iron, UIBC, serum ferritin and ferritin saturation rate, and a significant increase in TIBC in the patients compared with the placebo group. Conclusions: The study shows the significant role of quercetin on iron overload parameters in blood transfusion-dependent thalassemia patients.

Study of the Effect of Fresh Green Asparagus officinalis L. Stems Extract and Metformin Drug on Induced Polycystic Ovary Syndrome (PCOS) in Female Albino Rats

During this research, Polycystic Ovary Syndrome (PCOS) was studied and the effect of Metformin Drug and an extract of fresh Asparagus officinalis L. stems on it was studied. The study involved 20 adult female albino rats divided into four groups, each containing five female rats. The first group received a physiological saline solution, while the second group was induced with Polycystic Ovary Syndrome (PCOS) by being dosed with Letrozole. The third group, after the induction of PCOS, was treated with Metformin, and the fourth group was dosed with Fresh Asparagus officinalis L. stems extract. The study focused on hormonal and Histological changes. The results showed that the group of rats with PCOS induced by Letrozole had a significant decrease in the levels of Progesterone (Prog.) and Oestradiol (E2) hormones, and a significant increase in Testosterone (Testo.) compared to the control group. Dosing rats with Fresh Asparagus officinalis L. stems extract led to a significant decrease in (E2) hormone level and a significant increase in Progesterone (Prog.) hormone level compared with the control group. Dosing rats with Metformin led to a significant decrease in (E2) hormone level and a significant increase in Progesterone (Prog.) and Testosterone (Testo.) hormone levels compared to the control group. The results also indicated significant changes in hormone levels between Treatment groups and PCOS induction group. The histological study revealed changes in the shape of the ovary, the appearance of cystic structures, congestion of blood vessels, and increased ovarian cellularity. Metformin showed fewer Histological changes, while Asparagus officinalis L. stems extract had a therapeutic effect with moderate severity, leading to the disappearance of cystic vesicles and the appearance of corpus luteum and primary vesicles. In conclusion, we conclude that both the therapeutic agents Metformin and the extract of Fresh Asparagus officinalis L. stems showed a therapeutic effect on Polycystic Ovary Syndrome, as Metformin drug showed a treatment for this Syndrome, but it requires a long period to show this result, meaning we need more than 28 days, which is the duration of the study, but Asparagus officinalis L. stems extract had Faster healing effect within just 28 days. Fresh Green, tender Asparagus officinalis L. stems is one of the significant medicinal plants that is used to treat or prevent polycystic ovarian syndrome. Research has shown that it is an effective treatment for the condition. Future researchers studying polycystic ovarian syndrome will find this article useful.

Comparison of matrix metalloproteinase levels in periodontal pockets treated with chlorhexidine and propolis

Natural antimicrobial products are attracting interest in the treatment of periodontal diseases due to their minimal or nonexistent side effects. Propolis, a complex resin content produced by bees, has drawn particular interest for its antibacterial effects, including inhibitory effects on periodontopathogenic bacterial species. This study compared the effects of propolis, a natural product, and chlorhexidine, the gold standard antimicrobial agent, on MMP-1 and MMP-9 levels in gingival crevicular fluid (GCF). Subgingival irrigations of chlorhexidine and propolis solutions were performed in selected deep periodontal pockets of periodontitis patients along with scaling and root planing. The treatment protocol was administered three times at one-month intervals starting from the initial day of the study. GCF MMP-1 and MMP-9 levels, along with clinical periodontal parameters, were evaluated before and after treatment. The study results showed that a statistically significant decrease in clinical periodontal parameters in both groups (p&amp;lt;0.001). Biochemical analysis revealed a statistically significant decrease in levels of GCF MMP-1 and MMP-9 in both groups (p&amp;lt;0.005). Additionally, the decrease in GCF MMP-1 levels was found to be significantly greater in the propolis group compared to the chlorhexidine group (p&amp;lt;0.001).

