Role of nutraceutical against exposure to pesticide residues: power of bioactive compounds.

Pesticides play a crucial role in modern agriculture, aiding in the protection of crops from pests and diseases. However, their indiscriminate use has raised concerns about their potential adverse effects on human health and the environment. Pesticide residues in food and water supplies are a serious health hazards to the general public since long-term exposure can cause cancer, endocrine disruption, and neurotoxicity, among other health problems. In response to these concerns, researchers and health professionals have been exploring alternative approaches to mitigate the toxic effects of pesticide residues. Bioactive substances called nutraceuticals that come from whole foods including fruits, vegetables, herbs, and spices have drawn interest because of their ability to mitigate the negative effects of pesticide residues. These substances, which include minerals, vitamins, antioxidants, and polyphenols, have a variety of biological actions that may assist in the body's detoxification and healing of harm from pesticide exposure. In this context, this review aims to explore the potential of nutraceutical interventions as a promising strategy to mitigate the toxic effects of pesticide residues.

Bone morphogenetic protein 1: a prognostic indicator and potential biomarker in three cancer types.

BACKGROUND: Bone morphogenetic protein 1 (BMP1) is a metalloprotease that plays a role in activating both transforming growth factor-ß (TGF-ß) and BMP signaling pathways. TGF-ß has been identified as a factor initiating and facilitating cancer development. Consequently, we propose the hypothesis that dysregulation of BMP1 could potentially contribute to the onset and advancement of human cancers. METHODS: In this research, we aimed to analyze BMP1 expression level and the associated clinical outcomes across various cancers using online cancer OMICS databases, advanced Bioinformatics tools, and molecular analyses. RESULTS: The outcomes of our web server-based expression analysis indicated an up-regulation of BMP1 in a majority of the human cancers examined. External validation using clinical samples also showed higher expression of BMP1. Moreover, heightened BMP1 expression exhibited a noteworthy correlation with reduced overall survival (OS) duration in Bladder Cancer (BLCA), Kidney Renal Clear Cell Carcinoma (KIRC), and Lung Adenocarcinoma (LUAD) patients. This suggests a substantial involvement of the BMP1 gene in the development and progression of these three types of cancers. The major signaling pathways related with BMP1 enriched genes were "ECM-receptor interaction, Amoebiasis, Focal adhesion, Protein digestion and absorption, progesterone-mediated, PI3K-Akt signaling pathway, and platelet activation". Moreover, we also explored some interesting correlations among BMP1 expression and its DNA promoter methylation level, CD8+ T immune cells level, and genetic variations. CONCLUSION: In conclusion, our study has provided some solid basis for BMP1 to be used as a reliable common biomarker for BLCA, KIRC, and LUAD patients.

Sustainable Nanoparticles from Stephania glabra and Analysis of Their Anticancer Potential on 2D and 3D Models of Prostate Cancer.

In pursuit of a novel effective treatment for prostate cancer, methanolic extract of Stephania glabra tubers (Sg-ME) was utilized to fabricate silver (Sg-AgNP), copper oxide (Sg-CuONP), and silver-copper bimetallic nanoparticles (Sg-BNP). The characterization of the nanoparticles confirmed spherical shape with average diameters of 30.72, 32.19, and 25.59 nm of Sg-AgNP, Sg-CuONP, and Sg-BNP, respectively. Interestingly, these nanoparticles exhibited significant cytotoxicity toward the prostate cancer (PC3) cell line while being non-toxic toward normal cells. The nanoparticles were capable of inducing apoptosis in PC3 cells by enhancing reactive oxygen species (ROS) generation and mitochondrial depolarization. Furthermore, the shrinkage of 3D prostate tumor spheroids was observed after 4 days of treatment with these green nanoparticles. The 3D model system was less susceptible to nanoparticles as compared to the 2D model system. Sg-BNP showed the highest anticancer potential on 2D and 3D prostate cancer models.

The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain.

