BACKGROUND: Allergic rhinitis (AR) or seasonal allergy characterized by sneezing, nasal congestion, nasal itching, and nasal discharge, triggered by immune reactions to environmental allergens. Present day customers also monitor the personal improvements in the area of Evidence-Based natural medicines/supplements.
METHODS: A randomized, double-blind, placebo-controlled study was conducted on 65 participants aged 18 to 60 years having 2 or more allergic symptoms like sneezing, rhinorrhoea, nasal obstruction, and nasal itching for a cumulative period greater than 1 hour per day. The study participants received a capsule of NSO (250 mg) with 2.5 mg piperine (BioPerine) as a bioavailability enhancer or a placebo, twice a day, after food for 15 days. The primary objectives were evaluated by mean change in Total Nasal Symptom Score and the duration of AR symptoms per day from baseline to Day 15. Secondary endpoints were changes in Total Ocular Symptoms Score, AR symptom frequency and severity, serum Immunoglobulin E levels, and Patient Global Impression of Change scale. Adverse events were monitored throughout the study.
RESULTS: Sixty-five patients were enrolled and all of them completed the study, N = 33 in NSO and N = 32 in placebo. A significant reduction in Total Nasal Symptom Score and Total Ocular Symptoms Score was observed in the NSO group compared to the placebo, highlighting the potential of NSO in alleviating AR symptoms. The episodes of AR symptoms per day and the frequency of symptoms in 24 hours reduced significantly in 15 days in both groups, but the extent of improvement was significantly higher in NSO compared to placebo. Improvement in Patient Global Impression of Change was also significantly better in NSO compared to the placebo. Serum Immunoglobulin E levels decreased in NSO but were not significantly different from placebo. No clinically significant changes were observed in vital signs, liver and renal function, lipid profile, hematology, fasting blood sugar, or urine analysis at the end of the study.
CONCLUSIONS: The result of the study demonstrates that NSO 250 mg with 2.5 mg piperine is an effective and well-tolerated supplement for the management of AR symptoms.

Thymoquinone (TQ) is one of the main phytochemical bioactive ingredients in Nigella sativa, with reported immunity-boosting properties. The current study evaluated the anti-inflammatory effect of TQ against inflammation brought on by free fatty acid Palmitate (PA) using macrophages raw 264.7 cell line. Data revealed that TQ significantly improved the viability of basal and PA stimulated Macrophages at concentrations of 50 and 100 μg/mL. Also, TQ significantly reduced nitric oxide and triglyceride levels in PA-stimulated macrophages at concentrations of 50 and 100 μg/mL. The pro-inflammatory cytokines studies revealed that PA significantly increased the release of the cytokines TNF-α, MHGB-1, IL-1β, and IL-6. TQ at concentrations 25, 50, and 100 μg/ml significantly decreases the release of the studied cytokines in PA-stimulated macrophages to variable extents with parallel inhibition to their corresponding gene expression. Bioenergetic assays showed that PA significantly decreased cellular ATP, mitochondrial complexes I and III activities and mitochondrial membrane potential with a subsequent significant increase in lactate production. At the same time, TQ can alleviate the effect of PA on macrophages\' bioenergetics parameters to variable extent based on TQ concentration. To conclude, TQ could mitigate palmitate-induced inflammation and cytotoxicity in macrophages by improving macrophage viability and controlling cytokine release with improved PA-induced bioenergetics disruption.

CCl4 toxicity is a fatal condition that can cause numerous organ dysfunctions. We evaluated and compared the protective effects of cuminaldehyde (CuA), thymoquinone (TQ), and gallic acid (GA) on CCl4-induced pulmonary and renal toxicity in rats. The impacts of these compounds on CCl4-induced oxidative stress, inflammation, and morphological alterations were examined. The results showed that the compounds under investigation prevented CCl4 from significantly increasing pulmonary and renal lipid peroxidation and NO levels, as well as massively depleting GSH levels and GPX and SOD activities. Moreover, they suppressed the CCl4-induced increase in mucus secretion in the lung and upregulated the gene expression of pulmonary and renal NF-ҡB, iNOS, TNF-α, and COX-2. The heatmap cluster plots showed that GA and TQ had better protective potencies than CuA. The external organ morphology, histopathological results, and chest X-ray analysis confirmed the toxicity of CCl4 and the protective influences of the tested compounds in both the lungs and kidneys of rats. These compounds displayed predicted competitive inhibitory effects on iNOS activity and may block the IL-13α2 receptor, as revealed by molecular docking analysis. Thus, CuA, TQ, and GA, particularly the latter two, are prospective protective compounds against the pulmonary and renal toxicity caused by CCl4.