THE EFFECTIVENESS OF COGNITIVE-BEHAVIORAL THERAPY IN ADOLESCENTS WITH SOCIAL ANXIETY DISORDER

Social anxiety disorder (SAD) is a prevalent condition among adolescents, characterized by an intense and persistent fear of social situations or performance, which results in significant distress and impairment in daily activities. Adolescents with SAD often avoid social interactions, which can negatively affect their academic, social and emotional development. Cognitive-behavioral therapy (CBT) has been widely recognized as an effective approach to treating SAD, offering practical strategies to reduce anxiety symptoms and improve social functioning. This abstract will explore the effectiveness of CBT in adolescents with social anxiety disorder, highlighting the main techniques used and the clinical outcomes observed. The aim of this paper is to review and evaluate the effectiveness of cognitive-behavioral therapy in the treatment of adolescents with social anxiety disorder. The aim is to analyze the main techniques of CBT, the mechanisms by which it promotes anxiety reduction and the results of clinical studies that show its effectiveness. In addition, the challenges and specific considerations in applying CBT to this age group will be discussed. This literature review aims to analyze the effectiveness of Cognitive-Behavioral Therapy (CBT) in the treatment of social anxiety in adolescents. To this end, references from relevant studies and meta-analyses were selected and reviewed, covering various approaches and results related to the topic. The selection of references was based on the relevance and impact of the publications in the field of psychotherapy and social anxiety. CBT is a form of psychotherapy based on identifying and modifying dysfunctional patterns of thought and behavior. In the context of SAD in adolescents, CBT aims to help patients recognize and restructure irrational beliefs about themselves and social situations, develop appropriate social skills and reduce avoidance of social interactions. With this in mind, the main CBT techniques include cognitive restructuring, gradual exposure and social skills training. Cognitive restructuring involves helping adolescents to identify negative automatic thoughts and replace them with more realistic and balanced interpretations. Gradual exposure consists of exposing adolescents, in a controlled and progressive way, to feared social situations, allowing them to face their fears and reduce the associated anxiety response. Social skills training focuses on developing social competencies, such as initiating and maintaining conversations, asking and answering questions, and dealing with criticism and rejection in an assertive manner. Clinical studies have demonstrated the effectiveness of CBT in reducing SAD symptoms in adolescents. Research indicates that adolescents who receive CBT show a significant decrease in levels of social anxiety, improved quality of life and greater participation in social and school activities. For example, a study conducted by Masia Warner et al. (2005) showed that adolescents who participated in a group CBT program had a notable reduction in social anxiety symptoms compared to a control group. Another study by Beidel, Turner and Morris (2000) showed that individual CBT resulted in substantial improvements in adolescents’ social anxiety and social functioning. Despite the promising results, the application of CBT to adolescents with SAD presents specific challenges. Adherence to treatment can be hampered by adolescents’ resistance to engaging in therapy sessions and facing feared social situations. In addition, parental involvement and coordination with schools are important components for successful treatment, as social and environmental support is crucial for the generalization of therapeutic gains. Therefore, cognitive-behavioral therapy has proven to be an effective approach for treating adolescents with social anxiety disorder. Cognitive restructuring techniques, gradual exposure and social skills training are key to helping adolescents overcome their fears and improve their social functioning. Clinical studies provide robust evidence that CBT can significantly reduce SAD symptoms and improve quality of life for adolescents. However, it is essential to consider the challenges specific to this age group, including resistance to treatment and the need for support from parents and schools. With a careful and collaborative approach, CBT can provide lasting benefits for adolescents with social anxiety disorder, promoting their emotional and social well-being.

Histopathological Changes and Metallothionein Levels in Filopaludina javanica During Depuration

The heavy metal lead has been reported to pollute waters along the Glagah River, Lamongan Regency, Indonesia. Lead contamination in all organs of the Tutut snail (Filopaludina javanica) was detected at 2.92 ± 0.5 ppm. Therefore, lead contamination can cause severe problems because lead can accidentally accumulate in the human body through the food chain. One effort to reduce risks related to food safety is Depuration. The research aimed to analyze the effect of Depuration using a flushing system on histopathological changes and metallothionein levels in all organs of the spotted snail (Filopaludina javanica). The research used a Completely Randomized Design with four treatments and three replications. Treatment includes flushing time (6 hours, 12 hours, 18 and 24 hours). The MT response was tested statistically using One Way Anova, while the histopathological analysis used a descriptive method by comparing before treatment and after flushing treatment for 24 hours, to determine metallothionein levels, the ELISA (Enzyme-Linked Immunosorbent Assay) method was used. The results showed tissue damage in edema, hyperplasia, and vacuolation. Tissue damage before and after Depuration was relatively the same and included in the low category, with damage ranging from (0-6.1%). Meanwhile, metallothionein analysis has not shown a significant decrease in levels. Metallothionein levels increased with the duration of flushing. Further checks showed that the media water used in flushing during Depuration contained Fe and Zn, which resulted in increased MT levels

