Nicotine exacerbates liver damage in a mice model of Ehrlich ascites carcinoma through shifting SOD/NF-κB/caspase-3 pathways: ameliorating role of Chlorella vulgaris.

Nicotine, a pervasive global environmental pollutant, is released throughout every phase of the tobacco's life cycle. This study examined the probable ameliorative role of Chlorella vulgaris (ChV) extract against nicotine (NIC)-induced hepatic injury in Ehrlich ascites carcinoma (EAC) bearing female Swiss mice. Sixty female Swiss mice were assigned to four equal groups orally gavaged 2% saccharin 0.2 mL/mouse (control group), orally intubated 100 mg ChV /kg (ChV group), orally intubated 100 µg/mL NIC in 2% saccharin (NIC group), and orally intubated NIC + ChV as in group 3 and 2 (NIC+ChV group). The dosing was daily for 4 weeks. Mice from all experimental groups were then inoculated intraperitoneally with viable tumor cells 2.5 × 106 (0.2 mL/mouse) in the fourth week, and the treatments were extended for another 2 weeks. The results have shown that NIC exposure significantly altered the serum levels of liver function indices, lipid profile, LDH, and ALP in the NIC-exposed group. NIC administration significantly increased hepatic inflammation, lipid peroxidation, and DNA damage-related biomarkers but reduced antioxidant enzyme activities. NIC exposure downregulated SOD1, SOD2, CAT, GPX1, and GPX2 but upregulated NF-κB hepatic gene expression. Notably, the presence of the EAC cells outside the liver was common in all mice groups. Liver tissue of the NIC-exposed group showed multifocal expansion of hepatic sinusoids by neoplastic cells. However, with no evidence of considerable infiltration of EAC cells inside the sinusoids or in periportal areas in the NIC + ChV groups. NIC significantly altered caspase-3, Bax, and BcL2 hepatic immune expression. Interestingly, ChV administration significantly mitigates NIC-induced alterations in hepatic function indices, lipid profile, and the mRNA expression of antioxidant and NF-κB genes and regulates the caspase-3, Bax, and BcL2 immunostaining. Finally, the in vivo protective outcomes of ChV against NIC-induced hepatic injury combined with EAC in female Swiss mice could suggest their helpful role for cancer patients who are directly or indirectly exposed to NIC daily.

Evaluation of Antiemetic Consistency in Chemotherapy-Induced Nausea and Vomiting Among NHL Patients in Sana'a, Yemen.

Background: Chemotherapy-induced nausea and vomiting (CINV) is a prevalent and distressing adverse effect that can negatively affect a patient's quality of life and treatment adherence. Purpose: This study aimed to evaluate the consistency of antiemetic use with standard guidelines and to examine the factors influencing it. Methods: This cross-sectional study was conducted at the National Oncology Center (NOC) of Al-Jomhouri Teaching Hospital, Sana'a, Yemen, from November 2022 to September 2023. Demographic data, chemotherapy and antiemetic regimens, dosages, and patient-related risk factors were collected via direct interviews, medical records, and treatment charts. This study evaluated the consistency of antiemetic practices among non-Hodgkin's Lymphoma (NHL) patients using the National Comprehensive Cancer Network (NCCN) guidelines. The chi-squared test and regression were used to determine the factors associated with guideline consistency. Results: A total of 251 patients with NHL were recruited for the study; 57.4% were male and 60.6% were aged between 18-49. Most of the patients received moderately emetogenic chemotherapy (81.3%). The overall consistency with the NCCN guidelines was only 23.9%, with antiemetic drug selection and dosage reported inconsistently in 62.9% and 16.7% of patients, respectively. Furthermore, 62.5% of the patients received an under-prescribed antiemetic prophylactic regimen. Treatment duration, number of chemotherapy cycles, emetogenic risk potential, and overall patient risk, as well as age, sex, and marital status, were significantly associated with guideline inconsistency (p < 0.05). Conclusion: This study revealed a notable gap in the consistency of antiemetic prescriptions among patients with NHL. Inappropriate drug selection, dosing, and under-prescription are common problems. Patient regimen risk factors significantly influenced the consistency of the National Comprehensive Cancer Network guidelines. Personalized approaches are essential to enhance adherence to guidelines and improve antiemetic strategies.

Effects of 5-fluorouracil, thymoquinone, and mammary stem cells' exosomes on in vitro cultured breast cancer cells.

Background: 5-fluorouracil (5-FU) is an antimetabolic agent used for treating slowly growing solid tumors like breast and ovarian carcinoma. Thymoquinone (TQ) is the main biologically active constituent of Nigella sativa, it has been found to demonstrate anticancerous effects in several preclinical studies, and this is because TQ possesses multitarget nature. Stem cells-derived exosomes are in the spotlight of research and are promising tissue regenerative and anticancer cell-derived nanovesicles. Aim: Herein, we studied the antineoplastic effects of Exosomes derived from mammary stem cells (MaSCs-Exo) on breast cancer cells, alone or combined with TQ when compared to a breast cancer chemotherapeutic agent; 5-FU. Methods: Our approach included performing viability test and measuring the expression of pro-apoptotic gene (Bax), anti-apoptotic gene (BCL-2) and angiogenic gene (VEGF) on Human MCF-7 cells (breast adenocarcinoma cells), the MCF-7 cells were cultured and incubated with medium containing 5-FU (25 µg/ml), TQ (200 µg/ml), MaSCs-Exo (100 µg protein equivalent), a combination of TQ (200 µg/ml) and MaSCs-Exo (100 µg). Results: Our obtained results show that TQ and MaSCs-Exo each can effectively inhibit breast cancer cell line (MCF-7) proliferation and growth. Also, the results show that the combination of TQ and MaSCs-Exo had higher cytotoxic effects on MCF-7 breast cancer cells than TQ or 5-FU, alone. Conclusion: The present study shows a promising anticancer potential of exosomes isolated from mammary stem cells; this effect was potentiated by adding TQ with MaSCs-derived exosomes.