Methamphetamine, a highly addictive central nervous system (CNS) stimulant, is used worldwide as an anorexiant and attention enhancer. Methamphetamine use during pregnancy, even at therapeutic doses, may harm fetal development. Here, we examined whether exposure to methamphetamine affects the morphogenesis and diversity of ventral midbrain dopaminergic neurons (VMDNs). The effects of methamphetamine on morphogenesis, viability, the release of mediator chemicals (such as ATP), and the expression of genes involved in neurogenesis were evaluated using VMDNs isolated from the embryos of timed-mated mice on embryonic day 12.5. We demonstrated that methamphetamine (10 µM; equivalent to its therapeutic dose) did not affect the viability and morphogenesis of VMDNs, but it reduced the ATP release negligibly. It significantly downregulated Lmx1a, En1, Pitx3, Th, Chl1, Dat, and Drd1 but did not affect Nurr1 or Bdnf expression. Our results illustrate that methamphetamine could impair VMDN differentiation by altering the expression of important neurogenesis-related genes. Overall, this study suggests that methamphetamine use may impair VMDNs in the fetus if taken during pregnancy. Therefore, it is essential to exercise strict caution for its use in expectant mothers.

Role of polycystic ovarian syndrome in developing psychological burden in Saudi Arabian females: A case control study.

It is well known that polycystic ovarian syndrome (PCOS) may elevate psychological problems in patients, but there is a scarcity of the studies among Saudi Arabian population. This research was designed to investigate the influence of PCOS on the development of psychological load in terms of depression, anxiety, and stress in comparison to normal women who have no PCOS. Further, a correlation of psychological distress in PCOS females was done with their educational level. This is case-control research carried out in one of Riyadh's multispecialty hospitals. In the PCOS patients and control groups (each with 84 samples), samples were collected using convenience sampling and a simple random approach, respectively. The psychological burden was determined using DASS-21. The data obtained were analyzed using SPSS-IBM 25. Most participants (52.9%) were between the ages of 26 and 35 and had a university education (68.4%). A significantly higher percentage of PCOS patients (P = 0.001) had irregular menses, hirsutism, infertility, and acne in comparison to the mothers without PCOS. There was a significantly higher possibility of depression (P = 0.003), anxiety (P = 0.016), and stress (P = 0.001) among PCOS patients than in control subjects. Among the psychological domain tested in the study, the risk of developing stress (odds ratio, OR = 8.32) was high when compared to depression (OR = 3.12) and anxiety (OR = 2.127) in PCOS patients. Furthermore, when compared to PCOS females with less education, a significantly lower number of university-educated PCOS females developed depression. The study demonstrates a high prevalence of psychological burden among the PCOS population. Higher education has been shown to help in alleviating depression in PCOS females. Meeting PCOS women's psychological needs will improve their overall health status.

The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos.

The effects of second-generation antipsychotics on prenatal neurodevelopment, apoptotic neurodegeneration, and postnatal developmental delays have been poorly investigated. Even at standard doses, the use of quetiapine fumarate (QEPF) in pregnant women might be detrimental to fetal development. We used primary mouse embryonic neurons to evaluate the disruption of morphogenesis and differentiation of ventral midbrain (VM) neurons after exposure to QEPF. The dopaminergic VM neurons were deliberately targeted due to their roles in cognition, motor activity, and behavior. The results revealed that exposure to QEPF during early brain development decreased the effects of the dopaminergic lineage-related genes Tyrosine hydroxylase(Th), Dopamine receptor D1 (Drd1), Dopamine transporter (Dat), LIM homeobox transcription factor 1 alfa (Lmx1a), and Cell adhesion molecule L1 (Chl1), and the senescent dopaminergic gene Pituitary homeobox 3 (Pitx3). In contrast, Brain derived neurotrophic factor (Bdnf) and Nuclear receptor-related 1 (Nurr1) expressions were significantly upregulated. Interestingly, QEPF had variable effects on the development of non-dopaminergic neurons in VM. An optimal dose of QEPF (10 µM) was found to insignificantly affect the viability of neurons isolated from the VM. It also instigated a non-significant reduction in adenosine triphosphate formation in these neuronal populations. Exposure to QEPF during the early stages of brain development could also hinder the formation of VM and their structural phenotypes. These findings could aid therapeutic decision-making when prescribing 2nd generation antipsychotics in pregnant populations.

