Synergistic effects of quercetin-loaded CoFe2O4@Liposomes regulate DNA damage and apoptosis in MCF-7 cancer cells: based on biophysical magnetic hyperthermia.

INTRODUCTION: Breast cancer (BC) is the most common malignancy in women globally. Significant progress has been made in developing structural nanoparticles (NPs) and formulations for targeted smart drug delivery (SDD) of pharmaceuticals, improving the precision of tumor cell targeting in therapy. SIGNIFICANCE: Magnetic hyperthermia (MHT) treatment using magneto-liposomes (MLs) has emerged as a promising adjuvant cancer therapy. METHODS: CoFe2O4 magnetic NPs (MNPs) were conjugated with nanoliposomes to form MLs, and the anticancer drug quercetin (Que) was loaded into MLs, forming Que-MLs composites for antitumor approach. The aim was to prepare Que-MLs for DD systems (DDS) under an alternating magnetic field (AMF), termed chemotherapy/hyperthermia (chemo-HT) techniques. The encapsulation efficiency (EE), drug loading capacity (DL), and drug release (DR) of Que and Que-MLs were evaluated. RESULTS: The results confirmed successful Que-loading on the surface of MLs, with an average diameter of 38 nm and efficient encapsulation into MLs (69%). In vitro, experimental results on MCF-7 breast cells using MHT showed high cytotoxic effects of novel Que-MLs on MCF-7 cells. Various analyses, including cytotoxicity, apoptosis, cell migration, western blotting, fluorescence imaging, and cell membrane internalization, were conducted. The Acridine Orange-ethidium bromide double fluorescence test identified 35% early and 55% late apoptosis resulting from Que-MLs under the chemo-HT group. TEM results indicated MCF-7 cell membrane internalization and digestion of Que-MLs, suggesting the presence of early endosome-like vesicles on the cytoplasmic periphery. CONCLUSIONS: Que-MLs exhibited multi-modal chemo-HT effects, displaying high toxicity against MCF-7 BC cells and showing promise as a potent cytotoxic agent for BC chemotherapy.

Effect of Chitosan/Gum Arabic Blends Enriched by Sodium Nitroprusside or Methyl Salicylate on the Storability and Antioxidant Activity of Tomato Fruit.

The impact of methyl salicylate (MeSA) or sodium nitroprusside (SNP) in chitosan (CS)/Gum Arabic (GA) mixture on physio-chemical characteristics and antioxidant status during the postharvest ripening of green tomato fruits was studied. CS/GA-MeSA at a 1 mM formulation was the best treatment to retard firmness and titratable acidity (TA) losses. Moreover, this formulation retarded pigmentation progress where it had the lowest significant values of total carotenes (TCs) and lycopene (LYP) contents until the 15th day of the storage period, as well as efficiently faced the rise in malondialdehyde (MDA) levels. Moreover, peroxidase (POD), polyphenol oxidase (PPO), catalase (CAT), and phenylalanine ammonia-lyase (PAL) activities of tomatoes treated with CS/GA-SNP at 2 mM were significantly better than that of control in the primary stages of storage. CS/GA-SNP at a 2 mM formulation showed an extremely high significant content of total polyphenol (TP) in the early stage of storage, while CS/GA and CS/GA-MeSA at 1 and 2 mM accumulated higher significant TP contents than uncoated fruits at the late stage of storage. All formulations were characterized by FTIR spectroscopy. Furthermore, the polymer formulations exhibited strong antifungal activity against Alternaria alternata and Botrytis cinerea as major pathogens of postharvest tomatoes. Transmission electron microscope (TEM) observations for the mycelia of both fungi treated by CS/GA-MeSA at 2 mM revealed serious ultrastructural damage, including distortion of the cell wall and cell membrane and degradation of cytoplasmic organelles.

Investigation of Roughness, Morphology, and Wettability Characteristics of Biopolymer Composite Coating on SS 316L for Biomedical Applications.