Effect of vinpocetine against acrylamide-induced nephrotoxicity in rats.

Vinpocetine (VIN) is a synthetic drug derived from the natural alkaloid vincamine. The antioxidation and anti-inflammation effects of VIN allow it to be used for multiple therapeutic purposes. So, the research aims to discover the possibility of using VIN to improve the nephrotoxicity of acrylamide (ACR). Twenty-four male albino rats were used in the trial: rats in the control group received 0.5 mL of oral saline, rats in the VIN group received an oral dose of VIN (5 mg/kg), rats in the ACR group received an oral dose of ACR (38.27 mg/kg), and rats in the VIN + ACR group received VIN and then ACR 1 h later. Rat blood and kidneys were collected 10 days after the experiment began to assess biochemical parameters and to examine both renal histopathological and immunohistochemistry. The ACR-treated rats showed high levels of serum kidney function biomarkers (creatinine, urea, and uric acid), serum protein biomarkers (total protein, albumin, and globulin), renal kidney injury molecule (KIM)-1, renal malondialdehyde (MDA), and renal caspase-3 immunoexpression. Moreover, ACR lowed both renal superoxide dismutase (SOD) activity and renal glutathione (GSH) level and caused renal histological alterations. While administration of VIN improved serum kidney function biomarkers, serum protein biomarkers, renal KIM-1, renal oxidative stress biomarkers (MDA, SOD, and GSH), renal caspase-3 immunoexpression, and renal histological alterations induced by ACR. The study confirmed the ability of VIN to reduce the nephrotoxic effects of ACR, which was evident through the results of biochemical parameters and histological and immunohistochemical examinations of the kidney tissues.

Chlorella vulgaris extract conjugated magnetic iron nanoparticles in nile tilapia (Oreochromis niloticus): Growth promoting, immunostimulant and antioxidant role and combating against the synergistic infection with Ichthyophthirius multifiliis and Aeromonashydrophila.

Nile tilapia reared under intensive conditions was more susceptible for Ichthyophthirius multifilii (I. multifiliis) infection eliciting higher mortality, lower productive rate and further bacterial coinfection with Aeromonas hydrophila (A. hydrophila). The higher potency of magnetic field of iron oxide nanoparticles (NPs) can kill pathogens through inhibiting their viability. Herein, coating of Chlorella vulgaris extract (ChVE) with magnetic iron oxide NPs (Mag iron NPs) can create an external magnetic field that facilitates their release inside the targeted tissues. Thus, the current study is focused on application of new functionalized properties of Mag iron NPs in combination with ChVE and their efficacy to alleviate I. multifiliis and subsequent infection with A. hydrophila in Nile tilapia. Four hundred fingerlings were divided into: control group (with no additives), three groups fed control diet supplemented with ChVE, Mag iron NPs and ChVE@Mag iron NPs for 90 days. At the end of feeding trial fish were challenged with I. multifiliis and at 9 days post challenge was coinfected by A. hydrophila. A remarkable higher growth rate and an improved feed conversion ratio were detected in group fed ChVE@Mag iron-NPs. The maximum expression of antioxidant enzymes in skin and gills tissues (GSH-Px, CAT, and SOD) which came in parallel with higher serum activities of these enzymes was identified in groups received ChVE@Mag iron-NPs. Furthermore, group fed a combination of ChVE and Mag iron-NPs showed a boosted immune response (higher lysozyme, IgM, ACH50, and MPO) prior to challenge with I. multifiliis. In contrast, fish fed ChVE@Mag iron-NPs supplemented diet had lower infection (decreased by 62%) and mortality rates (decreased by 84%), as well as less visible white spots (decreased by 92 % at 12 dpi) on the body surfaces and mucous score. Interestingly, post I. multifiliis the excessive inflammatory response in gill and skin tissues was subsided by feeding on ChVE@Mag iron-NPs as proved by down regulation of IL-1ß, TNFα, COX-2 and iNOS and upregulation of IL-10, and IgM, IgT and Muc-2 genes. Notably, group exposed to I. multifiliis-showed higher mortality when exposed to Aeromonas hydrophilia (increased by 43 %) while group fed ChVE@Mag iron-NPs exhibited lower morality (2%). Moreover, the bacterial loads of A. hydrophilia in fish infected by I. multifiliis and fed control diet were higher than those received dietary supplement of ChVE, Mag iron-NPs and the most reduced load was obtained in group fed ChVE@Mag iron-NPs at 7 dpi. In conclusion, ChVE@Mag iron-NPs fed fish had stronger immune barrier and antioxidant functions of skin and gills, and better survival following I. multifiliis and A. hydrophilia infection.

