Mechanisms of Bleomycin-induced Lung Fibrosis: A Review of Therapeutic Targets and Approaches.

Pulmonary toxicity is a serious side effect of some specific anticancer drugs. Bleomycin is a well-known anticancer drug that triggers severe reactions in the lungs. It is an approved drug that may be prescribed for the treatment of testicular cancers, Hodgkin's and non-Hodgkin's lymphomas, ovarian cancer, head and neck cancers, and cervical cancer. A large number of experimental studies and clinical findings show that bleomycin can concentrate in lung tissue, leading to massive oxidative stress, alveolar epithelial cell death, the proliferation of fibroblasts, and finally the infiltration of immune cells. Chronic release of pro-inflammatory and pro-fibrotic molecules by immune cells and fibroblasts leads to pneumonitis and fibrosis. Both fibrosis and pneumonitis are serious concerns for patients who receive bleomycin and may lead to death. Therefore, the management of lung toxicity following cancer therapy with bleomycin is a critical issue. This review explains the cellular and molecular mechanisms of pulmonary injury following treatment with bleomycin. Furthermore, we review therapeutic targets and possible promising strategies for ameliorating bleomycin-induced lung injury.

Formulation of quinoa oil-alginate loaded nanoemulsion and its anticancer efficacy as a therapy for chemically induced breast cancer.

BACKGROUND: Quinoa seeds (Chenopodium quinoa Willd.) have gained interest due to their naturally occurring phytochemicals and antioxidants. They possess potent anticancer properties against human colorectal cancer. METHODS AND RESULTS: Fatty acids in quinoa oil were studied using gas chromatography-mass spectrometry. Rats were used to test the acute oral toxicity of the nanoemulsion loaded with sodium alginate. The DPPH radical scavenging method was employed to assess the nanoemulsion's ability to scavenge free radicals. It was examined the in vivo anticancer potential of quinoa oil nanoemulsion on rats with breast cancer induced by 7, 12-dimethylbenz (a) anthracene (DMBA). DMBA-breast cancer models received daily quinoa oil nanoemulsions for 30 days. The anticancer effect of the nanoemulsion was assessed by measuring ROS, protein carbonyl, gene expression of anti-oncogenes, and histopathological analysis. Supplying quinoa oil nanoemulsion significantly reduced the increase in serum ROS and PC levels induced in breast cancer tissue. The expression levels of antioncogenes in breast cancer tissue were decreased by the quinoa oil nanoemulsion. Nanoemulsions also improved the cellular morphology of breast tumors. CONCLUSION: The study results indicate that quinoa oil nanoemulsion has anticancer activity against breast cancer, effectively modulating oxidative stress markers, anti-oncogene expressions, and tissue architecture. It can be inferred from the results that quinoa oil nanoemulsion is a chemoprotective medication that may hinder breast cancer progression in rats.

Synthesis of eco-friendly layered double hydroxide and nanoemulsion for jasmine and peppermint oils and their larvicidal activities against Culex pipiens Linnaeus.

Mosquito-borne diseases represent a growing health challenge over time. Numerous potential phytochemicals are target-specific, biodegradable, and eco-friendly. The larvicidal activity of essential oils, a jasmine blend consisting of Jasmine oil and Azores jasmine (AJ) (Jasminum sambac and Jasminum azoricum) and peppermint (PP) Mentha arvensis and their nanoformulations against 2nd and 4th instar larvae of Culex pipiens, was evaluated after subjecting to different concentrations (62.5, 125, 250, 500, 1000, and 2000 ppm). Two forms of phase-different nanodelivery systems of layered double hydroxide LDH and oil/water nanoemulsions were formulated. The synthesized nanoemulsions showed particle sizes of 199 and 333 nm for AJ-NE and PP-NE, with a polydispersity index of 0.249 and 0.198, respectively. Chemical and physiochemical analysis of TEM, SEM, XRD, zeta potential, drug loading capacity, and drug release measurements were done to confirm the synthesis and loading efficiencies of essential oils' active ingredients. At high concentrations of AJ and PP nanoemulsions (2000 ppm), O/W nanoemulsions showed higher larval mortality than both LDH conjugates and crude oils. The mortality rate reached 100% for 2nd and 4th instar larvae. The relative toxicities revealed that PP nanoemulsion (MA-NE) was the most effective larvicide, followed by AJ nanoemulsion (AJ-NE). There was a significant increase in defensive enzymes, phenoloxidase, and α and ß-esterase enzymes in the treated groups. After treatment of L4 with AJ, AJ-NE, PP, and PP-NE, the levels of phenoloxidase were 545.67, 731.00, 700.00, and 799.67 u/mg, respectively, compared with control 669.67 u/mg. The activity levels of α-esterase were 9.71, 10.32, 8.91, and 10.55 mg α-naphthol/min/mg protein, respectively. It could be concluded that the AJ-NE and PP-NE nanoformulations have promising larvicidal activity and could act as safe and effective alternatives to chemical insecticides.