This project aims to create a 316L stainless steel coated with a biocomposite based on chitosan for use in the biomedical industry. To completely coat the material, the dip-coating technique was used to apply plain chitosan, chitosan nanosilver, chitosan biotin, and chitosan-nanosilver-biotin in that order. This coating's surface morphology was investigated with field emission scanning electron microscopy (FESEM). Surface roughness, average size distribution, and 2D and 3D surface tomography were all investigated using scanning probe microscopy and atomic force microscopy (SPM and AFM). The Fourier transform infrared (FTIR) spectroscopy technique was used to quantify changes in functional groups. To evaluate the coated samples' wettability, contact angle measurements were also performed. The chitosan (CS) + nanosilver, CS + biotin, and CS + biotin + nanosilver-coated 316L stainless steel showed roughness values of about 8.68, 4.21, and 3.3 nm, respectively, compared with the neat chitosan coating, which exhibits 12 nm roughness, indicating a strong effect of biotin and nanosilver on surface topography whereas the coating layers were homogenous, measuring around 33 nm in thickness. For CS + nanosilver and CS + biotin, the average size of agglomerates was approximately 444 nm and 355 nm, respectively. The coatings showed adequate wettability for biomedical applications, were homogeneous, and had no cracks. Their contact angles were around 51-75 degrees. All of these results point to the composite coating's intriguing potential for use in biological applications.

Smart Multivariate Spectrophotometric Determination of Two Co-Administered Autoimmune Drugs; Sulfasalazine and Pentoxifylline; in Bulk and Spiked Human Plasma.

BACKGROUND: Sulfasalazine and pentoxifylline are co-prescribed together to treat psoriasis and pemphigus vulgaris. Sulfasalazine is an anti-inflammatory, immunosuppressant, and antibiotic drug, while pentoxifylline is a vasodilator and immunosuppressant. The spectra of the two drugs and plasma suffer from severe overlap. OBJECTIVE: This work aims to simultaneously determine sulfasalazine and pentoxifylline in their binary mixture and spiked human plasma by the assessment of their UV spectral data. METHODS: Two model updated chemometric methods were established using principal component regression and partial least-squares regression models. The two models were validated in accordance with the U.S. Food and Drug Administration guidelines for bioanalysis and were applied for the determination of both drugs in synthetic mixtures or spiked human plasma. RESULTS: Accuracy and precision were within the accepted limits. In addition, three different assessment methods were used to evaluate the environmental greenness of the proposed models. CONCLUSION: The two updated models are simple, rapid, sensitive, and precise, and could be easily applied in QC laboratories for determination of sulfasalazine and pentoxifylline, without any preliminary separation steps or interference from plasma matrix. HIGHLIGHTS: Two updated chemometric models called principlal component regression and partial least-squares regression were established for determination of sulfasalazine and pentoxifylline in spiked human plasma using UV spectrophotometric data.

Evaluation of the Inhibitory Effect of Moringa oleifera Leaves Methanolic Extract against In Vitro Growth of Several Babesia Species and Theileria equi and the In Vivo Growth of Babesia microti.

The current study evaluated the inhibitory effect of Moringa oleifera leaves methanolic extract (MOL) against the in vitro growth of Babesia bovis (B. bovis), B. caballi, B. bigemina, and Theileria equi (T. equi), as well as in vivo growth of B. microti in mice. Active principles of MOL extract were determined using liquid chromatography mass spectrometry (LC-MS). MOL's anti-piroplasm efficacy was assessed both in vitro and in vivo using the SYBR Green I fluorescence assay. Every 96 hours, the hematological parameters, including red blood cell count (RBCs; 104/UL), hemoglobin content (HGB; g/dl), and hematocrit percent (HCT; %), in the treated mice were monitored using a Celltac MEK6450 automated hematological analyzer. LC-MS of MOL revealed that the most abundant polyphenolic catechism found in the MOL extract was isoquercetin and rutin. MOL inhibited B. bovis, B. caballi, B. bigemina, and T. equi in vitro growth in a dose-dependent way, with IC50 values of 45.29 ± 6.14, 19.16 ± 0.45, 137.49 ± 16.07, and 9.29 ± 0.014 µg/ml, respectively. MOL's in vitro antibabesial activity was enhanced when administrated simultaneously with either diminazene aceturate (DA) or MMV665875 compound from malaria box. In mice infected by B. microti, a combination of MOL and a low dose of DA (12.5 mg·kg-1) resulted in a significant (P < 0.05) reduction in B. microti growth. These findings suggest that MOL is an effective herbal anti-piroplasm therapy, especially when combined with a low dosage of either DA or MMV665875.