Antidepressant Effect of Crocin in Mice with Chronic Mild Stress.

This study aimed to investigate the antidepressant property of crocin (Crocetin digentiobiose ester) using a chronic mild stress (CMS)-induced depression model in experimental mice. The tail suspension test (TST) and the sucrose preference test were used to evaluate the antidepressant effect on albino mice of either sex after three weeks of CMS. The period of immobility in the TST and percentage preference for sucrose solution were recorded. By monitoring brain malondialdehyde (MDA) level, catalase (CAT) activity, and reduced glutathione (GSH) level, the antioxidant potential was assessed. Three dosages of crocin (4.84, 9.69, and 19.38 mg/kg) were evaluated. When compared to controls, animals that received crocin administration during three periods of CMS had considerably shorter immobility times during the TST. Crocin treatment also raised the percentage preference for sucrose solution in a dose-dependent manner, bringing it to parity with the conventional antidepressant, imipramine. Animals that received a high dose of crocin had a much greater spontaneous locomotor activity. Furthermore, a high dose of crocin remarkably lowered plasma corticosterone and nitrite levels brought on by CMS. Additionally, high doses of crocin given during CMS greatly enhanced reduced glutathione levels while considerably reducing the brain's MDA and catalase activities. In conclusion, high doses of crocin may have an antidepressant effect in an animal model through several mechanisms. However, further studies should be carried out to explore the role of neurotransmitters for their antidepressant property.

Synthesis and Characterization of Tetracycline Loaded Methionine-Coated NiFe2O4 Nanoparticles for Anticancer and Antibacterial Applications.

In the present study, nickel ferrite (NiFe2O4)-based smart magnetic nanoparticles were fabricated and coated with methionine. Physiochemical characterization of the obtained Met-NiFe2O4 nanoparticles revealed the presence of methionine coating over the nanoparticle surface. Drug release study indicated that Tet-Met-NiFe2O4 nanoparticles possess pH-responsive controlled drug release behavior for tetracycline (Tet). The drug loading content for Tet was found to be 0.27 mg/L of nanoparticles. In vitro cytotoxicity test showed that the Met-NiFe2O4 nanoparticles is biocompatible. Moreover, this magnetic nanostructured material shown strong anticancer property as these nanomaterials significantly reduced the viability of A375 cells when compared to free Tet solution. In addition, Tet-Met-NiFe2O4 nanoparticles also showed strong antibacterial activity against different bacterial pathogens.

A Parkinson's disease model composed of 3D bioprinted dopaminergic neurons within a biomimetic peptide scaffold.

Parkinson's disease (PD) is a progressive neurological disorder that affects movement. It is associated with lost dopaminergic (DA) neurons in thesubstantia nigra, a process that is not yet fully understood. To understand this deleterious disorder, there is an immense need to develop efficientin vitrothree-dimensional (3D) models that can recapitulate complex organs such as the brain. However, due to the complexity of neurons, selecting suitable biomaterials to accommodate them is challenging. Here, we report on the fabrication of functional DA neuronal 3D models using ultrashort self-assembling tetrapeptide scaffolds. Our peptide-based models demonstrate biocompatibility both for primary mouse embryonic DA neurons and for human DA neurons derived from human embryonic stem cells. DA neurons encapsulated in these scaffolds responded to 6-hydroxydopamine, a neurotoxin that selectively induces loss of DA neurons. Using multi-electrode arrays, we recorded spontaneous activity in DA neurons encapsulated within these 3D peptide scaffolds for more than 1 month without decrease of signal intensity. Additionally, vascularization of our 3D models in a co-culture with endothelial cells greatly promoted neurite outgrowth, leading to denser network formation. This increase of neuronal networks through vascularization was observed for both primary mouse DA and cortical neurons. Furthermore, we present a 3D bioprinted model of DA neurons inspired by the mouse brain and created with an extrusion-based 3D robotic bioprinting system that was developed during previous studies and is optimized with time-dependent pulsing by microfluidic pumps. We employed a hybrid fabrication strategy that relies on an external mold of the mouse brain construct that complements the shape and size of the desired bioprinted model to offer better support during printing. We hope that our 3D model provides a platform for studies of the pathogenesis of PD and other neurodegenerative disorders that may lead to better understanding and more efficient treatment strategies.