Prospects of new targeted nanotherapy combining liponiosomes with berberine to combat colorectal cancer development: An in vivo experimental model.

Colorectal cancer (CRC) is one of the most identified and deadly malignancies worldwide. It presents a serious challenge due to its quick growth, which finally culminates in severe malignancy. It is critical to improve the efficacy of berberine (BR) as an anticancer agent to overcome its limited bioavailability. Implementation of a novel, effective nanocarrier system of liponiosomes for BR (LipoNio.BR) can support mechanistic actions associated with its anti-CRC role. Following CRC induction in rats using 1,2 Dimethylhydrazine (40 mg DMH/kg/week), the potency and mechanistic actions of LipoNio.BR were assessed by evaluating the lesion severity and molecular mechanisms controlling oxidative stress, apoptosis, autophagy, and inflammatory responses, and conducting histopathological and immunohistochemistry examinations of colonic tissues. The results indicated that the severity of clinical signs comprising weight gain loss, increased diarrhea and rectal bleeding, and reduced survivability were greatly restored in the LipoNio.BR-treated group. LipoNio.BR remarkably reduced CRC development compared to FBR (free berberine), as it induced apoptosis via upregulating apoptotic genes (Bax and caspase3, increased up to 7.89 and 6.25-fold, respectively) and downregulating the anti-apoptotic gene Bcl-2 by 2.25-fold. LipoNio.BR mitigated the oxidative stress associated with CRC and maintained redox homeostasis. Notably, the excessive inflammatory response associated with CRC was prominently reduced following administration of LipoNio.BR [which decreased iterleukin (IL-B, IL-6), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), proliferating cell nuclear antigen (PCNA), follistatin, and activin BA (beta-A) expression]. LipoNio.BR modulated the expression of nuclear factor kappa B (NF-κB) and mammalian target of rapamycin (mTOR), which impacted tumor vascularity (decreased Vascular endothelial growth factor (VEGF) expression by 2.36-fold). The severity of the histopathological alterations in the colonic tissues, including the development of neoplastic epithelium and the invasion of some neoplastic masses, was greatly reduced in the LipoNio.BR group compared to the FBR-(free berberine) administrated group. Following CRC induction, immunohistochemical staining revealed that the overexpression of cyclin and COX-2 in colonic tissues were suppressed in the LipoNio.BR group. Taken together, these findings suggest that LipoNio.BR has a potential role in reducing CRC progression to a greater extent compared to free BR and could be considered a promising and potent therapy against CRC.

Novel Antioxidant Insights of Myricetin on the Performance of Broiler Chickens and Alleviating Experimental Infection with Eimeria spp.: Crosstalk between Oxidative Stress and Inflammation.

In the modern poultry industry, the application of novel phytogenic bioactive compounds with antioxidant potential aims to enhance productivity and quality and to minimize the stress of associated diseases. Herein, myricetin, a natural flavonoid, was evaluated for the first time on broiler chickens' performance, antioxidants and immune modulating functions, and tackling avian coccidiosis. A total of 500 one-day-old chicks were divided into five groups. The negative (NC) and infected control (IC) groups were fed a control diet without additives, and the latter was infected with Eimeria spp. Groups supplemented with myricetin (Myc) were fed a control diet of Myc (200, 400 and 600 mg/kg diet each). On d 14, all chicks except those in NC were challenged with oocysts of mixed Eimeria spp. Significant improvements in the overall growth rate and feed conversion ratio were detected in the group that was fed 600 mg/kg, unlike the IC group. Notably, groups that were fed 400 and 600 mg/kg showed higher total meat antioxidant capacity with an inverse reduction in oxidative and lipid peroxidation biomarkers (hydrogen peroxide: H2O2; reactive oxygen species: ROS; Malondialdehyde: MDA). Of note, the upregulation of glutathione peroxidase; GSH-Px, catalase; CAT, superoxide dismutase; SOD, heme oxygenase-1; HO-1 and NAD(P)H dehydrogenase quinone 1 NQO1 genes in jejunum and muscle were prominently observed with increasing levels of supplemental Myc. At 21 dpi, the severity of coccoidal lesions (p < 0.05) induced by mixed Eimeria spp. and oocyst excretion were greatly reduced in the group that was fed 600 mg/kg of Myc. In the IC group, higher serum levels of C-reactive protein; CRP and nitric oxide; and NO and the upregulated expression of inflammatory biomarkers (interleukin-1ß; IL-1ß, interleukin-6; IL-6, tumor necrosis factor-α; TNF-α, chemotactic cytokines; CCL20, stromal cell-derived factor-1; CXCL13, and avian defensins; AvBD612) were subsided in higher levels in the Myc-fed groups. Taken together, these findings indicate the promising antioxidant role of Myc in modulating immune responses and reducing growth depression associated with coccidia challenges.

Impact of resveratrol-loaded liposomal nanocarriers on heat-stressed broiler chickens: Effects on performance, sirtuin expression, oxidative stress regulators, and muscle building factors.

