The Role of Daily Steps in the Treatment of Major Depressive Disorder: Secondary Analysis of a Randomized Controlled Trial of a 6-Month Internet-Based, Mindfulness-Based Cognitive Behavioral Therapy Intervention for Youth.

BACKGROUND: Current evidence supports physical activity (PA) as an adjunctive treatment for major depressive disorder (MDD). Few studies, however, have examined the relationship between objectively measured PA and MDD treatment outcomes using prospective data. OBJECTIVE: This study is a secondary analysis of data from a 24-week internet-based, mindfulness-based cognitive behavioral therapy program for MDD. The purpose of this analysis was twofold: (1) to examine average daily step counts in relation to MDD symptom improvement, and whether pain moderated this relationship; and (2) to examine whether changes in step activity (ie, step trajectories) during treatment were associated with baseline symptoms and symptom improvement. METHODS: Patients from the Centre for Addiction and Mental Health were part of a randomized controlled trial evaluating the effects of internet-based, mindfulness-based cognitive behavioral therapy for young adults (aged 18-30 years old) with MDD. Data from 20 participants who had completed the intervention were analyzed. PA, in the form of objectively measured steps, was measured using the Fitbit-HR Charge 2 (Fitbit Inc), and self-reported depression severity was measured with the Beck Depression Inventory-II (BDI-II). Linear regression analysis was used to test PA's relationship with depression improvement and the moderating effect of pain severity and pain interference. Growth curve and multivariable regression models were used to test longitudinal associations. RESULTS: Participants walked an average of 8269 steps per day, and each additional +1000-step difference between participants was significantly associated with a 2.66-point greater improvement (reduction) in BDI-II, controlling for anxiety, pain interference, and adherence to Fitbit monitoring (P=.02). Pain severity appeared to moderate (reduce) the positive effect of average daily steps on BDI-II improvement (P=.03). Higher baseline depression and anxiety symptoms predicted less positive step trajectories throughout treatment (Ps≤.001), and more positive step trajectories early in the trial predicted greater MDD improvement at the end of the trial (Ps<.04). However, step trajectories across the full duration of the trial did not significantly predict MDD improvement (Ps=.40). CONCLUSIONS: This study used objective measurements to demonstrate positive associations between PA and depression improvement in the context of cognitive behavioral treatment. Pain appeared to moderate this relationship, and baseline symptoms of anxiety and depression predicted PA trajectories. The findings inform future interventions for major depression. Future research with larger samples should consider additional moderators of PA-related treatment success and the extent to which outcomes are related to PA change in multimodal interventions. TRIAL REGISTRATION: Clinical Trials.gov NCT03406052; https://www.clinicaltrials.gov/ct2/show/NCT03406052. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/11591.

Bioactive compounds and biomedical applications of endophytic fungi: a recent review.

Human life has been significantly impacted by the creation and spread of novel species of antibiotic-resistant bacteria and virus strains that are difficult to manage. Scientists and researchers have recently been motivated to seek out alternatives and other sources of safe and ecologically friendly active chemicals that have a powerful and effective effect against a wide variety of pathogenic bacteria as a result of all these hazards and problems. In this review, endophytic fungi and their bioactive compounds and biomedical applications were discussed. Endophytes, a new category of microbial source that can produce a variety of biological components, have major values for study and broad prospects for development. Recently, endophytic fungi have received much attention as a source for new bioactive compounds. In addition, the variety of natural active compounds generated by endophytes is due to the close biological relationship between endophytes and their host plants. The bioactive compounds separated from endophytes are usually classified as steroids, xanthones, terpenoids, isocoumarins, phenols, tetralones, benzopyranones and enniatines. Moreover, this review discusses enhancement methods of secondary metabolites production by fungal endophytes which include optimization methods, co-culture method, chemical epigenetic modification and molecular-based approaches. Furthermore, this review deals with different medical applications of bioactive compounds such as antimicrobial, antiviral, antioxidant and anticancer activities in the last 3 years.