UGT1A1 morpholino antisense oligonucleotides produce mild unconjugated hyperbilirubinemia in cyclosporine A-induced cardiovascular disorders in BLC57 mice.

This study aimed to investigate the induction of mild unconjugated hyperbilirubinemia in hepatic UGT1A1 inhibition by Morpholinos antisense in CsA-treated BLC57 mice in comparison with the efficacy of chitosan (CH) as an anti-hypolipidemic natural product. Antisense morpholino oligonucleotides were injected intravenously into CsA-treated mice for 14 days thrice a week. Serum biochemical parameters, antioxidant status, and gene expression analysis of eNOS, PPAR-α, NF-kB, cFn, AT1-R, and ETA-R were determined in cardiac tissues with confirmation by histopathology. Inhibition of UGT1A1 significantly elevated serum unconjugated bilirubin within a physiological range. Furthermore, induced mild hyperbilirubinemia reduces hyperlipidemia, improves antioxidant status, and significantly increases the expression of the cardiac PPAR-α gene while decreasing, ETA-R, iNOS, NF-kB, cFn and AT1-R gene expression in CsA-treated mice. Importantly, mild unconjugated hyperbilirubinemia within physiological ranges may be used as a novel therapeutic strategy to lower hyperlipidemia, atherosclerosis, hypertension, and the CVD outcomes in CsA- treated transplant recipients.

Investigation of the potential roles of adipose stem cells and substances of natural origin in the healing process of E. coli infected wound model in Rats.

Skin infections by pathogenic microorganisms are a serious problem due to the potential of dissemination through the bloodstream to various organs causing toxic effects that may be up to mortality. Escherichia coli (E. coli) is one of the most predominant Gram-negative bacterial species present globally with great attention for investigation. The current study is designed to investigate the possible role of adipose tissue-derived stem cells (ADSCs), as well as natural products such as Trichoderma viride (T. viride) extract, Saccharomyces boulardii (S. boulardii) solution in the enhancement of wound healing process in the infected skin with E. coli. Ninety-six female rats were divided into 8 groups (12 animal/group): normal skin, wounded skin, wounded skin infected with E. coli, infected-wounded skin treated by ADSCs, infected-wounded skin treated by T. viride extract, infected-wounded skin treated by S. boulardii solution, infected-wounded skin treated a combination of treatments, infected-wounded skin treated by gentamicin. At day 21 animal weights and bacterial count were detected and compared. Animals were sacrificed and skin from various groups was investigated using a light microscope for sections stained by (hematoxylin eosin, Masson trichrome, and PCNA) as well as transmission electron microscopy. Pro-inflammatory (IL-1ß, TNF- α, and IL-13), anti-inflammatory cytokine (IL-4), and antioxidant enzymes (Superoxide dismutase, glutathione, and catalase) were assessed in various groups revealing that ADSCs lightly shift levels of these parameters in various rat groups to regular levels, while administration of T. viride extract, S. boulardii solution, their combination with ADSCs and gentamicin treatment drive the tested cytokines and enzymes to significant levels similar to a normal level where combination therapy gave the best result. The current findings revealed the possibility of using certain natural products as possible substitutes to regularly applied antibiotics with successive protective results in the wound infection model.

Human protozoa infection and dysplasia in ulcerative colitis: a neglected aspect in a prominent disease.

The chance of getting colorectal cancer (CRC) is higher in people with chronic ulcerative colitis (UC). The impact of parasitic infections on UC is underappreciated. The purpose of this study was to look into the effect of intestinal protozoal infections on the dysplastic changes generated by UC. The research included 152 adult patients with histologically confirmed UC and 152 healthy controls. Fecal samples were examined for the presence of parasites and fecal calprotectin (FC). The enzyme-linked immunosorbent assay measured serum anti-p53 antibodies (p53Abs) and metallothioneins (MTs). The advanced oxidation protein products (AOPPs) and reduced glutathione (GSH) levels were measured by a spectrophotometric method in all subjects. Serum C-reactive protein (CRP) and IL-6 were also measured. In addition, histopathological and immunohistochemical investigations of intestinal tissue were done. Our results exhibited significant increases in FC and CRP, IL-6, AOPPs, MTs, and p53Abs in ulcerative colitis patients with parasitic infections compared to those without parasites. In contrast, GSH levels showed a significant decrease in the same group compared with other groups. Histopathological and immunohistochemical assessments of intestinal tissue signified severe inflammation and strong expression of PD-L1 in patients with parasitic infections compared to others without parasitic infections. Our research indicated a greater frequency of intestinal protozoa in UC patients with elevated inflammatory and dysplastic biomarker levels. This suggests that these parasites may be involved in the etiology of chronic UC and the associated carcinogenetic process. This is the first report of a link between parasitic infections and dysplastic alterations in UC patients.