Social media addiction and depression and their predictors among university students.

OBJECTIVES: Social media facilitate the interaction between individuals without regard to the distances between the users. Everybody who has access to internet can suffer from social media addiction. During COVID-19 pandemic there was an increase in social media usage among all population types and especially the university students, which would negatively affect their mental health. Therefore, this study aims at assessing social media addiction and depression among pharmacy students by using questionnaires specifically designed for this purpose. METHODS: A cross-sectional study with convenience sampling was conducted from the start of November to the end of December 2021 among undergraduate pharmacy students in Mosul city, Iraq. An online questionnaire was adopted; it consisted of three parts, the first was for collecting socio-demographic and social media usage information, Social Media Addiction Questionnaire (SMAQ) was used in the second part to assess social media addiction of the participants, and the third part was comprised of the Patient Health Questionnaire (PHQ-9) to assess depression among students. RESULTS: Six hundred-three students completed the questionnaire and constituted the final study sample. Instagram was the most used social media program among the students. About 38 % of the students were at risk of becoming addicted on social media, with only 8.4 % of them being minimally or not depressed. Additionally, positive significant correlation was observed between social media addiction and depression. Using social media for more than 4 h and poor academic performance were found to be predictors for social media addiction and depression. CONCLUSIONS: Addiction to social media and depression are prevalent among pharmacy students in Iraq and the two are related to each other.

Clinical and paraclinical predictors of early neurological deterioration and poor outcome in spontaneous intracerebral hemorrhage.

Background: Spontaneous intracerebral hemorrhage (sICH) is the second most common form of stroke. It is a major cause of morbidity and mortality. Several clinical and radiological parameters are related to its poor outcome. The aim of this study is to elucidate the clinical, laboratory, and radiological factors associated with early neurological deterioration and poor outcome in patients with ICH. Results: seventy patients diagnosed with sICH were evaluated within the first 72 h from the onset of symptoms by Clinical, radiological, and laboratory parameters. Patients were assessed for early neurological deterioration (END) during the hospital stay (up to 7 days from admission) using Glasgow coma scale (GSC), and the National Institutes of Health Stroke Scale (NIHSS), and within 3 months from stroke onset using modified Rankin scale (mRS). ICH score and Functional Outcome in Patients with Primary Intracerebral Hemorrhage (FUNC) Score were calculated for prognostication. 27.1% and 71.42% of patients had END and showed unfavorable outcome, respectively. Clinical indices, as NIHSS > 7 on admission and age > 51 years, radiological characteristics, as large hematoma size, leukoaraiosis, and mass effect detected on CT scan, as well as serum biomarkers; serum urea level > 50 mg/dL, high neutrophil:lymphocyte ratio on admission, high ALT and AST, as well as low total, LDL, and HDL cholesterol levels, all were significantly associated with poor outcome in the patients. Stepwise multivariate logistic regression analysis found the presence of aspiration to be an independent predictor of END, and the scores of NIHSS > 7 on admission, age > 51 years, and urea level > 50 mg/dL were independent predictors of poor outcome. Conclusions: There are several predictors for END as well as poor outcome in ICH. Some are clinical, others are radiological and laboratory. Aspiration was an independent predictor of END during hospital stay (3-7 days) in patients with ICH, while older age, high NIHSS and urea level on admission were independent predictors of poor outcome.

Co-application of entomopathogenic fungi with chemical insecticides against Culex pipiens.