Climate change is considered to be the primary cause of heat stress (HS) in broiler chickens. Owing to the unique properties of extracted polyphenols, resveratrol-loaded liposomal nanoparticles (Resv-Lipo NPs) were first explored to mitigate the harmful effects of HS. The dietary role of Resv-Lipo NPs in heat-stressed birds was investigated based on their growth performance, antioxidative potential, and the expression of heat shock proteins, sirtuins, antioxidant, immune, and muscle-building related genes. A total of 250 1-day-old Ross 308 broiler chickens were divided into five experimental groups (5 replicates/group, 10 birds/replicate) for 42 days as follows: the control group was fed a basal diet and reared in thermoneutral conditions, and the other four HS groups were fed a basal diet supplemented with Resv-Lipo NPsI, II, and III at the levels of 0, 50, 100, and 150 mg/kg diet, respectively. The results indicated that supplementation with Resv-Lipo NP improved the growth rate of the HS group. The Resv-Lipo NP group showed the most significant improvement in body weight gain (p < 0.05) and FCR. Additionally, post-HS exposure, the groups that received Resv-Lipo NPs showed restored functions of the kidney and the liver as well as improvements in the lipid profile. The restoration occurred especially at higher levels in the Resv-Lipo NP group compared to the HS group. The elevated corticosterone and T3 and T4 hormone levels in the HS group returned to the normal range in the Resv-Lipo NPsIII group. Additionally, the HS groups supplemented with Resv-Lipo NPs showed an improvement in serum and muscle antioxidant biomarkers. The upregulation of the muscle and intestinal antioxidant-related genes (SOD, CAT, GSH-PX, NR-f2, and HO-1) and the muscle-building genes (myostatin, MyoD, and mTOR) was observed with increasing the level of Resv-Lipo NPs. Heat stress upregulated heat shock proteins (HSP) 70 and 90 gene expression, which was restored to normal levels in HS+Resv-Lipo NPsIII. Moreover, the expression of sirtuin 1, 3, and 7 (SIRT1, SIRT3, and SIRT7) genes was increased (p < 0.05) in the liver of the HS groups that received Resv-Lipo NPs in a dose-dependent manner. Notably, the upregulation of proinflammatory cytokines in the HS group was restored in the HS groups that received Resv-Lipo NPs. Supplementation with Resv-Lipo NPs can mitigate the harmful impact of HS and consequently improve the performance of broiler chickens.

Liposomal encapsulated oregano, cinnamon, and clove oils enhanced the performance, bacterial metabolites antioxidant potential, and intestinal microbiota of broiler chickens.

Encapsulated phytochemicals with augmented therapeutic and nutritional characteristics have become promising alternatives to antimicrobials in the poultry industry. Hence, our key target was to explore the efficacy of liposomal encapsulation, as a novel carrier, for essential oils (LEOs) on growth, digestibility, intestinal microbiota, and bacterial metabolites of broiler chickens. Moreover, the impact of encapsulated EOs on transcription mechanisms targeting the genes encoding digestive enzymes, gut barrier functions and antioxidant potential of broiler chickens was evidenced. Four equal broiler groups were fed 4 basal diets fortified with LEOs (oregano, cinnamon, and clove) at the levels of 0, 200, 300, and 400 mg/kg diet. Our findings revealed significant improvement in body weight gain and feed conversion ratio of birds fed higher levels of LEOs. These results came concurrently with increasing the activities of digestive enzymes at both serum and molecular levels and consequently nutrient digestibility (dry matter, ether extract, crude protein, and crude fiber) in these groups. Remarkably, the abundance of beneficial bacteria as well as the bacterial metabolites (valeric acid, butyric acid, propionic acid, acetic acid, and total short-chain fatty acids) was increased, while that of pathogenic ones was reduced following dietary inclusion of LEOs. Of note, the mRNA expression of genes encoding antioxidant stability [catalase (CAT), superoxide dismutase 1 (SOD-1), glutathione peroxidase 1 (GPX-1), nuclear factor erythroid 2-related factor 2 (NRF2), NAD(P)H dehydrogenase quinone 1 (NQO1), and heme oxygenase-1 (HO-1)] as well as barrier functions [mucin-2 (MUC-2)] and tight junction proteins, TJP [junctional adhesion molecule-2 (JAM-2) and occludin] were noticeably upregulated in broilers fortified with 400 mg/kg diet of LEOs. Overall, the present work recommended dietary inclusion of LEOs as beneficial additives for attaining targeted performance, gut health and antioxidant stability in poultry farming.

Diagnostic Efficacy of PSMA and PSCA mRNAs Combined to PSA in Prostate Cancer Patients.

BACKGROUND: Serum Prostate-specific antigen (PSA) has been used for screening and diagnosis of prostate cancer (PCa) but it is burdened by its low accuracy, creating a need for reliable diagnostic markers. Despite prostate-specific membrane antigen (PSMA) and prostate stem cell antigen (PSCA) being widely expressed in the tissue of PCa, no definite conclusion regarding their use as clinical biomarkers due to their lacking organ specificity. Therefore, this study aimed to evaluate the peripheral blood levels of PSMA and PSCA mRNAs and examine their diagnostic significance as non-invasive integrated markers.