Surf Redfish-Based ZnO-NPs and Their Biological Activity with Reference to Their Non-Target Toxicity.

The marine environment is a rich source of bioactive compounds. Therefore, the sea cucumber was isolated from the Red Sea at the Al-Ain Al-Sokhna coast and it was identified as surf redfish (Actinopyga mauritiana). The aqueous extract of the surf redfish was utilized as an ecofriendly, novel and sustainable approach to fabricate zinc oxide nanoparticles (ZnO-NPs). The biosynthesized ZnO-NPs were physico-chemically characterized and evaluated for their possible antibacterial and insecticidal activities. Additionally, their safety in the non-target organism model (Nile tilapia fish) was also investigated. ZnO-NPs were spherical with an average size of 24.69 ± 11.61 nm and had a peak at 350 nm as shown by TEM and UV-Vis, respectively. XRD analysis indicated a crystalline phase of ZnO-NPs with an average size of 21.7 nm. The FTIR pattern showed biological residues from the surf redfish extract, highlighting their potential role in the biosynthesis process. DLS indicated a negative zeta potential (-19.2 mV) of the ZnO-NPs which is a good preliminary indicator for their stability. ZnO-NPs showed larvicidal activity against mosquito Culex pipiens (LC50 = 15.412 ppm and LC90 = 52.745 ppm) and a potent adulticidal effect to the housefly Musca domestica (LD50 = 21.132 ppm and LD90 = 84.930 ppm). Tested concentrations of ZnO-NPs showed strong activity against the 3rd larval instar. Topical assays revealed dose-dependent adulticidal activity against M. domestica after 24 h of treatment with ZnO-NPs. ZnO-NPs presented a wide antibacterial activity against two fish-pathogen bacteria, Pseudomonas aeruginosa and Aeromonas hydrophila. Histopathological and hematological investigations of the non-target organism, Nile tilapia fish exposed to 75-600 ppm ZnO-NPs provide dose-dependent impacts. Overall, data highlighted the potential applications of surf redfish-mediated ZnO-NPs as an effective and safe way to control mosquitoes, houseflies and fish pathogenic bacteria.

The Effect of Cerebrolysin in an Animal Model of Forebrain Ischemic-Reperfusion Injury: New Insights into the Activation of the Keap1/Nrf2/Antioxidant Signaling Pathway.

Forebrain ischemia-reperfusion (IR) injury causes neurological impairments due to decreased cerebral autoregulation, hypoperfusion, and edema in the hours to days following the restoration of spontaneous circulation. This study aimed to examine the protective and/or therapeutic effects of cerebrolysin (CBL) in managing forebrain IR injury and any probable underlying mechanisms. To study the contribution of reperfusion to forebrain injury, we developed a transient dual carotid artery ligation (tDCAL/IR) mouse model. Five equal groups of six BLC57 mice were created: Group 1: control group (no surgery was performed); Group 2: sham surgery (surgery was performed without IR); Group 3: tDCAL/IR (surgery with IR via permanently ligating the left CA and temporarily closing the right CA for 30 min, followed by reperfusion for 72 h); Group 4: CBL + tDCAL/IR (CBL was given intravenously at a 60 mg/kg BW dose 30 min before IR); and Group 5: tDCAL/IR + CBL (CBL was administered i.v. at 60 mg/kg BW three hours after IR). At 72 h following IR, the mice were euthanized. CBL administration 3 h after IR improved neurological functional recovery, enhanced anti-inflammatory and antioxidant activities, alleviated apoptotic neuronal death, and inhibited reactive microglial and astrocyte activation, resulting in neuroprotection after IR injury in the tDCAL/IR + CBL mice group as compared to the other groups. Furthermore, CBL reduced the TLRs/NF-kB/cytokines while activating the Keap1/Nrf2/antioxidant signaling pathway. These results indicate that CBL may improve neurologic function in mice following IR.