Characterization of Phytochemicals, Nutrients, and Antiradical Potential in Slim Amaranth.

Slim amaranth (A. hybridus) having a C4 photosynthetic pathway with diverse variability is a climate-resilient crop that tolerates abiotic stresses. Owing to the high productivity of the C4 pathway, we have been searching for suitable accessions as preferable high-yielding antioxidant-enriched cultivars with ample bioactive compounds, or for future breeding programs to improve bioactive compounds as a source of natural antioxidants. Twelve slim amaranth accessions were tested for nutraceuticals, phytopigments, radical scavenging capacity (two different assays), vitamins, total flavonoids, and total polyphenols content. Slim amaranth leaves contained ample dietary fiber, protein, moisture, and carbohydrates. The current investigation demonstrated that there was remarkable K, Ca, Mg (8.86, 26.12, and 29.31), Fe, Mn, Cu, Zn, (1192.22, 275.42, 26.13, and 1069.93), TP, TF (201.36 and 135.70), pigments, such as chlorophyll a, ab, and b, (26.28, 38.02, and 11.72), betalains, betaxanthins, betacyanins (78.90, 39.36, 39.53,), vitamin C (1293.65), ß-carotene, total carotenoids, (1242.25, 1641.07), and TA (DPPH, ABTS+) (27.58, 50.55) in slim amaranth leaves. The widespread variations were observed across the studied accessions. The slim amaranth accessions, AH11, AH10, and AH12, exhibited high profiles of antioxidants including high potentiality to quench radicals and can be selected as preferable high-yielding antioxidant-enriched cultivars with ample bioactive compounds. Phytopigments, flavonoids, vitamins, and phenolics of slim amaranth leaves showed intense activity of antioxidants. Slim amaranth could be a potential source of proximate phenolics, minerals, phytopigments, vitamins, and flavonoids for gaining adequate nutraceuticals, bioactive components, and potent antioxidants. Moderate yielding accessions having moderate phytochemicals can be used to develop new high-yielding antioxidant-enriched cultivars for future breeding programs to improve bioactive compounds as a source of natural antioxidants.

Ameliorative impacts of chrysin against gibberellic acid-induced liver and kidney damage through the regulation of antioxidants, oxidative stress, inflammatory cytokines, and apoptosis biomarkers.

Gibberellic acid (GA3), a widely known plant growth regulator, has been mostly used in agriculture. Little is known regarding its toxicity or the impact of its metabolic mechanism on human health. The current study examined the protective impact of chrysin against GA3-induced liver and kidney dysfunctions at biochemical, molecular, and histopathological levels. Forty male albino rats were allocated into 4 groups. The control group received saline; the chrysin group received 50 mg/kg/BW orally daily for 4 weeks; the GA3 group received 55 mg/kg/BW GA3 via daily oral gavage for 4 weeks, and the protective group (chrysin + GA3) was administered both chrysin and GA3 at the same dosage given in chrysin and GA3 groups. Chrysin was administered 1 h earlier than GA3. The GA3 induced liver and kidney injuries as proven by the elevation of hepatic and renal markers with a significant increase in malondialdehyde levels. Furthermore, a decrease of catalase and glutathione was reported in the GA3-administered rats. Pre-administration of chrysin significantly protected the hepatorenal tissue against the deleterious effects of GA3. Chrysin restored the hepatorenal functions and their antioxidant ability to normal levels. Moreover, chrysin modulated the hepatorenal toxic effects of GA3 at the molecular level via the upregulation of the antiapoptotic genes, interleukin-10 (IL-10), hemoxygenase-1, and nuclear factor erythroid 2-related factor 2 expressions; the downregulation of the kidney injury molecule-1 and caspase-3 mRNA expressions; and a decrease in IL-1ß and tumor necrosis factor-α secretions. Additionally, the pre-administration of chrysin effectively attenuated the GA3-induced hepatorenal histopathological changes by regulating the immunoexpression of cytochrome P450 2E1 (CYP2E1) and pregnane X receptor, resulting in normal values at the cellular level. In conclusion, chrysin attenuated GA3-induced oxidative hepatorenal injury by inhibiting free-radical production and cytokine expression as well as by modulating the antioxidant, apoptotic, and antiapoptotic activities. Chrysin is a potent hepatorenal protective agent to antagonize oxidative stress induced by GA3.