Materials and Methods: 125 subjects were enrolled in this study. They were divided into 25 healthy controls, 25 BPH patients, and 75 PCa patients. The expression levels of PSMA and PSCA were determined using quantitative RT- PCR, in addition to measuring serum PSA.

Results: Levels of PSMA and PSCA were over-expressed in PCa patients compared to controls and BPH patients and were found to be associated with increased susceptibility to PCa. Moreover, the diagnostic values of PSMA and PSCA to distinguish PCa patients from BPH patients and controls were inferior to that of PSA. However, the combination of PSMA and PSCA with PSA enhanced the efficacy of the latter.

Conclusion: This study suggests that these genes were associated with malignant susceptibility. Concerning the duality of PSMA-PSA or PSCA-PSA, this implies the significance of their investigation together in peripheral blood of prostate patients.

Insights into growth-promoting, anti-inflammatory, immunostimulant, and antibacterial activities of Toldin CRD as a novel phytobiotic in broiler chickens experimentally infected with Mycoplasma gallisepticum.

Chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum (MG) leads to impaired broiler growth performance and significant economic losses worldwide. The utilization of essential oils (EOs) as natural alternatives to antibiotics to control CRD outbreaks is not completely clarified yet. Thus, we investigated the effect of a commercial EOs mixture (toldin CRD), in comparison to tilmicosin antibiotic, on the clinical observations, growth performance, immunity, digestive enzymes, gut barrier functions, and bacterial loads in broilers experimentally infected with MG. A total of 400 one-day-old broiler chicks were assigned into four groups; negative control (NC), positive control (PC), tilmicosin, and toldin CRD treated groups. All groups except NC were experimentally infected with MG at 14 d of age. Our data showed that birds treated with toldin CRD showed significant enhancement in the body weight gain (BWG) and feed conversion ratio (FCR) (P = 0.001 each) over the whole experimental period. Likely, improved digestibility and intestinal barrier functions in the toldin CRD treated group was evidenced by the significant upregulation (P < 0.05) of cholecystokinin (CCK), alpha 2A amylase (AMY2A), pancreatic lipase (PNLIP), junctional adhesion molecule-2 (JAM-2), occludin, and mucin-2 (MUC-2) genes. Moreover, toldin CRD exhibited immunostimulant and ant-inflammatory activities via significant downregulation (P < 0.05) of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 genes, significant reduction of lysozyme (LYZ), myeloperoxidase (MPO), and nitric oxide (NO) levels (P = 0.03, 0.02, and 0.001, respectively) and significant increase in the immunoglobulin G (IgG) level (P = 0.03). Notably, immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR) results showed prominent reductions (P < 0.05) in the levels of MG antigens and MG loads in the toldin CRD treated group, which were evidenced by relieving the clinical picture of MG experimental infection. In conclusion, we recommend the utilization of toldin CRD as a potential candidate for controlling MG infection in broiler chickens.

Exosomes Derived from BM-MSCs Mitigate the Development of Chronic Kidney Damage Post-Menopause via Interfering with Fibrosis and Apoptosis.

The rate of chronic kidney disease (CKD) is increasing globally, and it is caused by continuous damage to kidney tissue. With time the renal damage becomes irreversible, leading to CKD development. In females, post-menopause lack of estrogen supply has been described as a risk factor for CKD development, and studies targeting post-menopause CKD are scarce. In the present study, we used exosomes isolated from bone marrow mesenchymal stem/stromal cells (BM-MSCs) to test their therapeutic potential against the development of CKD. At first, the menopause model was achieved by surgical bilateral ovariectomy in female albino rats. After that, 100 µg of exosomes was given to ovariectomized rats, and the study continued for 2 months. Changes in urine volume, urine protein content, kidney function biochemical parameters (creatinine and BUN), kidney antioxidant parameters (SOD, GPx and CAT), histological changes, immunohistochemical levels of caspase 3, and the gene expression of NGAL (related to kidney damage), TGFß1 and αSMA (related to fibrosis and EMT), and caspase 3 (related to apoptosis) were studied. After the ovariectomy, the occurrence of CKD was confirmed in the rats by the drastic reduction of serum estrogen and progesterone levels, reduced urine output, increased urinary protein excretion, elevated serum creatinine and BUN, reduced GPx SOD, and CAT in kidney tissue, degenerative and fibrotic lesions in the histopathological examination, higher immunohistochemical expression of caspase 3 and increased expression of all studied genes. After exosomes administration, the entire chronic inflammatory picture in the kidney was corrected, and a near-normal kidney structure and function were attained. This study shows for the first time that BM-MSCs exosomes are potent for reducing apoptosis and fibrosis levels and, thus, can reduce the chronic damage of the kidneys in females that are in their menopause period. Therefore, MSCs-derived exosomes should be considered a valuable therapy for preserving postmenopausal kidney structure and function and, subsequently, could improve the quality of females' life during menopause.

Prognostic value of NOTCH1 and OCT4 in gastric carcinoma.