Development of HPLC-UV Method for Simultaneous Determination of Corticosteroid Co-Administered Immune Therapy.

Prednisolone (PDS) has recently been utilized to treat a variety of medical disorders, including autoimmune illnesses and cancer. It is also used to treat coronavirus disease 2019 infection-related respiratory problems. Because it may induce health problems including gastrointestinal lesions and ulceration, it has to be used alongside other drugs like esomeprazole (ESM), which acts as a proton pump antagonist to reduce the probability of ulceration. As a result, the goal of this research is to create an environmentally safe and sensitive high-performance liquid chromatography (HPLC) approach for determining PDS and ESM in their binary combination and spiked human plasma. C8 column (100 × 4.6 mm, 5 µm) and gradient mobile phase elution were used to separate the studied drugs with ultraviolet recognition at 290 nm. Caffeine was utilized as an internal standard to adjust the sample variance. Plasma, caffeine, ESM and PDS all had tR values of 1.4, 3.5, 6.3 and 7.3, respectively. The suggested method's greenness features were evaluated using three greenness evaluation tools: green analytical procedure index, analytical greenness metric approach and analytical eco-scale, and the findings were approved and satisfied. Validation parameters were evaluated in accordance with US-FDA recommendations in order to meet the global desires for biological analysis technique, acceptable limits were obtained.

Predictors of Consanguinity Marriage Decision in Saudi Arabia: A Pilot Study.

Consanguineous marriages are common in Saudi Arabia, increasing the risk of genetic blood disorders in offspring. This pilot study assessed the knowledge and perceived threats regarding genetic blood disorders, norms, and premarital screening for consanguineous marriage among unmarried university students in Saudi Arabia as a predictor of marriage decisions. A cross-sectional study was conducted from 22 January through 22 April 2022. In total, 400 unmarried students at Saudi Arabian universities were recruited using the non-probability convenience sampling technique. The data were analyzed using descriptive statistics and multinomial logistic regression. The results showed that the majority of participants had poor knowledge of genetic blood disorders. Most of the participants had a favorable attitude toward consanguineous marriage, while perceived threats towards genetic blood disorders were perceived as neutral by the participants. Moreover, their norms regarding consanguineous marriage also showed neutral results. A multinomial regression shows that participants with poor attitudes were significantly 22.3 times more likely to have poor marriage decisions (95% CI: 4.9-101.7, p < 0.001). However, participants with good and neutral norms regarding consanguinity marriage were significantly protective factors against poor marriage decisions with an RRR ratio of 0.165 (95% CI:0.030-0.918, p = 0.04) and 0.238 (95% CI: 0.071-0.797, p = 0.02), respectively. To mitigate the risk of genetic blood disorders in future generations, there is a need for targeted awareness campaigns about genetic blood disorders and the risks of consanguineous marriages by integrating this education into university curricula, and premarital counseling. It is also important to address societal norms, promoting informed decision-making, and provide premarital consultation to couples who carry the same mutated genes and are at risk of transmitting the disease to their offspring. Furthermore, there is a need for further research to assess the effectiveness of campaigns in this regard.

GC-MS Analysis, Antibacterial, and Anticancer Activities of Hibiscus sabdariffa L. Methanolic Extract: In Vitro and In Silico Studies.