Recent developments in microbial degradation of polypropylene: Integrated approaches towards a sustainable environment.

Fossil-fuel-based plastics have many enticing properties, but their production has resulted in significant environmental issues that require immediate attention. Despite the fact that these polymers are manmade, some bacteria can degrade and metabolise them, suggesting that biotechnologies based on the principle of plastic biodegradation could be beneficial. Among different types of plastics, polypropylene (PP), either having low or high density, is one of the most consumed plastics (18.85%). Their debasement under natural conditions is somewhat tricky. Still, their debasement under natural conditions is rather difficult slightly. However, different scientists have still made efforts by employing other microbes such as bacteria, fungi, and guts bacteria of larvae of insects to bio-deteriorate the PP plastic. Pre-irradiation techniques (ultraviolet and gamma irradiations), compatibilizers, and bio-additives (natural fibers, starch, and polylactic acid) have been found to impact percent bio-deterioration of different PP derivatives stronglythe various. The fungal and bacterial study showed that PP macro/microplastic might serve as an energy source and sole carbon during bio-degradation. Generally, gravimetric method or physical characterization techniques such as FTIR, XRD, SEM, etc., are utilized to affirm the bio-degradation of PP plastics-based materials. However, these techniques are not enough to warrant the bio-deterioration of PP. In this regard, a new technique approach that measures the amount of carbon dioxide emitted during bacterial or fungus degradation has also been discussed. In addition, further exploration is needed on novel isolates from plastisphere environments, sub-atomic strategies to describe plastic-debasing microorganisms and improve enzymatic action strategies, and omics-based innovations to speed up plastic waste bio-deterioration.

Gibberellic acid-induced hepatorenal dysfunction and oxidative stress: Mitigation by quercetin through modulation of antioxidant, anti-inflammatory, and antiapoptotic activities.

The plant growth regulator gibberellic acid (GA3) is widely used in agriculture in many countries. However, little is known about its danger to human health or its physiologic and biochemical pathways. Our study examined the effect of GA3 on liver and kidney function and the effect of quercetin on the hepatorenal toxicity induced by GA3 in four groups of male albino rats. For 4 weeks, the control group (CNT) received saline, the quercetin group (QR) received daily intraperitoneal injections of quercetin (50 mg/kg/BW) dissolved in saline, the gibberellic acid group (GA3) received GA3 (55 mg/kg/BW) via oral gavage, and the protective group (QR) was injected with quercetin and gavaged with GA3 in the same doses used in the QR and GA3 groups (50 mg/kg/BW +GA3 and 55 mg/kg/BW). GA3 induced liver and kidney injury, as shown by elevated serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and gamma-glutamyl transferase (GPT, GOT, and GGT) as well as increased levels of creatinine, urea, and uric acid. Hepatorenal toxicity was demonstrated by a significant increase in levels of serum and tissue malondialdehyde (MDA) and decreased antioxidant enzyme activity, such as catalase (CAT) and superoxide dismutase (SOD), accompanied by a subsequent decrease in glutathione peroxidase (GPx) levels in liver and kidney tissue of GA3-treated rats. Administration of quercetin (QR) significantly protected hepatorenal tissue against the toxic effect of GA3 through normalization of the hepatic and renal function markers. It also retrieved the antioxidant ability by modulating the hepatorenal toxic effect at the molecular level through upregulation of antiapoptotic genes and downregulation of transforming growth factor-ß1 (TFG-ß1), cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB). Impairment of liver and kidney function was confirmed by histologic and immunohistochemical analyses. Pretreatment with quercetin was effective at attenuating histopathologic changes in hepatic and renal tissues by regulating the immunoexpression of caspase-3 and Bcl-2 to return them to more normal values. PRACTICAL APPLICATIONS: The confirmed hepatorenal dysfunction caused by GA3 was ameliorated by quercetin administration. Moreover, quercetin demonstrated the potential to reverse hepatorenal dysfunction by regulating inflammatory and antioxidant properties, inhibiting the production of free radicals and inflammation-associated cytokines, and modulating antioxidants and antiapoptotic activity.