Ziziphus spina-christi extract-stabilized novel silver nanoparticle synthesis for combating Fusarium oxysporum-causing pepper wilt disease: in vitro and in vivo studies.

The novelty of the present study is studying the ability of aqueous Ziziphus spina-christi leaves' extract (ZSCE) to produce eco-friendly and cost-effective silver nanoparticles (Ag NPs) against Fusarium wilt disease. Phytochemical screening of ZSCE by HPLC showed that they contain important antimicrobial substances such as Rutin, Naringin, Myricetin, Quercetin, Kaempferol, Hesperidin, Syringeic, Eugenol, Pyrogallol, Gallic and Ferulic. Characterization methods reveal a stable Ag NPs with a crystalline structure, spherical in shape with average particle size about 11.25 nm. ZSCE and Ag NPs showed antifungal potential against F. oxysporum at different concentrations with MIC of Ag NPs as 0.125 mM. Ag NPs treatment was the most effective, as it gave the least disease severity (20.8%) and the highest protection rate (75%). The application of ZSCE or Ag NPs showed a clear recovery, and its effectiveness was not limited for improving growth and metabolic characteristics only, but also inducing substances responsible for defense against pathogens and activating plant immunity (such as increasing phenols and strong expression of peroxidase and polyphenol oxidase as well as isozymes). Owing to beneficial properties such as antifungal activity, and the eco-friendly approach of cost and safety, they can be applied in agricultural field as novel therapeutic nutrients.

Ferric Oxide Colloid: Towards Green Nano-Fertilizer for Tomato Plant with Enhanced Vegetative Growth and Immune Response Against Fusarium Wilt Disease.

Global food crisis due to climate change, pandemic COVID-19 outbreak, and Russia-Ukraine conflict leads to catastrophic consequences; almost 10 percent of the world's population go to bed hungry daily. Narrative solution for green agriculture with high vegetation and crop yield is mandatory; novel nanomaterials can improve plant immunity and restrain plant diseases. Iron is fundamental nutrient element; it plays vital role in enzyme activity and RNA synthesis; furthermore it is involved in photosynthesis electron-transfer chains. This study reports on the facile synthesis of colloidal ferric oxide nanoparticles as novel nano-fertilizer to promote vegetation and to suppress Fusarium wilt disease in tomato plant. Disease index, protection percent, photosynthetic pigments, and metabolic indicators of resistance in plant as response to induction of systemic resistance (SR) were recorded. Results illustrated that Fe2O3 NPs had antifungal activity against F. oxysporum. Fe2O3 NPs (at 20 µg/mL) was the best treatment and reduced percent disease indexes by 15.62 and gave highly protection against disease by 82.15% relative to untreated infected plants. Fe2O3 NPs treatments in either (non-infected or infected) plants showed improvements in photosynthetic pigments, osmolytes, and antioxidant enzymes activity. The beneficial effects of the synthesized Fe2O3 NPs were extended to increase not only photosynthetic pigments, osmolytes contents but also the activities of peroxidase (POD), polyphenol oxidase (PPO), catalase (CAT) and superoxide dismutase (SOD), enzymes of the healthy and infected tomato plants in comparison with control. For, peroxidase and polyphenol oxidase activities it was found that, application of Fe2O3 NPs (10 µg/mL) on challenged plants offered the best treatments which increased the activities of POD by (34.4%) and PPO by (31.24%). On the other hand, application of Fe2O3 NPs (20 µg/mL) on challenged plants offered the best treatments which increased the activities of CAT by (30.9%), and SOD by (31.33%). Supplementary Information: The online version contains supplementary material available at 10.1007/s10904-022-02442-6.

The potential impact of Octopus cyanea extracts to improve eggplant resistance against Fusarium-wilt disease: in vivo and in vitro studies.