The emergence of bacteria that are resistant to several antibiotics has represented a serious hazard to human health globally. Bioactive metabolites from medicinal plants have a wide spectrum of therapeutic possibilities against resistant bacteria. Therefore, this study was performed to investigate the antibacterial efficacy of various extracts of three medicinal plants as Salvia officinalis L., Ziziphus spina-christi L., and Hibiscus sabdariffa L. against pathogenic Gram-negative Enterobacter cloacae (ATCC13047), Pseudomonas aeruginosa (RCMB008001), Escherichia coli (RCMB004001), and Gram-positive Staphylococcus aureus (ATCC 25923), bacteria using the agar-well diffusion method. Results revealed that, out of the three examined plant extracts, the methanol extract of H. sabdariffa L. was the most effective against all tested bacteria. The highest growth inhibition (39.6 ± 0.20 mm) was recorded against E. coli. Additionally, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the methanol extract of H. sabdariffa were detected in the case of all tested bacteria. Moreover, an antibiotic susceptibility test revealed that all tested bacteria showed multidrug resistance (MDR). While 50% of tested bacteria were sensitive and 50% were intermediately sensitive to piperacillin/tazobactam (TZP) based on the inhibition zone but still less than the extract. Synergistic assay demonstrated the promising role of using a combination of H. sabdariffa L. and (TZP) against tested bacteria. A surface investigation using a scanning electron microscope of the E. coli treated with TZP, extract, or a combination of the two revealed extremely considerable bacterial cell death. In addition, H. sabdariffa L. has a promising anticancer role versus Caco-2 cells with IC50 of 17.51 ± 0.07 µg/mL and minimal cytotoxicity upon testing versus Vero cells with CC50 of 165.24 ± 0.89 µg/mL. Flow cytometric analysis confirmed that H. sabdariffa extract significantly increased the apoptotic rate of Caco-2-treated cells compared to the untreated group. Furthermore, GC-MS analysis confirmed the existence of various bioactive components in the methanol hibiscus extract. Utilizing molecular docking with the MOE-Dock tool, binding interactions between n-Hexadecanoic acid, hexadecanoic acid-methyl ester, and oleic acid, 3-hydroxypropyl ester were evaluated against the target crystal structures of E. coli (MenB) (PDB ID:3T88) and the structure of cyclophilin of a colon cancer cell line (PDB ID: 2HQ6). The observed results provide insight into how molecular modeling methods might inhibit the tested substances, which may have applications in the treatment of E. coli and colon cancer. Thus, H. sabdariffa methanol extract is a promising candidate to be further investigated for developing alternative natural therapies for infection treatment.

Beyond mechanical loading: The metabolic contribution of obesity in osteoarthritis unveils novel therapeutic targets.

Osteoarthritis (OA) is a prevalent progressive disease that frequently coexists with obesity. For several decades, OA was thought to be the result of ageing and mechanical stress on cartilage. Researchers' perspective has been greatly transformed when cumulative findings emphasized the role of adipose tissue in the diseases. Nowadays, the metabolic effect of obesity on cartilage tissue has become an integral part of obesity research; hoping to discover a disease-modifying drug for OA. Recently, several adipokines have been reported to be associated with OA. Particularly, metrnl (meteorin-like) and retinol-binding protein 4 (RBP4) have been recognized as emerging adipokines that can mediate OA pathogenesis. Accordingly, in this review, we will summarize the latest findings concerned with the metabolic contribution of obesity in OA pathogenesis, with particular emphasis on dyslipidemia, insulin resistance and adipokines. Additionally, we will discuss the most recent adipokines that have been reported to play a role in this context. Careful consideration of these molecular mechanisms interrelated with obesity and OA will undoubtedly unveil new avenues for OA treatment.

Comparative effects of finasteride and laser-irradiated silver nanoparticles on testicular function and histology in testosterone induced benign prostatic hyperplasia in rats.

AIMS: The objective of this study was to compare the effects of finasteride, a medication used to treat benign prostatic hyperplasia (BPH), and laser irradiated silver nanoparticles (AgNPs), a potential candidate for BPH therapy (Sanchez-Salas, 2017; Marghani et al., 2022) [1,2], on the sex hormone profiles, sperm quality, steroidogenesis, testicular oxidative stress, and histomorphology changes in BPH rats. MATERIALS AND METHODS: BPH was induced in male Sprague-Dawley (SD) rats via intramuscular (i.m.) injection of 5 mg/kg BW testosterone propionate (TP) for 14 days. Once the BPH model was induced, rats were divided into four groups (n = 6) as follows: the control group; the BPH group; the BPH/Fina group, which received 5 mg/kg BW finasteride by oral gavage daily for 14 days; and the BPH/AgNPs group, which received a daily intraperitoneal (i.p.) injection of 50 mg/kg BW AgNPs, followed by 5min of exposure to a 532 nm NIR laser in the prostatic area for the constitutive 14 days. KEY FINDINGS: On day 14, the BPH rats had a significant increase in prostate specific antigen (PSA), dihydrotestosterone, and prostate weights, while testicular weights and sperm quality were significantly lower than in the control rats. On day 28, laser irradiated AgNps treated BPH rats showed improved sex hormone balance, testicular weights, sperm quality, steroidogenesis, and an ameliorative effect on testicular histopathology compared to finasteride. SIGNIFICANCE: Surprisingly, these findings suggest that laser irradiated AgNPs can be used as an alternative therapy to finasteride for the treatment of BPH without causing negative effects on the testes.

