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Assessment of Antidepressant Activity of Stem of Jasminum multiflorum Andrews and Jasminum mesnyi Hance by Modulating Neurochemicals and Reducing Oxidative Stress
No full textBackground: Depression is a prominent psychiatric condition that needs efficient management through various therapeutic approaches. The genus Jasminum has a diverse array of attractive shrubs that are classified under the Oleaceae family and distributed throughout India. Jasmine plants have been extensively employed in the fragrance business to produce fragrances, oils, and lotions. Moreover, these substances have been conventionally employed in managing wounds, cancer, inflammation, urolithiasis, cardiac disease, stress, rheumatism, and other medical conditions. The present study assessed the possible antidepressant properties of two plant species, namely Jasminum multiflorum (J. multiflorum) Andrews and Jasminum mesnyi (J. mesnyi) Hance, members of the Oleaceae family. Methods: The stems of J. multiflorum and J. mesnyi were subjected to successive extraction methods involving petroleum ether, chloroform, ethanol, and water. The initial inquiries into the quality of the medicine led to the assessment of the antidepressant properties of each subsequent extract. This evaluation was conducted on Swiss albino mice using the Force swim test and Tail suspension test, with four different doses administered orally (150, 300, 450, and 600 mg/kg body weight). The present study evaluated and assessed two distinct extracts, namely the ethanolic extract and the aqueous extract, obtained from each plant. The objective was to investigate and analyse their potential antidepressant action. This was accomplished by utilising two specific tests conducted on mice: the 5-hydroxy tryptamine-induced head twitches test and the tetrabenazine antagonism test. The potential antidepressant effects of each species most active ethanolic extract were evaluated using the chronic unpredicted mild stress method. Following the chronic unpredictable mild stress test, biochemical parameters (including Malondialdehyde, Superoxide dismutase, Catalase, and Reduced glutathione) were assessed in both species. Results: The findings from the inquiry indicate that the administration of an ethanolic extract derived from J. mesnyi and J. multiflorum demonstrates a positive effect on the modified behaviour observed in mice. Specifically, it (p < 0.05, p < 0.01, p < 0.001) reduces head twitching in the 5-hydroxy tryptamine-produced Head twitch test and alleviates symptoms of ptosis and catalepsy in depressed mice through tetrabenazine antagonism. The group treated with the ethanolic extract of J. mesnyi and J. multiflorum exhibited (p < 0.01, p < 0.001) decrease in immobility time compared to the negative control group. Furthermore, the administration of an ethanolic extract derived from J. mesnyi has been shown to improve (p < 0.01, p < 0.001) the disrupted oxidative stress levels in the brain tissue of mice suffering from depression generated by persistent unpredicted mild stress. Conclusion: The studys findings indicate that the administration of ethanolic extract derived from J. mesnyi and J. multiflorum positively affects the behavioral alterations and neurochemical balance in a mouse model of depression generated by prolonged unpredicted mild stress. This effect is achieved through the reduction of oxidative stress
The Efficacy and Immune Mechanism of Thymosin Alpha 1 as a Valuable Adjunctive Therapy for Tuberculosis
No full textTuberculosis remains the leading cause of death among global infectious diseases with increasing challenges of antimicrobial resistance. Conventional anti-tuberculosis chemotherapy is aggravated by a limited success rate, a long course of treatment, and numerous side effects. Once again, we highlighted the significance of immuno-therapy. In this review, we focus on assessing the efficacy and safety of thymosin alpha 1 (Tα1) as a valuable adjunctive therapy for tuberculosis. We aim to examine the potential mechanism through which Tα1 influences the immune system of tuberculosis patients, intending to provide a theoretical foundation for its clinical applications. After reviewing the articles published in PubMed, Web of Science, Embase, BIOSIS Library, and China-national-knowledge-internet, we identified 