Potential benefits of gallic acid as skeletal muscle relaxant in animal experimental models.

BACKGROUND AND OBJECTIVE: Many natural bioactive chemicals have been shown to have functional activity, suggesting that they could be useful in the treatment and management of a wide range of chronic conditions. Flavonoids, which include gallic acid (GA), are the most abundant polyphenols found in nature. Skeletal muscle relaxants are drugs that reduce undesired spasms while maintaining awareness and reflexes unaffected. The purpose of this investigation was to determine if GA has any skeletal muscle relaxant properties in experimental animal models. MATERIALS AND METHODS: The muscle relaxant activity of three dosages of GA (5, 10, and 20 mg/kg) was compared to that of normal diazepam (5 mg/kg) utilizing climbing, chimney, and modified Kondziela's inverted tests. An analysis of variance (ANOVA) and a post-ANOVA Tukey multiple comparisons test were used to assess the data. RESULTS: Animals given 10 and 20 mg/kg of GA had a great deal of trouble climbing up the chain, presumably because their muscles were relaxed. Similarly, rats given a high dose of GA (20 mg/kg) had a significantly (P < 0.05) longer response time in the chimney test, indicating a lack of attention and slowed muscle tone, resulting in problems with motor coordination. In inverted testing, animals given a high dose of GA had a significantly (P < 0.01) reduced holding capacity on the mesh for a longer period of time. A decrease in holding time is caused by a decrease in muscular contraction. The low dose of GA, on the other hand, failed to show muscle relaxant effect in any of the three models. CONCLUSIONS: As a conclusion, our data show that GA has a dose-dependent skeletal muscle relaxant effect when administered orally to mice.

The Potential Benefits of Using Garlic Oil and Its Active Constituent, Dially Disulphide, in Combination With Carvedilol in Ameliorating Isoprenaline-Induced Cardiac Damage in Rats.

Garlic oil and its primary component, diallyl disulphide (DADS), were tested in rats with isoprenaline (ISO) induced myocardial infarction for cardioprotective benefits when combined with carvedilol. Garlic oil (GO) was administered to rats (Sprague-dawley strain) at two doses of 50 and 100 mg/kg body weight, whereas DADS was given in two doses of 4.47 and 8.94 mg/kg, respectively. The animals were given oral doses of garlic oil and DADS on alternate days for 3 weeks, either alone or in combination with carvedilol (2 mg/kg). Cardiac injury was done by administering two doses of isoprenaline (150 mg/kg, sc) to all treated groups except the first, which served as a control. Biomarkers of cardiac injury and histological investigations were studied for their potential in reducing ISO-induced myocardial damage. Animals pretreated with GO, DADS, and carvedilol had significantly (p < 0.01) lowered heart weight and heart to body weight ratio. In rats treated with carvedilol plus high dosages of garlic oil (100 mg/kg, p.o) and DADS (8.94 mg/kg, p.o) compared to the ISO control and carvedilol group, the activities of SOD and Catalase were enhanced in cardiac tissue homogenate. When compared to ISO control and carvedilol group, the activities of LDH and CK-MB were elevated in heart tissue homogenate with a simultaneous reduction in their serum levels in animals treated with a combination of carvedilol with high doses of garlic oil (100 mg/kg, p.o) and DADS (8.94 mg/kg, p.o). Overall, combining garlic oil or DADS with carvedilol improved the cardioprotective effect of carvedilol and protected rats from ISO-induced myocardial infarction. However, more research is needed to establish the mechanism of garlic oil and DADS interaction with carvedilol.