Anticandidal activity of nanocomposite based on nanochitosan, nanostarch and mycosynthesized copper oxide nanoparticles against multidrug-resistant Candida.

Recently, antimicrobial resistance has increased globally particularly Candida infections. Most of antifungal drugs used for treating candidiasis became resistant to most of Candida species. In the current study, a nanocomposite based on mycosynthesized copper oxide nanoparticles (CuONPs), nanostarch, nanochitosan was prepared. Results illustrated that twenty-four Candida isolates were isolated from clinical samples. Furthermore, three Candida strains were selected as the most resistant among others toward commercial antifungal drugs; these selected strains were identified genetically as C. glabrata MTMA 19, C. glabrata MTMA 21 and C. tropicalis MTMA 24. Characterization of the prepared nanocomposite was carried out using physiochemical analysis included Ultraviolet-visible spectroscopy (Uv-Vis), Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Energy-Dispersive X-ray spectroscopy (EDX) and Transmission Electron Microscopy (TEM). Moreover, the nanocomposite exhibited promising anticandidal activity against C. glabrata MTMA 19, C. glabrata MTMA 21 and C. tropicalis MTMA 24, where the inhibition zones were 15.3, 27 and 28 mm, respectively. Ultrastructure changes observed in nanocomposite-treated C. tropicalis demonstrated disruption of the cell wall which led to cell death. In conclusion, our results confirmed that the novel biosynthesized nanocomposite based on mycosynthesized CuONPs, nanostarch and nanochitosan is a promising anticandidal agent to fight multidrug-resistant Candida.

The combined effect of zinc oxide nanoparticles and milrinone on acute renal ischemia/reperfusion injury in rats: Potential underlying mechanisms.

AIM: To investigate the efficacy of zinc oxide nanoparticles (ZnO-NPs) and/or milrinone (MIL) on renal ischemia/reperfusion injury (I/RI) in rats and their possible underlying mechanisms. MATERIALS AND METHODS: Forty-eight adult male Sprague-Dawley albino rats were randomly assigned into six equal-sized groups (n = 8): normal control, sham-operated, I/R group (45 min/24 h), ZnO-NPs group (10 mg/kg i.p.), MIL group (0.5 mg/kg i.p.), and ZnO-NPs + MIL group in the same previous doses. KEY FINDINGS: In comparison to the I/R-operated group, administration of either ZnO-NPs or MIL significantly decreased serum creatinine and urea concentrations, and renal vascular permeability (p < 0.05). The oxidative stress was significantly declined, as evidenced by increased GPx, CAT, and SOD activities and decreased MDA and NO concentrations. Renal expressions of TNF-α, NF-κB, KIM-1, NGAL, and caspase-3 decreased significantly, while Nrf2 increased significantly. Histopathology investigation revealed improvement with minimal renal lesions and fibrosis after ZnO-NPs or MIL treatments. The combined treatments synergistically improved the studied parameters more than either treatment alone. These findings were validated by molecular modeling, which revealed that MIL inhibited TNF-α, NF-kB, caspase-3, KIM-1 and NGAL. SIGNIFICANCE: Both ZnO-NPs and MIL exerted cytoprotective effects against acute renal I/RI, and a combination of both was found to be even more effective. This renoprotective effect is suggested to be mediated through activation of Nrf2 and the prevention of the NF-κB activation-induced oxidative stress and inflammation, which may strengthen the potential role of ZnO-NPs or MIL in renal I/RI protection during surgical procedures.

A validated ecofriendly chromatographic method for determination of myasthenia gravis combined medications in spiked human plasma.