21 clinical cohort studies investigating Tα1 as an auxiliary treatment for tuberculosis. These studies included 11 articles on pulmonary tuberculosis, 2 articles on tuberculous pleurisy, and 8 articles on intestinal tuberculosis. These studies have demonstrated the safety and effectiveness of Tα1, an immunomodulator, in the treatment of tuberculosis. The probable immune mechanism of Tα1 might involve the up-regulation of T lymphocyte (CD3+, CD4+), helper T 17 (Th17), natural killer (NK), interferon-γ (IFN-γ), and interleukin-2 (IL-2) levels. Consequently, Tα1 may be suggested as an effective and safe auxiliary treatment for mycobacterium tuberculosis infection in clinical settings. However, several key aspects regarding Tα1 remain unclear, including the molecular mechanism involved in Tα1s upregulation of immune cell differentiation and cytokine secretion, the synergistic association between Tα1 and anti-tuberculosis drugs, and its therapeutic dose and treatment duration for tuberculosis. Therefore, there is an urgent need to investigate these aspects and explore more scientific and effective treatment strategies to provide a reference for the treatment of tuberculosis
Myocardial perfusion stress test in women
Get PDFAim: The utility of the 99mTc-sestamibi myocardial perfusion stress imaging (MPI) over stress echo test (SEHO) in women with intermediate pre-test probability scores. Methodology: Our study included 98 women with suspected ischemic heart disease and intermediate pre-test probability scores who underwent MPI and SEHO. They were followed for 26 ± 6 months. The data about MACE and possible coronary angiography were collected. Results: The SEHO test was pathological in 31% of the study population. Almost half of those patients had atypical chest pain. MPI was positive in 32% of the examined group. In the follow-up period, MACE was present in 36 patients: PCI (20), CABG (8), acute coronary syndrome (8). The results of the MPI had a high statistically significant correlation with the coronary angiography findings in the follow-up period (p < 0.001, μ = 0.878). Additionally, the SEHO test and coronary angiography results correlated well (p < 0.05, μ = 0.582). However, MPI test result and SEHO result were not significantly associated with MACE based on Cox proportional hazard analyses (p > 0.05). Conclusion: MPI may be the complementary procedure for the evaluation of heart conditions in women with intermediatepre-test probability scores, since it correlates well with coronary angiography findings
Neurotensin Alleviates Chronic Pain after Spinal Cord Injury by Modulating Dopaminergic Neuron Activity in the Ventral Tegmental Area
No full textBackground: Neurotensin (NT), an endogenous neuropeptide, plays a crucial role in modulating dopaminergic transmission. Dopaminergic drugs may serve as an effective therapy against chronic pain, a frequent adverse symptom observed in spinal cord injury (SCI) patients. Therefore, we aimed to investigate whether the mechanism of NT for chronic pain after SCI involves the modulation of dopaminergic neuronal activity. Methods: The SCI rat model was used with or without NT administration based on the experimental design. Ultrasonic vocalizations (USVs) and von Frey filaments were performed to assess the effect of NT on pain behavior in SCI rats. Dopaminergic neuron firing and bursting within the ventral tegmental area (VTA) were examined using electrophysiology. Furthermore, the dopamine D2 receptor (D2DR) was quantified using quantitative real-time polymerase chain reaction and immunohistochemistry. Results: Significant spontaneous and induced pain could be observed in SCI rats along with a decrease in dopaminergic neuron firing and bursting activities as well as upregulation of D2DR expression (p < 0.001). Importantly, NT treatment significantly alleviated pain symptoms and promoted dopaminergic neuron firing and bursting activities in SCI rats (p < 0.001). Additionally, NT treatment diminished D2DR mRNA level and positive expression in SCI rats (p < 0.001). Conclusion: NT alleviates expression level of D2DR and activates dopaminergic firing and bursting activities in the VTA region, thereby relieving SCI-induced chronic pain
Do Different Interval Durations of High-Intensity Interval Training Influence Blood Glucose and Lactate, and Cause Hepatic Damage in Rats?