Prognostic Value of Pentraxin 3 and Procalcitonin in Late onset Neonatal Sepsis

Abstract Background Sepsis is a major cause of intensive care unit (ICU) admission. Procalcitonin (PCT) could be an important prognostic marker for sepsis. Pentraxin 3 (PTX3) and PCT are detectable in patients with sepsis within a large time window after the onset of sepsis. Objective To assess the prognostic value of the PTX3, PCT in neonatal sepsis in comparison with other sepsis screen. Patients and Methods A prospective study included 40 neonates with sepsis. The study had been conducted in the neonatal intensive care units of Ain Shams University, Children’s Hospital during the period from January 2020 to May 2022. All neonates had been subjected to clinical examination, anthropometric measurements and sepsis scoring by neonatal sequential organ failure assessment (nSOFA). Laboratory investigations were collected from all pediatrics including Complete blood count (CBC), quantitative C- reactive protein (CRP), blood culture, serum pentraxin 3 (PTX3) and serum procalcitonin (PCT). Sepsis markers had been obtained from neonates at the day of being with suspected sepsis before starting the antimicrobial therapy (Day 0). While blood samples for sepsis markers reobtained only from neonates with positive blood cultures on the 3rd (Day3), accordingly our patients divided into improved and deteriorated groups. Results There was a significant decrease in CRP level and increase in procalcitonin and pentraxin 3 levels in deteriorated group than improved group at baseline with p-value = 0.004, 0.016 and 0.019; respectively. Also, the study shows that there was a significant increase in CRP, procalcitonin and pentraxin 3 levels in deteriorated group than improved group after 3 days with p-value = 0.002, &amp;lt;0.001 and &amp;lt;0.001; respectively. Furthermore, in improved group, there was a significant decrease in the level of CRP, procalcitonin and pentraxin 3 after 3 days than at baseline with p-value = 0.001, &amp;lt;0.001 and 0.001; respectively. Also in deteriorated group, there was statistically significant increase in the CRP and pentraxin 3 levels after 3 days than at baseline in deteriorated group with p- value = 0.002 and 0.019; respectively while no change found in procalcitonin level. Conclusion Serum pentraxin 3 and procalcitonin levels seem to be promising prognostic markers in neonatal sepsis with higher sensitivity and specificity for procalcitonin than pentraxin at 3 days.

Peripheral-central network analysis of cancer cachexia status accompanied by the polarization of hypothalamic microglia with low expression of inhibitory immune checkpoint receptors

While the excessive inflammation in cancer cachexia is well-known to be induced by the overproduction of inflammatory mediators in the periphery, microflora disruption and brain dysfunction are also considered to contribute to the induction of cancer cachexia. Hypothalamic microglia play a crucial role in brain inflammation and central-peripheral immune circuits via the production of inflammatory mediators. In the present study, we evaluated possible changes in excessive secretion of gut microbiota-derived endotoxin and the expression timeline of several inflammation-regulatory mediators and their inhibiting modulators in hypothalamic microglia of a mouse model of cancer cachexia following transplantation of pancreatic cancer cells. We demonstrated that the plasma level of lipopolysaccharide (LPS) was significantly increased with an increase in anaerobic bacteria, especially Firmicutes, in the gut at the late stage of tumor-bearing mice that exhibited dramatic appetite loss, sarcopenia and severe peripheral immune suppression. At the early stage, in which tumor-bearing mice had not yet displayed “cachexia symptoms”, the mRNA expression of pro-inflammatory cytokines, but not of the neurodegenerative and severe inflammatory modulator lipocalin-2 (LCN2), was significantly increased, whereas at the late “cachexia stage”, the level of LCN2 mRNA was significantly increased along with significant decreases in levels of inhibitory immune checkpoint receptors programmed death receptor-1 (PD-1) and CD112R in hypothalamic microglia. In addition, a high density of activated neurons in the paraventricular nucleus (PVN) of the hypothalamus region and a significant increase in corticosterone secretion were found in cachexia model mice. Related to the cachexia state, released corticosterone was clearly increased in normal mice with specific activation of PVN neurons. A marked decrease in the natural killer cell population was also observed in the spleen of mice with robust activation of PVN neurons as well as mice with cancer cachexia. On the other hand, in vivo administration of LPS in normal mice induced hypothalamic microglia with low expression of inhibitory immune checkpoint receptors. These findings suggest that the induction of cancer cachexia may parallel exacerbation of the hypothalamic inflammatory status with polarization to microglia expressed with low levels of inhibitory immune checkpoint receptors following LPS release from the gut microflora.

Acceleration of Wound Healing in Diabetic Rats through a Novel 3D Organo-Hydrogel Nanocomposite of Polydopamine/TiO2 Nanoparticles and Cu (PDA-TiO2@Cu).