Recently, the main interest of analytical chemistry researchers has been the development of green analytical methods to minimize harmful effects on the environment and natural life. Therefore, an RP-HPLC method was developed and assessed regarding its greenness criteria using three greenness assessment tools: an analytical eco-scale, an analytical greenness metric approach and a green analytical procedure index. This method aims to separate and quantitatively determine three co-administered drugs, namely pyridostigmine bromide (PYR), 6-mercaptopurine (MRC) and prednisolone (PRD), in their tertiary mixture and spiked human plasma. These drugs are co-administered to manage myasthenia gravis autoimmune disease. The separation was done using a C18 column and a gradient elution of a mixture of 0.1% H3 PO4 aqueous solution (pH 2.3) and methanol. The flow rate was adjusted to 1 ml/min and detection was done at 254 (for PYR and PRD) and at 330 nm (for MRC). The lower limits of quantitation were 15, 2, and 5 µg/ml for PYR, MER and PRD, respectively. Linear correlations were obtained and found to be near 1. In addition, the proposed method was validated according to the US Food and Drug Administration's instructions, and the results proved its success to determine the three studied drugs in their tertiary mixture and spiked human plasma.

DNA polymorphisms and expression profile of immune and antioxidant genes as biomarkers for reproductive disorders tolerance/susceptibility in Baladi goat.

The objective of this study was to explore single nucleotide polymorphisms (SNPs) and gene expression of immune and antioxidant markers associated with reproductive disorders in Baladi goats. A total of one hundred adults Baladi does were allocated into two equal-sized groups: normal reproductive performance and does have a history of reproductive disorders. DNA sequencing of PRLR (304-bp), LTF (904-bp), TLR2 (420-bp), TLR4 (335-bp), CLA-DRB3.2 (285-bp), SOD3 (735-bp), CAT (1526-bp), GPX4 (782-bp), and GST (690-bp) revealed SNPs associated with reproductive disorders tolerance/susceptibility in investigated does. Nonetheless, DNA sequencing of beta defensin (483-bp), CCL5 (840-bp), and ATOX1 (374-bp) genes elicited a monomorphic pattern. Levels of PRLR, LTF, TLR2, TLR4, CLA-DRB3.2, beta defensin, and CCL5 genes were significantly up-regulated in does affect with reproductive disorders than tolerant ones; while SOD3, CAT, GPX4, GST and ATOX1 genes pattern elicited an opposite trend. The results herein confirmed the potential significance of SNPs in immune and antioxidant genes as genetic markers for reproductive disorders tolerance/susceptibility in Baladi does. The Gene expression profile of investigated genes could be also used as proxy biomarkers for the prediction of the most susceptible risk time for disease occurrence and for building up an effective management protocol.

Potential Antimicrobial and Antibiofilm Properties of Copper Oxide Nanoparticles: Time-Kill Kinetic Essay and Ultrastructure of Pathogenic Bacterial Cells.

Mycosynthesis of nanoparticle (NP) production is a potential ecofriendly technology for large scale production. In the present study, copper oxide nanoparticles (CuONPs) have been synthesized from the live cell filtrate of the fungus Penicillium chrysogenum. The created CuONPs were characterized via several techniques, namely Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX). Furthermore, the biosynthesized CuONPs were performed against biofilm forming Klebsiella oxytoca ATCC 51,983, Escherichia coli ATCC 35,218, Staphylococcus aureus ATCC 25,923, and Bacillus cereus ATCC 11,778. The anti-bacterial activity result was shown with the zone of inhibition determined to be 14 ± 0.31 mm, 16 ± 0.53 mm, 11 ± 0.57 mm, and 10 ± 0.57 mm respectively. Klebsiella oxytoca and Escherichia coli were more susceptible to CuONPs with minimal inhibitory concentration (MIC) values 6.25 and 3.12 µg/mL, respectively, while for Staphylococcus aureus and Bacillus cereus, MIC value was 12.5 and 25 µg/mL, respectively. The minimum biofilm inhibition concentration (MBIC) result was more evident, that the CuONPs have excellent anti-biofilm activity at sub-MIC levels reducing biofilm formation by 49% and 59% against Klebsiella oxytoca and Escherichia coli, while the results indicated that the MBIC of CuONPs on Bacillus cereus and Staphylococcus aureus was higher than 200 µg/mL and 256 µg/mL, respectively, suggesting that these CuONPs could not inhibit mature formatted biofilm of Bacillus cereus and Staphylococcus aureus in vitro. Overall, all the results were clearly confirmed that the CuONPs have excellent anti-biofilm ability against Klebsiella oxytoca and Escherichia coli. The prepared CuONPs offer a smart approach for biomedical therapy of resistant microorganisms because of its promoted antimicrobial action, but only for specified purposes.