No full textBackground: High-intensity interval training (HIIT) is an exercise modality that can induce reactive oxygen species (ROS) production in skeletal muscles, the extent of which depends on the intensity, duration, and volume of exercise, potentially leading to oxidative stress. Objective: To analyze the effects of a single session of two HIIT protocols with different intensity levels on the markers of blood sugar, lactate, and hepatic damage in rats. Methods: Overall, 24 male Wistar rats were included in the study and divided into three groups (n = 8/group): control group (CG); short-interval HIIT (H1): HIIT involving 14 swimming periods lasting 20 s each, with 10-s intervals between each period, totaling a duration of 7 min; long-interval HIIT (H2): HIIT involving 14 swimming periods lasting 35 s each, with 25-s intervals between each period, totaling a duration of 14 min. Results: Regarding blood sugar levels, there were no significant differences in the H1 (113.00 ± 8.21 vs. 123.25 ± 10.78; p = 0.3303) and H2 (112.25 ± 12.55 vs. 114.25 ± 8.77; p = 0.9545) groups, respectively. Regarding lactate levels, there was a significant difference in both the groups compared with the CG (H1: 2.75 ± 0.55 vs. 10.06 ± 1.93; p = 0.0003; H2: 2.65 ± 1.07 vs. 9.99 ± 1.30; p = 0.0001). However, there was no difference in lactate levels between the H1 and H2 groups (10.06 ± 1.93 vs. 9.99 ± 1.30; p = 0.9965). Regarding hepatic damage, only H1 demonstrated a reduction in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels compared with CG (30% and 29.65%, respectively; p < 0.05). Conversely, there were no significant differences in the AST levels between both the groups and CG (16.40 ± 1.91 [H2] vs. 13.98 ± 1.06 [CG]; –14.75%; p = 0.0918; 11.48 ± 1.59 [H1] vs. 13.98 ± 1.06 [H2]; p = 0.0792). Additionally, there was no significant difference in the ALT levels between the HIIT groups (8.54 ± 1.70 [H1] vs. 10.32 ± 0.78 [H2]; p = 0.1756). Conclusions: A single session of HIIT training with different intensity levels does not induce changes in blood sugar and lactate markers. Furthermore, short-duration HIIT induced alterations in the hepatic markers (AST and ALT) compared with the control group. However, when comparing the HIIT groups, no significant alterations were observed following a single HIIT session
Chitosan Nanocapsules Boost Capsaicins Efficacy against Diabetes-Induced Cardiotoxicity in Rats
Get PDFBackground: Capsaicin is known for its therapeutic benefits, including anti-inflammatory, antioxidant, and cholesterol-lowering effects. However, its clinical application is limited by poor bioavailability, primarily due to its low solubility in water. Objective: To evaluate the efficacy of our newly optimized capsaicin-loaded chitosan nanocapsules (CAP@CS) in mitigating cardiotoxicity induced by type 2 diabetes mellitus (T2DM) and a high-fat diet in male Sprague Dawley rats. Methods: Nanocapsules containing capsaicin and chitosan were synthesized using the micro-emulsion technique and characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM), were administered to sixty male rats, which assigned to five groups: control, diabetic, diabetic with rosuvastatin, diabetic with capsaicin (CAP), and diabetic with CAP@CS. The inflammatory markers and biochemical indicators associated with myocardial damage, tissue oxidative stress, and inflammation were assessed. Results: DLS analysis revealed an average size of ~260 nm and a zeta potential of ~+18 mV. TEM images depicted circular and uniform nanocapsules. The diabetic + CAP@CS group showed more significant reductions in blood glucose and lipid levels compared to other diabetic groups, and markedly increased the concentrations of the antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), reduced glutathione, and upregulated nuclear factor erythroid 2-related factor 2 (NRF-2), and heme oxygenase-1 (HO-1) expressions more significantly than the diabetic + CAP group. CAP@CS upregulated nitric oxide concentrations and its bioregulator, inducible nitric oxide synthase (iNOS), demonstrating enhanced cardioprotection. The formula exhibited a more pronounced anti-inflammatory impact, as demonstrated by the tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) assessment. Histological investigations employing hematoxylin and eosin stain, Masson trichrome (MTC), and immunohistochemical analysis of α-smooth actin and desmin revealed the notable superiority of the new formula (CAP@CS) over capsaicin (CAP) in mitigating the myocardial damage mediated by diabetes. This efficacy was substantiated by assessments of myocardial protein content, malondialdehyde (MDA), heat shock protein 70 (HSP70) determination, alanine transaminase (ALT), aspartate transaminase (AST), and troponin levels. Conclusion: CAP@CS nanocapsules present a promising therapeutic strategy, improving for cardioprotection in T2DM, offering potential benefits such as improved efficacy, bioavailability, and reduced side effects