Culex pipiens (Diptera: Culicidae) is a vector of many human and animal diseases. Its control is regarded as a preventative approach that is focused on effectively managing such diseases. In this context, dose response assays of two insecticides, bendiocarb and diflubenzuron were performed with two entomopathogenic fungi, Beauveria bassiana and Metarhizium anisopliae against 3rd instar C. pipiens larvae. The most effective agents, combination experiments as well as enzymatic activities of phenoloxidase (PO) and chitinase (CHI) were also assessed. The results showed that diflubenzuron was more effective at low concentrations (LC50: 0.001 ppm) than bendiocarb (LC50: 0.174 ppm), whereas M. anisopliae was more effective (LC50: 5.2 × 105 conidia/mL) than B. bassiana (LC50: 7.5 × 107 conidia/mL). Synergistic interactions were observed when diflubenzuron was applied at 2- and 4-days post- exposure to M. anisopliae, with the highest degree of synergism observed when diflubenzuron was applied 2 days post-fungal exposure (χ2 = 5.77). In contrast, additive interactions were recorded with all other insecticide-fungal combinations. PO activities significantly (p ≤ 0.05) increased during 24 h after a single diflubenzuron treatment as well as when diflubenzuron was applied prior to M. anisopliae, whereas suppressed after 24 h when M. anisopliae applied prior to diflubenzuron as well as after 48 h from single and combined treatments. CHI activity increased 24 h after both single and combined treatments, the activity remained elevated 48 h after a single diflubenzuron treatment and when diflubenzuron was applied after M. anisopliae. Histological study of the cuticle by transmission electron microscopy revealed abnormalities following single and combined treatments. Germination of the conidia and production of the mycelium that colonizes the lysing cuticle was obvious when diflubenzuron was applied 48 h after M. anisopliae exposure. Overall, these results demonstrate that M. anisopliae is compatible with diflubenzuron at lower concentrations and that combined applications can improve C. pipiens management.

Acaricide resistance and novel photosensitizing approach as alternative acaricides against the camel tick, Hyalomma dromedarii.

The control of the camel tick, Hyalomma dromedarii is very crucial. This study evaluated the novel toxicity of photosensitizers and Phoxim insecticide against H. dromedarii males using the adult immersion tests. Ticks were subjected to sunlight for 10 min post-treatment (PT). The optical characters of the applied materials were determined by UV-Vis spectroscopy (250-900 nm wavelengths). The intensity of spectra decreased as dye concentration decreased. The optical bandgap energies of the dyes at different concentrations were not changed as the concentration changed and decreased as the absorption peak of individual dyes red-shifted. The mortalities 72 h PT reached 42.2%, 44.4%, 51.1%, 71.1%, 46.7%, 48.9%, 44.4%, and 55.6% for chlorophyllin, echinochrome, field stain, methylene blue, phthalocyanine, rhodamine 6G, riboflavin, and safranin, respectively. Methylene blue recorded the highest median lethal concentration (LC50 = 127 ppm) followed by safranin, field stain, rhodamine 6G, phthalocyanine, echinochrome riboflavin, and chlorophyllin (LC50 = 209, 251, 271, 303, 324, 332, and 362 ppm, respectively, 72 h PT). Their median lethal time, LT50, values PT with 240 ppm were 45, 87, 96, 72, 129, 115, 131, and 137 h, respectively. The relative toxicities of the LC50 values 72 h PT showed that chlorophyllin, echinochrome, field stain, methylene blue, phthalocyanine, rhodamine 6G, riboflavin, and safranin were 3.2, 3.6, 4.6, 9.1, 3.8, 4.3, 3.5, and 5.6 times, respectively, more effective than Phoxim. Methylene blue, safranin, and field stain showed a broad absorbance area indicating a large photoactivity and better phototoxicity and could be used as alternative agents to synthetic acaricides.

The suppressive role of nanoencapsulated chia oil against DMBA-induced breast cancer through oxidative stress repression and tumor genes expression modulation in rats.

BACKGROUND: Chia oil is high in omega-3 fatty acids, which have been linked to a lower risk of many diseases, including cancer. Oil encapsulation is a method that holds promise for maintaining oil content while enhancing solubility and stability. The purpose of this study is to prepare nanoencapsulated Chia oil and investigate its suppressive effects on rat chemically induced breast cancer. METHODS: The oil was extracted from commercial Chia seeds and their fatty acids were analyzed using Gas Chromatography-mass spectrometry (GC/MS). Sodium alginate was used as a loading agent to create the Chia oil nanocapsules. The DPPH assay was used to assess the oil nanocapsules' capacity to scavenge free radicals. Breast cancer induction was done by single dose subcutaneously administration of 80 mg/kg dimethylbenz (a) anthracene (DMBA). Models of breast cancer were given Chia oil nanocapsules orally for one month at doses of 100 and 200 mg/kg. Through measuring intracellular reactive oxygen species (ROS) and protein carbonyl, assessing the gene expression of tumor suppressor genes (BRCA 1 & 2, TP53), and conducting histopathological analysis, the suppressive effect of Chia oil nanocapsules was examined. RESULTS: The increase in ROS and PC levels brought on by DMBA was significantly decreased by the administration of Chia oil nanocapsules. In tumor tissue from rats given Chia oil nanocapsules, the mRNA expression levels of BRCA1, BRCA2, and TP53 were controlled Histopathological analysis clarified that the tissue architecture of breast tumors was improved by nanocapsules management. CONCLUSIONS: These findings demonstrate the ability of Chia oil nanocapsules to inhibit cancer cells in the rat breast.