Background: NOTCH1 pathway activation has been recently described to be a key player in gastric carcinogenesis, enhance the survival and proliferation of cancer stem cells (CSCs) and mediate chemoresistance in several malignancies. Aim: This study investigated the correlation between NOTCH1 and CSC marker OCT4 (octamer binding transcription factor-4) expression and the clinicopathological properties, survival and treatment outcome in patients with gastric carcinoma (GC) receiving adjuvant chemotherapy. Materials and. Methods: NOTCH1 and OCT4 were immunohistochemically detected in 50 post-operated specimens of GC. Patients' data regarding disease-free survival (DFS), overall survival (OS), and the response to the chemotherapy was statistically analyzed. Results: NOTCH1 and OCT4 overexpression was detected in 60% and 52% of GC tissues, respectively, and that was significantly higher than the rates in adjacent non-neoplastic gastric mucosa (P < 0.05). A significant correlation was detected between overexpression of NOTCH1 and OCT4 in GC and aggressive clinicopathological features; poor differentiation (P = 0.021, P = 0.037, respectively), depth of tumor invasion (P < 0.001 for both), TNM stage (P < 0.001 for both), lymph node metastasis (P = 0.002, P = 0.003, respectively) and distant metastasis (P < 0.001 for both). NOTCH1 was positively correlated with OCT4 (P = 0.002). Survival analysis disclosed that upregulation of NOTCH1 and OCT4 was associated with worse DFS (P = 0.013, P < 0.001, respectively) and OS (P < 0.001 for both). Overexpression of NOTCH1 and OCT4 correlated with poor response to chemotherapy (P = 0.013, P = 0.005, respectively) and worse clinical outcome. Conclusion: Combined detection of these proteins might disclose even better predictive value for shorter survival and resistance to chemotherapy.

Probiotics-loaded nanoparticles attenuated colon inflammation, oxidative stress, and apoptosis in colitis.

Promising therapy is needed for treating inflammatory bowel diseases (IBD) to overcome current treatment that inefficient and associated with unnecessary health risks. Recently, the concept of incorporating natural products into nanocarriers has been intended as a promising therapy for treating IBD via modulating their stability and bioavailability. Thus, we aimed to explore the potential alleviating effects of dietary nano-supplement combined with bacillus strains (Bacillus amyloliquefaciens; BANPs) in colitis model. Rats were orally gavaged by 5% DSS and the efficacy and mechanistic actions of BANPs were evaluated by assessing the severity of clinical signs and inflammatory and apoptosis response, histopathological and immunohistochemistry examination in colonic tissues. The severity of clinical signs was successfully alleviated and fecal Lcn-2 levels, an important colitic marker, were decreased in BANPs then free BA treated groups. In contrast, inflammatory markers overexpression IL-6, IL-1ß, TNFα, COX-2, and iNOS in the colitic group were reduced more prominently in BANPs treated group, unlike free BA. The amelioration of BANPs to colon injury was also correlated with oxidative stress suppression along with restoring total antioxidant capacity. Interestingly, BANPs treatment modulated apoptotic markers as proved by downregulation of cytochrome c, and caspase-3 and upregulation of Bcl-2 and Bax than free BA. The severity of the histopathological alterations in the colon was greatly reduced in BANPs than free BA groups. Remarkably, over-expression of ki67 and IL-6 in colonic tissues were suppressed in BANPs group. These findings together highlighted the beneficial efficacy of BANPs in IBD treatment which are evidenced by colonic inflammation alleviation. Taken together, these results recommend that BANPs is a promising agent that encourages its possible therapeutic role in colitis treatment.

Mesenchymal stem-cells' exosomes are renoprotective in postmenopausal chronic kidney injury via reducing inflammation and degeneration.

Chronic kidney disease (CKD) is an important global disease its rates are increasing worldwide. CKD is caused by injuries to kidney tissue that exceeds the rate of regeneration, which with time lead to irreversible renal damage and CKD become evident. In females, diminished estrogen supply in the postmenopausal period is associated with greater risk for developing CKD. In this study we isolated exosomes from bone marrow mesenchymal stem/stromal cells (BM-MSCs) and tested their therapeutic effects on post-menopause CKD (PM-CKD) and compared their effects with BM-MSCs. The menopause model was achieved by bilateral ovariectomy in 8-months-old female albino rats, then no treatment, 2 million BM-MSCs or 100 µg of exosomes (Exo) was given intravenously in tail vein to ovariectomized rats and the study continued for 8 weeks post-ovariectomy. Changes in weight, urine volume, urine protein content, kidney function biochemical parameters (creatinine and BUN), Kidney oxidative stress (MDA), kidney antioxidant parameters (SOD, GPx and CAT), histopathological changes, immunohistochemical expression of KIM-1 and, finally, genes related to renal damage (peroxiredoxin-3, KIM-1 and ICAM-1) and inflammation (TNF-α, Cox2 and IL-6) were recorded for all study groups. Post-ovariectomy there was an increased body weight, drastic reduction of estrogen and progesterone levels, reduced urine output, increased urinary protein excretion, elevated serum creatinine and BUN, increased MDA and reduced GPx SOD, and CAT in kidney tissue, chronic inflammation, degenerative and fibrotic lesions in histopathological examination, high expression of KIM-1 immunohistochemically and changes in gene expression analyses all pointing to the development of CKD in the study rats. In the PM-CKD groups receiving BM-MSCs or Exo, the whole chronic inflammatory picture was completely reversed towards a much normal kidney structure and function. The improvements were more observable with Exo compared to BM-MSCs. Overall, our results show for the first time that exosomes isolated from BM-MSCs are more potent in reducing chronic inflammatory changes in the kidney of postmenopausal females compared to the cell-based approach using BM-MSCs. Therefore, MSCs-derived exosomes are a promising therapeutic approach for preserving postmenopausal kidney structure and function and, subsequently, should improve the quality of life of postmenopausal females.