Ferroptosis is Involved in the Development of Severe Cutaneous Adverse Reactions through xCT/GPX4 Signaling Axis
No full textBackground: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening drug reactions of uncertain pathogenesis. Ferroptosis is an emerging, iron-dependent mode of regulated cell death. However, the correlation between SJS/TEN and ferroptosis has not been elucidated. The purpose of this study is to investigate the relationship between SJS/TEN and ferroptosis. Methods: Proteomic profiling of plasma proteins and imbalance of iron homeostasis of SJS/TEN patients are accompanied with high level of High Mobility Group Box 1 (HMGB1). Glutathione peroxidase 4 (GPX4) and system xc- (xCT) levels were detected by quantitative Polymerase Chain Reaction (qPCR) and Western blot. The morphology of cells was also observed by an electron microscope. Results: The increased serum iron in SJS/TEN patients and mitochondrial morphological alteration further suggested a link between ferroptosis and SJS/TEN. Compared with healthy control, the expressions of xCT, glutathione (GSH), and GPX4 were decreased in SJS/TEN patients, p < 0.05. Additionally, the results of validation experiment in vitro with blister fluids from SJS/TEN patients were also consistent. The expression levels of xCT (p < 0.05) and GPX4 (p < 0.001) were reduced after treatment with erastin and blister fluids, while this phenomenon was reversed by pretreatment with Ferrostatin-1 (Fer-1). Most importantly, we found that the serum concentration of ferritin showed a positive clinical correlation with the severity of drug eruption and the high scoring of severity-of-illness score for TEN (SCORTEN). Conclusions: The overall results show that ferroptosis is involved in the development of SJS/TEN and can be used as a potential target for therapeutic treatment
Effect of Polycomb Repressive Complex 2 on the Proliferation, Migration, Invasion, and Apoptosis of Gastric Cancer Cells by Targeting H3K27 Activation
No full textBackground: Gastric cancer is a globally prevalent malignancy characterized by dysregulated cellular processes including epigenetic modifications. However, the Polycomb Repressive Complex 2 (PRC2), a pivotal epigenetic regulator, modulates gene expression through trimethylation of histone H3 at lysine 27 (H3K27me3), thereby orchestrating cellular identity and function. Therefore, this study aimed to elucidate the impact of PRC2 and H3K27me3 on critical cellular behaviors, such as proliferation, migration, invasion, and apoptosis, which holds the potential to unveil novel insights into gastric cancer progression. Methods: Human gastric cancer cells NCI-N87 were seeded in a 6-well plate and were divided into the normal, siRNA-negative control (siRNA-NC), siRNA-Enhancer of zeste homolog 2 (siRNA-EZH2), and siRNA-SUZ12 polycomb repressive complex 2 subunit (siRNA-SUZ12) groups. The cells were transfected to knock down the expression of PRC2 core subunits, siRNA-Enhancer of zeste homolog 2 (EZH2) and SUZ12 polycomb repressive complex 2 subunit (SUZ12). Moreover, Western Blot analysis and Quantitative real-time reverse-transcription PCR (qRT-PCR) were carried out to determine the expression levels of the EZH2 and SUZ12 in gastric cancer cells. Furthermore, the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to examine cell proliferation, the Transwell assay was employed to determine cell migration and invasion, and flow cytometry was used to evaluate cell apoptosis rate. Additionally, the confocal laser scanning technique was utilized to assess H3K27 methylation in gastric cancer cells. Finally, the interaction between PRC2 and H3K27 was evaluated using co-immunoprecipitation (Co-IP). Results: Compared to the siRNA-NC group, there was a significant decrease in the levels of EZH2 protein and mRNA in the cells of the siRNA-EZH2 group and SUZ12 protein and mRNA in the siRNA-SUZ12 group (p < 0.05). Furthermore, both the siRNA-EZH2 and siRNA-SUZ12 groups showed significantly reduced cell survival rates, and decreased count of migrating and invading cells, while exhibited significantly increased apoptosis rate compared to the siRNA-NC group. Moreover, the expression level of H3K27me3 significantly elevated in these cells (p < 0.05). Additionally, Co-IP results revealed a significant interaction of EZH2 and SUZ12 with H3K27me3. Conclusion: This study delved into the impact of the PRC2 on gastric cancer cell behavior, focusing on the targeted regulation of histone H3K27me3. The findings suggest that PRC2 might modulate cellular proliferation, migration, invasion, and apoptosis within gastric cancer cells. Nevertheless, rigorous experimental validation is essential to establish causal relationship and gain deeper mechanistic insights into PRC2s role in gastric cancer