Find new channel for overcoming chemoresistance in cancers: Role of stem cells-derived exosomal microRNAs.

Chemoresistance has remained a significant concern in tumor recurrence and elevated cancer-related mortalities. A deep insight into mechanisms by which cancerous cells resist administered drugs can pave the way to overcome chemotherapy-induced cell death and develop novel procedures to rescue patients. Regarding accumulated data, stem cell-derived exosomal microRNAs (miRNAs) can be deemed a novel and promising method to overcome chemoresistance. It seems exosomal miRNAs play a dual role in the cancer microenvironment. On the one hand, as a messenger, they are transferred between donor and recipient cells contributing to cancer chemoresistance. On the other hand, stem cell-derived exosomal miRNA significantly restrains tumorigenesis and inhibits or alleviates drug resistance in the tumor niche. Hence, our purpose in this review evaluating the roles of stem cells-derived exosomal microRNAs in overcoming chemoresistance in tumors.

Impact of Intra-Articular Local Anesthesia Infiltration versus Femoral Nerve Block for Postoperative Pain Management in Total Knee Arthroplasty.

Background: Postoperative pain relief after total knee arthroplasty (TKA) can be attained by using several techniques such as intravenous analgesia, epidural analgesia, and peripheral nerve blocks that include femoral nerve and saphenous nerve. Several authors recommended intra-articular injection of local anesthetic (IALA) as a part of multimodal analgesia regimens for TKA instead of other techniques. Aims: The present study compares IALA technique efficacy with single-shot femoral nerve block (FNB) as part of multimodal analgesia regimen in TKA patients for postoperative pain management. Setting and Design: Perioperative care, randomized double-blind comparative study. Subjects and Methods: We recruited a total of 60 patients scheduled for unilateral total knee replacement under spinal anesthesia. Subjects were allocated randomly into two groups FNB and IALA receiving ultrasound-guided FNB and Intra-articular local anesthesia and morphine mix infiltration, respectively. Twenty-four hour postoperative morphine consumption through patient-controlled analgesia was the primary outcome measure in our study. Secondary outcome measures were pain scores, nausea and vomiting. Statistical Analysis: Chi-square test, Mann-Whitney test. Results: The amount of morphine consumed at the end of 24 h was noted to be higher in IALA group as compared to FNB (FNB - 16.03 ± 9.37 mgs; IALA - 23.60 ± 13.73 mgs P = 0.03). Visual analog score at 24 h with knee flexion was better in FNB group (FNB - 1.27 ± 1.43; IALA 2.42 ± 2.54, P = 0.04). Conclusion: FNB technique provides better analgesia in comparison to IALA for postoperative pain management in terms of PCA morphine consumption.

Fish Oil and Primrose Oil Suppress the Progression of Alzheimer's Like Disease Induced by Aluminum in Rats.

The role of fish oil, primrose oil and their mixture in ameliorating the changes in Alzheimer's like model was evaluated in rats. Primrose oil and primrose/fish oil mixture fatty acids composition was assessed by gas chromatography. The rat experiment consisted of 5 groups; the first fed on balanced diet as control normal (CN); the other four groups treated with intraperitoneal aluminum lactate and consumed dyslipidemic diet; one group served as control Alzheimer's like disease (CA) while the other three groups (test groups) received daily oral dose from primrose oil, fish oil and primrose/fish oil mixture separately for 5 weeks. Results showed primrose oil and primrose/ fish oil mixture to contain gamma linolenic acid as 9.15 and 4.3% of total fatty acids, respectively. Eicosapentaenoic and docosahexaenoic were present as 10.9 and 6.5 %, respectively in the oil mixture. Dyslipidemia and increased erythrocyte sedimentation rate (ESR), plasma butyrylcholinesterase (BChE), brain malondialdehyde (MDA) and NO with decrease in plasma magnesium, brain catalase, reduced glutathione, body weight gain and brain weight were demonstrated in CA compared to CN. Brain histopathology and immuno-histochemistry showed neuronal degeneration and neurofibrillary tangles with elevated myeloperoxidase and nuclear factor-kappa B in CA compared to CN. The tested oils demonstrated neuro-protection reflected in the variable significant improvement of biochemical parameters, immuno-histochemistry and brain histopathology. Primrose/fish oil mixture was superior in reducing ESR, brain MDA, plasma activity of BChE and brain histopathological changes along with elevating plasma magnesium. Primrose/fish oil mixture and fish oil were more promising in improving plasma high density lipoprotein cholesterol (HDL-C) than primrose. Fish oil was the most efficient in improving plasma total cholesterol (T-C), low density lipoprotein cholesterol and T-C /HDL-C. Primrose/fish oil mixture and primrose oil were superior in elevating brain catalase compared to fish oil. Other parameters were equally improved by the different oil treatments. Primrose oil, fish oil and their mixture reduced the progression of Alzheimer's disease in rats with superiority to primrose/fish oil mixture.