Interactive effects of dietary quercetin nanoparticles on growth, flesh antioxidant capacity and transcription of cytokines and Aeromonas hydrophila quorum sensing orchestrating genes in Nile tilapia (Oreochromis niloticus).

Recently, the concept of incorporating natural products into nanocarriers has been intended to promote fish growth and health via modulating their stability and bioavailability. In this concern, the potential role of reformulated quercetin into nanocarriers was examined, for the first time, on Nile tilapia's performance and immunity, flesh quality and antioxidant indices and disease resistance. Five hundred fish assigned into five experimental groups with formulated diets containing quercetin nanoparticles (QT-NPs) at levels of 0, 100, 200, 300 and 400 mg/kg were challenged with Aeromonas hydrophila (A. hydrophila) after 12 weeks feeding trial. Fish final body weight gain and feed efficiency were significantly maximized in groups enriched with 300 and 400 mg/kg of QT-NPs. Significant reduction in total saturated fatty acids and an elevation in polyunsaturated fatty acids' contents were noticed in fish fed higher QT-NPs doses. The levels of Hydrogen peroxide, reactive oxygen species and malondialdehyde, the markers of meat antioxidant capacity, were reduced by higher inclusion levels of QT-NPs. Accordingly, serum activities and transcriptional levels of GSH-Px, CAT and SOD genes were increased with elevated QT-NPs levels. Immune responses mediated by upregulation of IL-10 and TGF-ß and downregulation of IL-1ß, IL-8 and TNF-α mRNA levels were found to be positively affected by QT-NPs. Dietary QT-NPs downregulated the expression of ahyI and ahyR quorum sensing genes conferring protection against A. hydrophila challenge. This study concluded that supplementation of quercetin in encapsulated nanoparticles could improve its efficacy making it as a compelling approach to improve fish performance and as a promising drug candidate against A. hydrophila virulence.

Dietary cinnamaldehyde nanoemulsion boosts growth and transcriptomes of antioxidant and immune related genes to fight Streptococcus agalactiae infection in Nile tilapia (Oreochromis niloticus).

The present study was conducted to investigate the effects of dietary cinnamaldehyde nanoemulsion (CNE) on growth, digestive activities, antioxidant and immune responses and resistance against Streptococcus agalactiae (S. agalactiae) in Nile tilapia. Four experimental diets were formulated containing CNE at levels of 0, 100, 200 and 300 mg/kg diet for 12 weeks. At the end of the experiment, all fish were challenged by S. agalactiae. The results showed that the final body weight was increased in fish groups fed 200 and 300 mg CNE/kg diet by 18.4 and 17.2% with respect to the control group. Moreover, feed conversion ratio and digestive enzymes' activities were improved in groups fed 200 and 300 then 100 mg of dietary CNE/kg diet. Groups fed CNE exhibited a significant increase in serum immune-related parameters when compared with control group. Additionally, the hypocholesterolemic effects was achieved after CNE feeding unlike the control group in a dose dependent manner. With increasing dietary CNE levels, genes expression of cytokines and antioxidant enzymes were upregulated. Less severe adverse clinical symptoms and respectable cumulative mortalities associated with S. agalactiae infection were observed in fish fed CNE. To our knowledge, this study was the first offering a protective effect of CNE against S. agalactiae infection in Nile tilapia with a maximum down-regulation of cylE and hylB virulence genes expression noticed in group fed 300 mg of CNE/kg diet (up to 0.10 and 0.19- fold, respectively). Therefore, the present study recommended that an incorporation of CNE at level of 300 mg/kg diet for Nile tilapia could promote their growth, enhance their immunity and antioxidant status and provide protection against virulent S. agalactiae.

Dual effect of selenium loaded chitosan nanoparticles on growth, antioxidant, immune related genes expression, transcriptomics modulation of caspase 1, cytochrome P450 and heat shock protein and Aeromonas hydrophila resistance of Nile Tilapia (Oreochromis niloticus).