Preventive and Therapeutic Effect of Artesunate on Arthritis Induced by Bonvin Type II Collagen in Rats
No full textBackground and Objective: Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes joint deformities and even complete loss of joint function. Artesunate (ART) is an active ingredient in Chinese herbal medicines, usually used to treat malaria. This study aimed to investigate the effect of Artesunate on collagen-induced arthritis (CIA) in rats, along with its efficacy and underlying mechanism. Methods: The CIA rat model was created using bovine type II collagen and incomplete F-style adjuvants. The rats with CIA were divided into three groups: the Model group, the tripterygium hypoglaucum hutch (THH) group, and the ART group. The model group received 0.9% normal saline, the THH group was given a daily dose of 150 mg·kg-1 THH, and the ART group was given a daily dose of 10 mg·kg-1 artesunate for 30 days. The negative control (NC) group received only an equal volume of 0.9% normal saline. The body weight, arthritis index, and paw thickness of the rats were recorded throughout the treatment. The levels of tumor necrosis factor α (TNF-α) and interleukin 17A (IL-17A) in the serum of rats with CIA were assessed using enzyme-linked immunosorbent assay (ELISA). Furthermore, the indices of vital immune organs, including the thymus and spleen, were calculated. The hindpaw of each group was collected and subjected to histopathological examinations using hematoxylin-eosin (H&E) staining, safranin O-fast green staining and X-ray methods. Results: The arthritis index, the thickness of the foot, and the contents of IL-17A in the CIA model group were significantly increased compared to the NC group (p < 0.05). Moreover, synovial hyperplasia and cartilage damage were significantly decreased in the ART group (p < 0.05). However, the immune organ index and serum TNF-α level did not reach statistical significance (p > 0.05). Additionally, the serum IL-17A level was significantly lower than the model group (p < 0.05). Conclusion: Artesunate exerts a protective effect on joint damage in rats with CIA, which may reduce inflammation and delay the development of the disease by inhibiting the secretion of IL-17A
Antibacterial, Antitumor (Lung Cancer Cell H292) and Antioxidant Properties of Sicilian Prickly Pear Cactus (Opuntia Ficus-Indica) Cladode Extracts
No full textBackground: Methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) strains can colonize the lower respiratory tract, causing severe bacterial pneumonia. Such infections frequently occur in oncologic patients affected by lung cancer. Therefore, the present study aimed to explore the potential antibacterial and cytotoxic properties of Opuntia ficus-indica acetone and Opuntia ficus-indica diethyl ether extracts (OFI AE and OFI DEE) against Staphylococcus aureus strains and human mucoepidermoid pulmonary carcinoma cell line H292, respectively. In addition, the antioxidant activity of the two extracts was evaluated. Methods: The antimicrobial activity of OFI AE and OFI DEE against MSSA and MRSA strains was evaluated through the microdilution method. The antibiofilm effect of OFI extracts was determined by the crystal violet assay. Moreover, the potential synergistic activity between OFI extracts and the antibiotic Gentamycin (GEN) was tested using the checkerboard assay. The cytotoxic activity against H292 cells was investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrasodium bromide (MTT) and flow cytometry assays. Furthermore, oxidative stress and antioxidant capacity of the extract were measured by extracellular reactive oxygen species (ROS) formation and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, respectively. Finally, the chemical composition of the two phytoextracts was analyzed by Ultra High-Performance Liquid Chromatography-Mass Spectrometry. Results: Our results show that both extracts inhibited the growth of MSSA and MRSA strains, although they were not able to counteract biofilm formation. However, the combination of the extracts with GEN potentiated the activity of the antibiotic treatment. Furthermore, OFI AE treatment showed a potent cytotoxic effect on H292 cells following ROS formation. Finally, both extracts showed no significant antioxidant activity and the chemical analysis revealed a high content of polyphenols and flavonoids, which could be responsible for the observed biological effects of the OFI extracts. Conclusions: OFI extracts are a promising natural source of antibacterial and anticancer agents endowed with beneficial effects on human health