OBJECTIVE: To evaluate the correlation between the antiannexin A5 antibodies (aAnxA5) multiples of median (MOM) and subsequent pregnancy outcomes in women with recurrent miscarriage (RM).
METHODS: Totally, 310 RM women were included in this study and grouped into tertiles according to their MOM of preconception aAnxA5 circulating levels determined by ELISA. The effect of aAnxA5 on the pregnancy outcomes was performed using multiple logistic regression. The outcomes included early miscarriage (before 10 weeks of gestation), late miscarriage (between 10 and 24 weeks), ongoing pregnancy (beyond 10 weeks), and live birth (after 24 weeks) characterized by pregnancy with fetal heartbeat.
RESULTS: For each unit increase in aAnxA5 MOM, the odds of live birth after 24 weeks and ongoing pregnancy were reduced by 40.2% (OR = .598; 95%CI 0.406-0.882, P = .010) and 38.1% (OR = .619; 95%CI 0.424-0.904, P = .013), respectively, after adjusting for demographic and clinical characteristics. The rise in aAnxA5 MOM was associated with an increased risk of early miscarriage (OR = 1.616; 95%CI 1.106-2.361, P = .013) and miscarriage (early + late miscarriage) (OR = 1.671; 95%CI 1.134-2.464, P = .010). Further subgroup analyses showed a decreased risk of live birth rates after 24 weeks of gestation in the two subgroups: maternal age ≥35 years (OR = .131; 95%CI 0.026-0.652), and previous pregnancy loss ≥ 3 (OR = .381; 95%CI 0.173-0.837).
CONCLUSIONS: Higher preconception aAnxA5 MOM levels in women with RM may be linked with a decreased risk of live birth after 24 weeks and an increased risk of early miscarriage, especially in individuals aged ≥35 years or with previous pregnancy losses ≥3.

Thymoquinone has antioxidant and anticancer effects. This study investigates the cytotoxic, genotoxic, and apoptotic effects of black seed and its active ingredient, thymoquinone on colorectal cancer cells. The antioxidant content of Black seed methanolic extracts (BSME) with different concentrations (50, 500 and 1000 μg/mL) were determined by the photometric methods. The reactive oxygen production (iROS) of BSME and thymoquinone on colorectal cancer cells (LoVo) and normal epithelial cells (CCD18Co) were analyzed by the fluorometric methods. A luminometric glutathione kit was employed to observe the changes in intracellular glutathione (GSH) levels. Cytotoxicity was determined by the ATP method, genotoxicity was determined by Comet Assay, and the apoptosis was identified by the Acridine Orange/Ethidium Bromide (AO/EB) double dye method. The cytotoxicity was increased by BSME and thymoquinone in LoVo cells in a dose-dependent manner (p<0.001). BSME and thymoquinone also increased iROS, and induced apoptosis and DNA damage (p<0.001). High doses of BSME and thymoquinone on cancer and healthy cells have cytotoxic, genotoxic and apoptotic effects with pro-oxidant effects. Colorectal cancer cells are more sensitive than healthy cells.

Ruxolitinib (RUX) is a potent drug that has been approved by the Food and Drug Administration for the treatment of myelofibrosis, polycythemia vera, and graft-versus-host disease. This study describes the formation of colored charge-transfer complexes (CTCs) of RUX, an electron donor, with chloranilic acid (CLA) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the π-electron acceptors. The CTCs were characterized using UV-visible spectrophotometry. The formation of CTCs in methanol was confirmed via formation of new absorption bands with maximum absorption at 530 and 470 nm for CTCs with CLA and DDQ, respectively. The molar absorptivity and other physicochemical and electronic properties of CTCs were determined. The molar ratio was found to be 1:1 for both CTCs with CLA and CTCs with DDQ. The site of interaction on RUX molecules was assigned and the mechanisms of the reactions were postulated. The reactions were employed as basis for the development of a novel green and one-step microwell spectrophotometric method (MW-SPM) for high-throughput quantitation of RUX. Reactions of RUX with CLA and DDQ were carried out in 96-well transparent plates, and the absorbances of the colored CTCs were measured by an absorbance microplate reader. The MW-SPM was validated according to the ICH guidelines. The limits of quantitation were 7.5 and 12.6 µg/mL for the methods involving reactions with CLA and DDQ, respectively. The method was applied with great reliability to the quantitation of RUX content in Jakavi® tablets and Opzelura® cream. The greenness of the MW-SPM was assessed by three different metric tools, and the results proved that the method fulfills the requirements of green analytical approaches. In addition, the one-step reactions and simultaneous handling of a large number of samples with micro-volumes using the proposed method enables the high-throughput analysis. In conclusion, this study describes the first MW-SPM, a valuable analytical tool for the quality control of pharmaceutical formulations of RUX.