The potential antioxidant bioactivity of date palm fruit against gentamicin-mediated hepato-renal injury in male albino rats.

Gentamicin (GM) is a commonly prescribed antimicrobial drug used for treatment of infections but associated hepatic and renal complications restrict its efficacy. Overproduction of free radicals and inflammation are involved in GM-induced hepato-renal damage. Date palm is renowned to have antioxidant and anti-inflammatory bioactive composites. In this context, the current research was purposed to assess the ameliorative influence of date palm extract (DE) supplementation against GM-induced hepato-renal injury. Gas chromatography-mass spectrometry (GC-MS) was used to detect the bioactive constitutes in DE. The protective action of high and low doses of DE was assessed alongside the GM remediation (80 mg/kg) in rats. GM evoked significant alterations in liver and kidney function biomarkers (aminotransferases, albumin, creatinine, and blood urea). Furthermore, notable elevations in malondialdehyde (MDA) level and increment expression of inducible nitric oxide synthase (iNOS) along with reduction in catalase (CAT) activity were observed in both organs after GM treatment. Oxidative stress was the main modulatory mechanism in GM-induced hepato-renal toxicity. However, DE could mitigate the GM-inflicted liver and kidney damage, in a dose-response pattern, due to its high content of phenolics and flavonoids.

Potential hepatoprotective effects of flavonoids contained in propolis from South Sulawesi against chemotherapy agents.

The use of doxorubicin and epirubicin as chemotherapy agent causes side effects such as liver damage due to oxidative stress by reactive oxygen species (ROS) that cause increased of ALT and AST level as liver parameter. One source of natural antioxidants as ROS neutralizer comes from flavonoid that contain in propolis. Most researchers claim that flavonoid can be used to protect the liver. The aim of this study was to test the hepatoprotective effect of flavonoid in propolis from South Sulawesi against doxorubicin and epirubicin. The experiment included male Sprague dawley rats divided into nine groups. The rats received the microcapsule propolis or the quercetin orally for 15 days. The hepatotoxicity was promoted by injection epirubicin and doxorubicin (i.v.) with a cumulative dose of 9 mg/kg. In this study, total polyphenol and flavonoid tests of propolis have been carried out, there were 1.1% polyphenols and 2.7% flavonoids, the antioxidant activity tests showed IC50 value of 9849 ppm and LCMS/MS tests supported the presence of phenolic compounds in propolis from South Sulawesi. Liver parameter was measured and the results showed that the propolis 200 mg/kg group produced the lowest ALT and had potential protective effect against doxorubicin and epirubicin-induced hepatotoxicity.

Cardioprotective Potential of Garlic Oil and Its Active Constituent, Diallyl Disulphide, in Presence of Carvedilol during Chronic Isoprenaline Injection-Mediated Myocardial Necrosis in Rats.

In isoprenaline (ISO)-induced myocardial infarcted rats, garlic oil (GO) and its main ingredient, diallyl disulfide (DADS), were examined for cardioprotective effects when used with carvedilol (CAR). GO, DADS and CAR were given to rats in their respective groups, either alone or together, with the addition of isoprenaline (3 mg/kg/day, subcutaneously) during the last 10 days of treatment. At the end of 14 days of treatment, blood samples were collected, the hearts were excised under anesthesia and weighed. Heart tissue homogenate was used to measure superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid reactive substances (TBARS). Furthermore, the serum activities of cardiac markers, including lactate dehydrogenase, creatine kinase, and cardiac troponin, were checked. Moreover, inflammatory markers including tumor necrosis factor alpha, interleukin one beta, interleukin six, and kappa bp65 subunit were assessed. Rats that received GO, DADS, and CAR exhibited a significant increase in the cardiac antioxidant enzyme activities with a simultaneous decrease in serum cardiac markers enzymes and inflammatory markers. The TBARS were significantly reduced in rats that received treatment. The addition of carvedilol to GO or DADS significantly elevated antioxidant activities and decreased the release of cardiac enzymes into blood circulation. Both DADS and GOl were almost similar in efficacy, indicating the potential role of DADS in garlic oil-mediated cardioprotection. Combining GO or DADS with CAR increased CAR's cardioprotective impact and protected rats from developing ISO-induced myocardial infarction.