The novelty of the present research is conducting a new method in the systemic resistance of plant diseases by using distinct marine extracts. The ability of two octopus extracts to reduce the wilt disease caused by Fusarium oxysporum was observed. The applied methods are soaked roots (SR) and foliar shoots (FS). The antioxidant enzyme activities, percent disease index (PDI), and growth parameters were measured. In vitro antifungal potential of the octopus extracts against F. oxysporum was examined. The obtained result shows that SR extracts reduced PDI. Additionally, all the tested treatments promoted the growth and photosynthetic pigments of the infected plants. SR (in ethanolic extracts) was the most prominent inducer which offered a high advancement in the total soluble protein contents. Also, SR (in methanolic extracts) was the most suitable inducer which provided a very necessary development not only in the total phenol but also in the peroxidase (POD) and polyphenol oxidase (PPO) activities. GC-MS investigation of the octopus extracts exhibited that the compounds which possess antifungal activity were furoscrobiculin B and/or eugenol. They demonstrated a notable antifungal potential against F. oxysporum with a maximum activity of 38.5 and 12.7 mm ZOI after the treatment with the ethanolic and methanolic extract, respectively. FTIR results illustrated the functional group of the compound responsible for the antifungal activity. Additionally, an atomic absorption result reveals that there are traces of metals detected such as Pb, Ag, Cu, Zn, and Mg. The antifungal activity was decreased as the concentrations were reduced. Accordingly, the present extracts may be used as the vital agents in the agricultural field to restrain the plant pathogenic fungi, especially F. oxysporum from a proliferation.

Nanoparticles induce genetic, biochemical, and ultrastructure variations in Salvadora persica callus.

BACKGROUND: Salvadora persica is an endangered medicinal plant due to difficulties in its traditional propagation. It is rich in bioactive compounds that possess many pharmaceutical, antimicrobial activities and widely used in folk medicine. The current study aims at in vitro propagation of Salvadora persica and the application of different nanoparticles (NPs) to induce the synthesis of bioactive and secondary metabolites within the plant. The cellular and genetic responses to the application of different NPs were evaluated. RESULTS: The impact of nanoparticles NPs (ZnO, SiO2, and Fe3O4) on callus growth of Salvadora persica and the production of its active constituent benzyl isothiocyanate was examined, regarding some oxidative stress markers, antioxidant enzymes, and genetic variabilities. An encouraging impact of 0.5 mg/l ZnO NPs on benzyl isothiocyanate production was shown reaching up to 0.905 mg/g callus fresh weight in comparison to 0.539 mg/g in control callus. This was associated with decreasing hydrogen peroxide content and increasing superoxide dismutase and peroxidase activities. The deposition of the NPs on cellular organelles was detected using a transmission microscope. Fifteen Inter-Simple Sequence Repeats (ISSR) primers detected an overall, 79.1% polymorphism among different treatments. A reduction in genomic DNA template stability (GTS) was made and was more pronounced in higher doses of different NPs. CONCLUSION: This study is a stepping stone in developing a productive protocol for in vitro production of benzyl isothiocyanate from Salvadora persica using NPs as a valuable anticancer compound.

An Overview of the Antioxidant Effects of Ascorbic Acid and Alpha Lipoic Acid (in Liposomal Forms) as Adjuvant in Cancer Treatment.

Antioxidants are known to minimize oxidative stress by interacting with free radicals produced as a result of cell aerobic reactions. Oxidative stress has long been linked to many diseases, especially tumours. Therefore, antioxidants play a crucial role in the prevention or management of free radical-related diseases. However, most of these antioxidants have anticancer effects only if taken in large doses. Others show inadequate bioavailability due to their instability in the blood or having a hydrophilic nature that limits their permeation through the cell membrane. Therefore, entrapping antioxidants in liposomes may overcome these drawbacks as liposomes have the capability to accommodate both hydrophilic and hydrophobic compounds with a considerable stability. Additionally, liposomes have the capability to accumulate at the cancer tissue passively, due to their small sizes, with enhanced drug delivery. Additionally, liposomes can be engineered with targeting moieties to increase the delivery of chemotherapeutic agents to specific tumour cells with decreased accumulation in healthy tissues. Therefore, combined use of liposomes and antioxidants, with or without chemotherapeutic agents, is an attractive strategy to combat varies tumours. This mini review focuses on the liposomal delivery of selected antioxidants, namely ascorbic acid (AA) and alpha-lipoic acid (ALA). The contribution of these nanocarriers in enhancing the antioxidant effect of AA and ALA and consequently their anticancer potentials will be demonstrated.