Functional Foods for Management of Diarrhea and Malnutrition in Rats Emphasizing on Nucleotides Role.

BACKGROUND: Diarrhea and malnutrition are major health problems in developing countries. Inflammation, high oxidative stress, poor nutritional status, and fatty liver were encountered during such diseases. Patents for diarrhea and malnutrition management (WO2007/130882A2, WO00/37106A1, WO2014/152420, and CA2987364A1) were published. OBJECTIVE: The objective was to introduce anti-diarrhea functional foods with a preventive effect on malnutrition. METHODS: Two processing techniques were applied for preparing functional foods (formula 1 ingredients were made into cookies followed by grinding; formula 2 ingredients were pre-cooked, dried, and mixed in powder form) that were evaluated in a rat model of diarrhea with malnutrition (DM). Formula 2 was also assessed when mixed with nucleotides. The ingredients were edible plants that possess an anti-diarrheal effect with high protein sources (legumes and casein). RESULTS: Induction of diarrhea with malnutrition, high oxidative stress, inflammation, accumulation of liver fat, and histopathological changes were demonstrated in DM control compared to normal control. The functional foods produced variable improvement in growth curves, food efficiency ratio, hemoglobin, hematocrit and plasma zinc, protein, albumin, globulin, lipase activity, and MDA. Formula 1 was superior in improving intestinal histopathology while formula 2 was more efficient in elevating plasma iron. Formula 2 with nucleotides was the best in improving growth curves, alkaline phosphatase, and reducing liver fat. Intestinal mucosa reduced glutathione and nitrite showed an efficient significant reduction on treatment with formula 2 with or without nucleotides. The formulas showed an anti-diarrheal effect by improving feces weight and moisture content. CONCLUSION: Studied functional foods showed an anti-diarrheal effect and malnutrition improvement with different degrees.

Role of Probiotic Mixture with and Without Green Tea Extract in Prevention of Hepatorenal Syndrome in Rat Model.

BACKGROUND AND OBJECTIVE: Hepatorenal syndrome (HRS) is a major public health problem in which both liver and kidney dysfunctions are encountered. The present research aimed to investigate the beneficial use of micro-encapsulated probiotic alone (Bifidobacterium bifidum, Lactobacillus delbrueckii and Streptococcus thermophilus mixture) or with green tea alcohol extract in HRS model in rats. MATERIALS AND METHODS: Flavonoids content and in vitro antioxidant activity of the extract were assessed. The animal experiment consisted of 4 groups; control healthy, control with HRS and two test groups with HRS and treated with either the encapsulated probiotic mixture alone or with green tea extract. After 3 weeks; urinary creatinine was determined in 24 h rat urine samples. Colonic microbiota was assessed in faeces. Plasma malondialdehyde, nitrite, C-reactive protein, creatinine, uric acid, urea and the activity of transaminases, catalase (CAT) and angiotensin-1 converting enzyme (ACE-1) were determined with calculation of creatinine clearance. RESULTS: Results showed significant increase in all biochemical parameters of HRS control except for ACE-1, CAT and creatinine clearance that experienced significant reduction along with dysbiosis compared to healthy control. Test groups showed improvement in all biochemical parameters with superiority to probiotic-green tea extract combination. Both treatments produced significant increase in fecal B. bifidum, S. thermophilus and L. bulgaricus and reduction of Staphylococci and Coliform. The effect of probiotic-green tea extract combination was more pronounced concerning the last three. Flavonoids and antioxidant activity of the extract were 1.325±0.01 mg quercetin/g and 98±1.66%, respectively. CONCLUSION: Administration of micro-encapsulated probiotic with or without alcohol green tea extract exerted significant prevention of HRS in rat with superiority to probiotic-green tea extract combination.