RUNX1 mutation and elevated FLT3 gene expression cooperates to induce inferior prognosis in cytogenetically normal acute myeloid leukemia patients.

BACKGROUND: Acute myeloid leukemia (AML) is a bone marrow malignancy having multiple molecular pathways driving its progress. In recent years, the main causes of AML considered all over the world are genetic variations in cancerous cells. The RUNX1 and FLT3 genes are necessary for the normal hematopoiesis and differentiation process of hematopoietic stem cells into mature blood cells, therefore they are the most common targets for point mutations resulting in AML. METHODS: We screened 32 CN-AML patients for FLT3-ITD (by Allele-specific PCR) and RUNX1 mutations (by Sanger sequencing). The FLT3 mRNA expression was assessed in all AML patients and its subgroups. RESULTS: Eight patients (25%) carried RUNX1 mutation (K83E) while three patients (9.37%) were found to have internal tandem duplications in FLT3 gene. The RUNX1 mutation data were correlated with clinical parameters and FLT3 gene expression profile. The RUNX1 mutations were observed to be significantly prevalent in older males. Moreover, RUNX1 and FLT3-mutated patients had lower complete remission rate, event-free survival rate, and lower overall survival rate than patients with wild-type RUNX1 and FLT3 gene. The RUNX1 and FLT3 mutant patients with up-regulated FLT3 gene expression showed even worse prognosis. Bradford Assay showed that protein concentration was down-regulated in RUNX1 and FLT3 mutants in comparison to RUNX1 and FLT3 wild-type groups. CONCLUSION: This study constitutes the first report from Pakistan reporting significant molecular mutation analysis of RUNX1 and FLT3 genes including FLT3 expression evaluation with follow-up. This provides an insight that aforementioned mutations are markers of poor prognosis but the study with a large AML cohort will be useful to further investigate their role in disease biology of AML.

Salvadora persica protects libido by reducing corticosterone and elevating the testosterone levels in chronic cigarette smoke exposure rats.

BACKGROUND & OBJECTIVES: Cigarette smoke is associated with several diseased states including defects in reproductive behavior. Salvadora persica (S. persica) known as the toothbrush plant is reported to possess several pharmacological properties including antidepressants and anxiolytics. The present research was done to determine the libido-protective effect of S. persica in chronic cigarette smoke-exposed rats. MATERIALS AND METHODS: The decoction of freshly dried roots of S. persica (50, 100, and 200 mg/kg, oral) was administered to the chronic-cigarette smoke-exposed adult rats. The parameters related to libido were recorded using a close-camera circuit (CCTV). Serum corticosterone and testosterone levels were estimated. Further, the phytochemical constituents were identified in the decoction. The data obtained were analyzed using one-way analysis of variance and significance was considered at p < 0.05. RESULTS: The observation from the study revealed that cigarette smoke exposure reduces the sexual activity parameters significantly (p < 0.01), besides elevated the serum corticosterone and suppressed the testosterone levels in rats. Administration of S. persica at 200 mg/kg improved significantly (p < 0.05) the parameters related to libido. The decoction also reversed the changes in the levels of tested hormones in serum. INTERPRETATION AND CONCLUSION: The findings indicate that a 200 mg/kg S. persica decoction can protect libido in chronic cigarette smoke-exposed rats. The activity may be due to the presence of several phytoconstituents such as alkaloid, flavonoids and phytosterols that might produce vasodilatory effect in sex organs and enhance the synthesis of endogenous testosterone to improve libido characteristics weakened by chronic cigarette smoke exposure.