Nowadays there is a great attention for nanotechnology in aquaculture production. It has an efficient role in nutrients and drugs delivery, ponds sterilization, water treatment and aquatic diseases reduction. Till now, there is no available data on impact of selenite-loaded chitosan nanoparticles (SeChNPs) on Nile tilapia. Hence, the current study investigated the effects of selenite-loaded chitosan nanoparticles supplementation on the growth, immune, antioxidant and apoptotic related genes as well as resistance to Aeromonas hydrophila of Nile tilapia, Oreochromis niloticus. A total of 400 fish were randomly divided into four groups, and each group retained five replicates. The control group was fed a basal diet (with inorganic se), other groups fed diets supplemented with SeChNPs 0.5, 1 and 2 g/kg diet. The loading concentration of Se to ChNPs was 0.3, 0.6 and 1.2 mg/0.5, 1 and 2 gm respectively. Fish groups fed SeChNPs (0.5 and 1 g/kg) exhibited the highest final body gain, better feed utilization. Additionally, the expression of myostatin gene was down-regulated by 0.2 and 0.3 fold in group fed 0.5 and 1 g/kg SeChNPs when compared with control group. Dietary inclusion of SeChNPs increased serum lysozyme, alternative complement and myeloperoxidase activities and immunoglobulin type M level. Supplementation of SeChNPs at the level of 2 g/kg up-regulated glutathione peroxidase, superoxide dismutase and catalase expression by 1.12, 4.9 and 2.31 folds respectively, in comparison with control group. In contrast, the levels of C- reactive protein and malondialdehyde were reduced. The expression of IL-10, IL-8, TNF-α and IL-1ß genes was up-regulated after dietary inclusion of different levels of SeChNPs in a dose dependent manner. Post-challenge, the highest survival rate was detected in group fed 2 g/kg SeChNPs (93%) in contrast, the control group was displayed the lowest survival rate (45%). After challenge with A. hydrophila, the expression of caspase 1 was up-regulated in groups fed 1 and 2 g/kg of SeChNPs. Moreover, the maximum down-regulation of cytochromes P450 and heat shock protein were found in 2 g/kg SeChNPs supplemented group (reduced by 0.4 and 0.6-fold, respectively, when compared with control group). In conclusion, the ameliorative effects of SeChNPs on Nile tilapia growth resulted from immune stimulatory and free radicals scavenging effects of selenium loaded chitosan nano composite.

Knowledge, awareness, and practice of breast self-examination among females in Mosul city, Iraq.

AIMS: This study is carried out to report on the knowledge and practice regarding breast self-examination (BSE) among women from the city of Mosul in Iraq and to evaluate the prevalence of performing clinical breast examination (CBE) and mammography among them. SETTINGS AND DESIGN: A descriptive, cross-sectional survey carried out among females working in the University of Mosul, as a sample of the female population of Mosul city. SUBJECTS AND METHODS: The sample was collected conveniently, and the data were collected from July to November 2018. Data were collected by interviews with 405 participants. Knowledge answers were scored and categorized into two groups: good and poor level of knowledge. RESULTS: A final sample of 384 participants were included in the analysis, with a mean age of 42.58 ± 8.9. Only 39 (10.1%) and 37 (9.6%) participants performed mammographic examination and CBE of their breasts, respectively. Just 100 (30.3%) of the 330 females who knew BSE performed BSE routinely or intermittently. The mean knowledge score was 4.22 ± 1.66, and only 141 females (42.7%) were found to have a good level of knowledge. A statistically significant association of knowledge level with marital status (P = 0.015), perceived benefit of BSE (P = 0.001), previous gain of instructions of BSE (P < 0.05), and the provider (P < 0.05) was found. CONCLUSIONS: The performance results of BSE were poor as well as for CBE and mammography among the study participants. There is a need for educational programs to create awareness and improve knowledge about routine breast cancer screening behavior.

ERCC1, PARP-1, and AQP1 as predictive biomarkers in colon cancer patients receiving adjuvant chemotherapy.

BACKGROUND: The recognition of high-risk colon cancer patients prone to chemoresistant and recurrent disease is a challenge. OBJECTIVES: We aimed to assess the immunohistochemical expression of ERCC1, PARP-1, and AQP1 in 60 cases of stage II and III colon cancer who underwent curative resection and adjuvant chemotherapy. Their predictive role of tumor progression and disease-free survival (DFS) was analyzed. METHODS: The immunohistochemical expression of ERCC1, PARP-1, and AQP1 in 60 cases of stage II and III colon cancer who underwent curative resection and adjuvant chemotherapy was studied. The collected data on the overall survival (OS), disease-free survival (DFS), and the response to the chemotherapy were analyzed. RESULTS: Positive nuclear ERCC1 expression was identified in 58.3% of the patients, ERCC1 expression was significantly associated with left-sided tumors (P< 0.01). Moreover, its expression was significantly associated with the aggressive tumor characteristics including high grade, lymph node metastasis and advanced tumor stage (P< 0.001 for each). High nuclear PARP-1 expression was observed in 63.3% of the cases, and its expression was significantly associated with tumor grade and lymph node metastasis (P= 0.003 for each). Positive membranous AQP1 expression was identified in 41.7% of patients, and it was associated with high grade, lymph node metastasis and advanced tumor stage (P< 0.001 for each). During the follow-up period, 23 patients (38.3%) exhibited a tumor progression; this was significantly associated with positive ERCC1, high PARP-1, and negative AQP1 expression. Statistics of the survival data revealed that shorter DFS was significantly associated with positive ERCC1, high PARP-1, and positive AQP1 expression (P= 0.005, 0.016, 0.002, respectively). CONCLUSIONS: ERCC1, PARP1, and AQP1 are adverse prognostic biomarkers in stage II-III colon cancer. Moreover, adjuvant chemotherapy may not be beneficial for patients with positive ERCC1, high PARP1, and AQP1-negative tumors. Therefore, we recommend that ERCC1, PARP-1, and AQP1 should be assessed during the selection of the treatment strategy for stage II-III colon cancer patients.