Diabetic wound represents a serious issue with a substantial impact and an exceptionally complex pathology affecting patients' mental health and quality of life. So, we have developed a novel 3D organo-hydrogel nanocomposite of polydopamine/TiO2 nanoparticles and cu (PDA-TiO2@Cu) and examined its efficacy in diabetic wound healing. Forty-five adult male albino rats were divided into normal control rats (non-diabetic rats with non-treated skin wounds), diabetic control rats (diabetic rats with non-treated skin wounds), and organo-hydrogel-treated rats (diabetic wounds treated with topically applied organo- hydrogel once daily). Macroscopic changes of the wound were observed on days 0, 3, 5, 7, and 10 to measure wound diameters. Skin specimens from the wound tissue were taken on days 3, 7, and 10, respectively, and examined histologically and immunohistochemically. Also, the gene expressions of collagen I, Matrix Metalloproteinase-9 (MMP-9), and Epidermal Growth Factor (EGF), and levels of Interleukin 6 (IL-6) and Superoxide Dismutase (SOD) were assessed. Our observed results indicated that the developed patch significantly accelerated the healing time compared to the normal control and diabetic control groups. Moreover, the patchloaded group revealed complete re-epithelization and a highly significant increase in the mean area % of CD31 immunostaining on day 7. The organo-hydrogel-loaded group displayed a significant decrease in gene expression of MMP-9 and a significant increase in gene expression of EGF and collagen I. Additionally, the organo-hydrogel-loaded group exhibited a significant decrease in levels of IL-6 and a significant increase in levels of SOD, compared to the normal diabetic control groups. The organo-hydrogel can be used for treating and decreasing the healing period of diabetic wounds.

A cross talk study on sitagliptin mediated reclamation on TGF β signalling, DPP 4, miR-29a and miR-24 expression in PCOS rats fed with high fat-high fructose diet

Polycystic Ovary Syndrome (PCOS) is a multifactorial reproductive, endocrine and metabolic disturbance which is very commonly observed in females of reproductive age group. The disease is still incurable however the use of synthetic drugs in combination with lifestyle is recommended. Accordingly, the present study was conducted to investigate the possible beneficial effects of sitagliptin on PCOS induced rats on control diet (CD)/high fat- high fructose diet (HFFD). PCOS was induced by giving testosterone propionate (TP) for 28 days to both the CD/HFFD rats and treated with STG i.p. for last 15 days. At the end of the experiment lipid profile, inflammatory markers, expression of NF-κB-p65, miR-24 and miR-29a, fibrotic and apoptotic proteins from ovary tissue were examined. Moreover, lipid accumulation and fibrosis of ovary tissue was further confirmed using Sudan III and Masson’s trichrome stain. STG treated rats exerted a significant decrease in levels of cholesterol, TG, LDL-C, VLDL-C, IL-6 and TNF-α and increased HDL-C level, miR-24 and miR-29a expression. STG treated groups expressed significantly decreased expression of NF-κB-p65, TGF-β1, p-Smad 2 and p-Smad 3 followed by no significant changes in the expression of BAX, caspase-9, caspase-3 and Bcl-2 in all the PCOS induced groups. Among all the CD/ HFFD fed groups, rats on HFFD showed more devastating effect which suggests that diet plays a major role in genesis of PCOS. In conclusion, current results reflect the potential impact of STG against dyslipidaemia, inflammation and fibrosis in PCOS rats via regulating dyslipidaemia and fibrosis via DPP 4 mediated miR-29a expression.

The Effect of Infection with some Intestinal Parasites on some Immune Parameters

275 fecal samples were collected from visitors to Tikrit Teaching Hospital and some private laboratories in Tikrit city/Salah al-Din Governorate. The collection period lasted from December 2022 until April 2023. The study included examining samples of both males and females of different ages. The study showed a significant decrease in level of IgG among people infected with Entamoeba histolytica by 92.00 ± 19.1, as well as for people infected with Giardia lamblia, as a significant decrease was recorded by 76.43 ± 15.1 compared to healthy people by a percentage of 130.60 ± 29.5. No significant difference was recorded between people infected with E.histolytica in level of IgM, as the percentage reached 83.4 ± 13.6. Likewise, for people infected with G.lamblia, no significant difference was recorded, as the percentage was (106.0 ± 21.7) compared to healthy people, as the percentage reached ( 84.6 ± 18.0. ). There was a significant decrease in the level of the CD4 differentiation complex among people infected with E. histolytica by a rate of 160.8 ± 23.9. Likewise, for people infected with G. lamblia, a significant decrease was recorded, reaching a rate of 187.5 ± 31.8 compared to healthy people by a rate of 475.2 ± 28.1. A significant decrease was recorded among people infected with E. histolytica in the level of CD8 differentiation complex, as the percentage reached 9.00 ± 2.51. Likewise, for people infected with G. lamblia , a significant decrease was recorded by 10.18 ± 2.60 compared to healthy people, with a percentage of 14.50 ± 3.40. There was a significant decrease in the level of IL6 in people infected with E. histolytica, as the percentage reached 85.02 ± 13.20, while in people infected with G. lamblia, no significant difference was recorded, as the percentage reached 196.30 ± 17.10, compared to healthy people, with a percentage of 220.20 ± 23.20.