Curcumin-loaded PLA-PEG copolymer nanoparticles for treatment of liver inflammation in streptozotocin-induced diabetic rats.

This report focused on loading curcumin (CUR) drug into biodegradable Polylactide-poly(ethylene glycol) (PLA-PEG) copolymer nanoparticles as an effective anti-inflammatory agent in vivo to overcome the limitations resulted from the free CUR. By a simple nano-emulsification technique, hydrophobic CUR was loaded into hydrophobic polymer's segments and stabilized by cationic surfactant. They were then characterized by DLS, TEM, and SEM techniques providing monodispersed and spherical nanoparticles with an average diameter of 117 nm and high surface charge of +35 mV. Thereafter, they were orally administrated into five groups of rats, typically, control (healthy rats), streptozotocin (STZ)-induced diabetic rats, diabetics treated with free CUR, diabetics treated with PLA-PEG NPs, and diabetics treated with CUR-encapsulated PLA-PEG NPs. Next, complete blood analyses were assessed including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and nuclear factor kappa B (NF-Ò¡B), reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), cyclooxygenase (COX-2), Peroxisome proliferator-activated receptors (PPAR-γ) and transforming growth factor-ß1 (TGF-ß1). The obtained results demonstrated that diabetes initially produced liver inflammation in rats manifested by leveraging the mean levels of serum AST, ALT inducing oxidative stress resulting in a clear increase in the levels of hepatic MDA and NO concomitant with a remarkable decrease in GSH. Moreover, diabetes significantly increased serum NF-Ò¡B, hepatic COX-2 and TGF-ß1, while highly reduced hepatic PPAR-γ. In contrast, both CUR free and CUR-encapsulated NPs ameliorated the negative changes in diabetes but CUR-encapsulated NPs showed more pronounced treated effect than free CUR. In addition, histopathological investigations were performed on the liver tissues of all groups, showing a mitigation in inflammation while treating with CUR-NPs.

Al-hijamah (wet cupping therapy of prophetic medicine) significantly and safely reduces iron overload and oxidative stress in thalassemic children: a novel pilot study.

BACKGROUND: Thalassemia is a major health problem due to iron overload, iron deposition and oxidative stress-induced tissue damage. Here, we introduce Al-hijamah (a minor surgical excretory procedure) as a novel percutaneous iron excretion therapy. Al-hijamah is a wet cupping therapy of prophetic medicine, and prophet Muhammad, peace be upon him, strongly recommended Al-hijamah, saying: "The best of your treatment is Al-hijamah". AIM OF THE STUDY: Our study aimed at investigating the safety, iron chelation, pharmacological potentiation and oxidant clearance effects exerted by Al-hijamah to thalassemic children. PATIENTS AND METHODS: Ethical committee's approval and patients' written agreement consents were obtained. We treated 20 thalassemic children (15 males and five females aged 9.07±4.26 years) with iron chelation therapy (ICT) plus Al-hijamah (using sterile disposable sets and in a complete aseptic environment) vs a control group treated with ICT only. This clinical trial was registered in the ClinicalTrial.gov registry under the name "Study of the Therapeutic Benefits of Al-hijamah in Children with Beta Thalassemia Major" (identifier no NCT 02761395) on 30 January 2016. RESULTS: Al-hijamah was quite simple, safe, effective, tolerable (with no side effects) and time-saving procedure (30-60 minutes). A single session of Al-hijamah significantly reduced iron overload (P<0.001) in all thalassemic children. Al-hijamah significantly decreased serum ferritin by 25.22% (from 3,778.350±551.633 ng/mL to 2,825.300±558.94 ng/mL), significantly decreased oxidative stress by 68.69% (P<0.05; serum malondialdehyde dropped from 42.155±12.42 to 13.195±0.68 nmol/L), exerted pharmacological potentiation to ICT and significantly increased total antioxidant capacity (P<0.001) by 260.95% (from 13.195±0.68 nmol/L to 42.86±12.40 nmol/L through excreting reactive oxygen species). Moreover, therapeutic indices for evaluating Al-hijamah were promising. CONCLUSION: Al-hijamah is a novel, safe, effective percutaneous iron excretion therapy through percutaneous iron excretion with minimal blood loss in agreement with the evidence-based Taibah mechanism. Al-hijamah is an effective outpatient hematological procedure that is safer than many pediatric procedures such as catheterization, hemofiltration and dialysis. Increasing the number of cups during Al-hijamah session or the number of sessions reduces iron overload more strongly. Medical practice of Al-hijamah is strongly recommended in hospitals.