Hepatocellular carcinoma is the most common primary malignant tumor of the liver, and its incidence is increasing worldwide. There is a need to develop new therapeutic strategies to treat the disease. In this study, we synthesised the oxime derivative of thymoquinone and investigated cytotoxicity, genotoxicity, and apoptosis in hepatocellular cancer cells. The synthesised thymoquinone-oxime structure was confirmed by NMR. After incubating the hepatocellular cancer cell line for 24 h, the cytotoxicity ATP by luminometric, intracellular reactive oxygen species, and intracellular calcium by fluorometric. The mitochondrial membrane potential was determined by flow cytometry. DNA damage by alkaline single-cell gel electrophoresis, and apoptosis damage by acridine orange/ethidium bromide double dye method. Concentrations of thymoquinone-oxime statistically increased cytotoxicity, intracellular reactive oxygen species, intracellular calcium, apoptosis, and DNA damage in a concentration-dependent manner. Mitochondrial membrane potential and glutathione levels are also decreased. These findings show that thymoquinone-oxime has an anti-tumor effect on hepatocellular carcinoma cells.
Among many herbs, Black seed (Nigella sativa) belonging to the Ranunculaceae family has been recognised worldwide as one of the most valuable nutrient-rich herbsThere is no relevant data on the effect of the newly synthesised oxime derivative of TQ (TQ-ox) in cancer cells HEP-G2A new TQ derivative has a higher anti-tumor effect on hepatocellular carcinoma.

OBJECTIVE: Thymoquinone (TQ) is a component derived from the volatile oil of Nigella sativa. Fenton reaction induction is a well-known strategy to prevent the growth of cancer cells which can stimulate by hydrogen peroxide. This study was designed to investigate the TQ effects on hydrogen peroxide-induced cytotoxicity.
METHODS: In this study, HepG2 cell survival, reactive oxygen species (ROS) production, cell membrane integrity, and changes of superoxide dismutase (SOD)/ catalase (CAT) activity were evaluated following incubation of HepG2 cells with 31 μM hydrogen peroxide and different concentrations of TQ (18.5, 37 and 75 μM). In addition, molecular docking studies on the interference of TQ with CAT/SOD enzymes were investigated.
RESULTS: Our findings showed that TQ low concentration can increase the survival of HepG2 cells when exposed to hydrogen peroxide, and on the contrary, its high concentration can potentiate cytotoxicity induced by hydrogen peroxide. The TQ alongside hydrogen peroxide increased the production of ROS, which was related to increase CAT and SOD activity in the HepG2 cells. Molecular docking findings showed that TQ effects on the formation of free radicals were not related to its chemical interference with the structure of the SOD/CAT molecules.
CONCLUSIONS: Fenton reaction induction may increase the effectiveness of TQ in preventing HepG2 cells proliferation.

Depression is the most common mental disorder among people living with HIV/AIDS and has a negative impact on HIV treatment outcomes. Training lay HIV counselors to identify and manage depression may contribute to improved patient access and adherence to treatment, and reduce stigma and discrimination among lay health workers toward both HIV and depression. The purpose of this study was to assess the current knowledge and attitudes of lay HIV counselors toward managing depression in primary care in Mozambique.
We conducted a mixed-methods cross-sectional study to assess depression-related knowledge and attitudes among lay HIV counselors in 13 primary healthcare facilities in Mozambique. We used the quantitative Depression Attitude Questionnaire (DAQ) scale, followed by open-ended questions to further explore three key DAQ domains: the nature of depression, treatment preferences, and professional attitudes or reactions.
The sample included 107 participants (77.6% female, mean age: 32.3 years, sd = 7.4). Most (82.2%) had less than a high/technical school education. Findings suggested that some HIV counselors had knowledge of depression and described it as a cluster of psychological symptoms (e.g., deep sadness, anguish, apathy, isolation, and low self-esteem) sometimes leading to suicidal thoughts, or as a consequence of life stressors such as loss of a loved one, abuse, unemployment or physical illness, including being diagnosed with HIV infection. HIV counselors identified talking to trusted people about their problems, including family and/or counseling with a psychotherapist, as the best way for patients to deal with depression. While acknowledging challenges, counselors found working with patients with depression to be rewarding.
Lay health counselors identified HIV and psychosocial issues as key risk factors for depression. They believed that the treatment approach should focus on social support and psychotherapy.

The molecular chaperone HSP90 plays an essential role in cancer occurrence and development. Therefore, it is an important target for the development of anticancer drugs. 1,3-Dibenzyl-2-aryl imidazolidine (8) is a previously reported inhibitor of HSP90; however, its anticancer activity is poor. In this work, chemical modification of 8 led to the discovery of 2,4-diarylimidazoles and 2,4-bis(benzyloxy)-5-arylpyrimidines as two types of novel HSP90 N-terminal inhibitors. 16l and 22k exhibited antiproliferative activity against multiple breast cancer cell lines with IC50 values at the low micromolar level. 16l and 22k induced significant degradation of the client proteins AKT and ERK and a lower level of the heat shock response in comparison with tanespimycin (17-AAG). 22k exhibited a strong affinity for the HSP90α N-terminus with an IC50 value of 0.21 μM. A molecular docking study revealed that 16l and 22k successfully bind to the geldanamycin binding site at the N-terminus of HSP90α.