Anticonvulsant profiles of certain new 6-aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones and 1-aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones.

Synthesis and anticonvulsant potential of certain new 6-aryl-9-substituted-6,9-diazaspiro[4.5]decane-8,10-diones (6a-l) and 1-aryl-4-substituted-1,4-diazaspiro[5.5] undecane-3,5-diones (6m-x) are reported. The intermediates 1-[(aryl)(cyanomethyl)amino] cycloalkanecarboxamides (3a-f) were prepared via adopting Strecker synthesis on the proper cycloalkanone followed by partial hydrolysis of the obtained nitrile functionality and subsequent N-cyanomethylation. Compounds 3a-f were subjected to complete nitrile hydrolysis to give the respective carboxylic acid derivatives 4a-f which were cyclized under mild conditions to give the spiro compounds 5a-f. Ultimately, compounds 5a-f were alkylated or aralkylated to give the target compounds 6a-i and 6m-u. On the other hand, compounds 6j-l and 6v-x were synthesized from the intermediates 5a-f through alkylation, dehydration and finally tetrazole ring formation. Anticonvulsant screening of the target compounds 6a-x revealed that compound 6g showed an ED50 of 0.0043 mmol/kg in the scPTZ screen, being about 14 and 214 fold more potent than the reference drugs, Phenobarbital (ED50 = 0.06 mmol/kg) and Ethosuximide (ED50 = 0.92 mmol/kg), respectively. Compound 6e exhibited an ED50 of 0.019 mmol/kg, being about 1.8 fold more potent than that of the reference drug, Diphenylhydantoin (ED50 = 0.034 mmol/kg) in the MES screen. Interestingly, all the test compounds 6a-x did not show any minimal motor impairment at the maximum administered dose in the neurotoxicity screen.

Effect of iron deficiency anemia and its treatment on cell mediated immunity.

Iron deficiency anemia (IDA) is one of the most prevalent micronutrient deficiencies particularly in the developing countries. While there is evidence of an altered immune profile in iron deficiency, the exact immunoregulatory role of iron is not known. Knowledge particularly in children, who are vulnerable to iron deficiency and infection, is lacking. We aimed to study the effects of IDA and its treatment with oral iron supplementation on cell-mediated immunity. The levels of T-lymphocytes, their CD4(+), CD8(+) and CD1a(+) subsets, transferrin receptor (CD71) and serum ferritin were evaluated in 40 iron-deficient and 40 healthy children. The impact of oral iron supplementation for three months on the same parameters was also noted in children with IDA. The level of mature T-lymphocytes (CD4(+) and CD8(+)) was significantly lower (P<0.001) while that of the immature T-cells (CD1a(+)) was significantly higher (p<0.001) in IDA children compared to the control. The mature T-cell count was significantly improved after iron therapy. In spite of significant reduction in the immature T-cells (CD1a(+)) level after iron supplementation, it was significantly higher than the control. The present study demonstrated that T-lymphocytes maturation was defective in IDA and improved partially after 3 months of iron supplementation. Therefore, longer time of iron therapy may be required to induce complete maturation of T-lymphocytes.