Probiotic-derived silver nanoparticles target mTOR/MMP-9/BCL-2/dependent AMPK activation for hepatic cancer treatment.

Recent advances in nanotechnology have offered novel ways to combat cancer. By utilizing the reducing capabilities of Lactobacillus acidophilus, silver nanoparticles (AgNPs) are synthesized. The anti-cancer properties of AgNPs have been demonstrated in previous studies against several cancer cell lines; it has been hypothesized that these compounds might inhibit AMPK/mTOR signalling and BCL-2 expression. Consequently, the current research used both in vitro and in silico approaches to study whether Lactobacillus acidophilus AgNPs could inhibit cell proliferation autophagy and promote apoptosis in HepG2 cells. The isolated strain was identified as Lactobacillus acidophilus strain RBIM based on 16 s rRNA gene analysis. Based on our research findings, it has been observed that this particular strain can generate increased quantities of AgNPs when subjected to optimal growing conditions. The presence of silanols, carboxylates, phosphonates, and siloxanes on the surface of AgNPs was confirmed using FTIR analysis. AgNPs were configured using UV-visible spectroscopy at 425 nm. In contrast, it was observed that apoptotic cells exhibited orange-coloured bodies due to cellular shrinkage and blebbing initiated by AgNP treatment, compared to non-apoptotic cells. It is worth mentioning that AgNPs exhibited remarkable selectivity in inducing cell death, specifically in HepG2 cells, unlike normal WI-38 cells. The half-maximum inhibitory concentration (IC50) values for HepG2 and WI-38 cells were 4.217 µg/ml and 154.1 µg/ml, respectively. AgNPs induce an upregulation in the synthesis of inflammation-associated cytokines, including (TNF-α and IL-33), within HepG2 cells. AgNPs co-treatment led to higher glutathione levels and activating pro-autophagic genes such as AMPK.Additionally, it resulted in the suppression of mTOR, MMP-9, BCL-2, and α-SMA gene expression. The docking experiments suggest that the binding of AgNPs to the active site of the AMPK enzyme leads to inhibiting its activity. The inhibition of AMPK ultimately results in the suppression of the mechanistic mTOR and triggers apoptosis in HepG2 cells. In conclusion, the results of our study indicate that the utilization of AgNPs may represent a viable strategy for the eradication of liver cancerous cells through the activation of apoptosis and the enhancement of immune system reactions.

Dietary lysozyme and avilamycin modulate gut health, immunity, and growth rate in broilers.

BACKGROUND: Attempts to use dietary lysozyme (LYZ) as an alternative to antibiotics in broilers have been successful, but further research is needed for effective use. Here, we compared the differences between LYZ and avilamycin (AVI) feed additives for growth performance, gut health and immunity of broilers. One-day old, one hundred and twenty broiler chicks (Ross 308) were randomly allocated into three groups consisting forty birds in each group. Standard diet without supplementation was applied as the control group (I), while the chicks of the other groups were supplemented with 100 mg of AVI per kg diet (AVI, group II), and 90 mg LYZ per kg diet (LYZ, group III) for five consecutive weeks. RESULTS: Body weight, feed conversion ratio, body weight gain, and European production efficiency factor were markedly (p < 0.05) increased in both AVI and LYZ groups in relation to CON group, but the feed intake and protein efficiency ratio were not affected. Both AVI and LYZ significantly (p < 0.001) upregulated the mRNA expression of ileal interleukin-18 (IL-18), interferon-gamma (IFN-γ), and interleukin-10 (IL-10), interleukin-2 (IL-2), and glutathione peroxidase (GSH-PX) genes compared to CON group. However, IL-2, IL-10, IL-18, and GSH-PX genes were markedly (p < 0.01) upregulated in LYZ compared to the AVI group. LYZ treated group had a significant increase (p < 0.05) in the serological haemagglutination inhibition titers of H5N1 vaccination and a significant decrease (p < 0.0001) in coliform counts compared to control and AVI groups, but all growth parameters were nearly similar between AVI and LYZ groups. The VH and VH/CD were markedly higher in LYZ than AVI and control groups. CONCLUSION: Exogenous dietary lysozyme supplementation by a dose of 90 mg/kg broilers' diet induced better effects on intestinal integrity, fecal bacterial counts, immune response, and growth performance which were comparable to avilamycin. Therefore, dietary lysozyme could safely replace avilamycin in the broiler chickens' diet. However, further experimental studies regarding the use of lysozyme in commercial broilers, both in vitro and in vivo, targeting more communities of intestinal microbiome and explaining more details about its beneficial effects need to be conducted.

Bioefficacy of dietary inclusion of Nannochloropsis oculata on Eimeria spp. challenged chicks: clinical approaches, meat quality, and molecular docking.

Although anticoccidial drugs have been used to treat avian coccidiosis for nearly a century, resistance, bird harm, and food residues have caused health concerns. Thus, Nannochloropsis oculata was investigated as a possible coccidiosis treatment for broilers. A total of 150 1-day-old male Cobb broiler chicks were treated as follows: G1-Ng: fed a basal diet; G2-Ps: challenged with Eimeria spp. oocysts and fed basal diet; G3-Clo: challenged and fed basal diet with clopidol; G4-NOa: challenged and fed 0.1% N. oculata in diet, and G5-NOb: challenged and fed 0.2% N. oculata. Compared to G2-Ps, N. oculata in the diet significantly (P < 0.05) decreased dropping scores, lesion scores, and oocyst shedding. Without affecting breast meat colour metrics, N. oculata improved meat quality characters. At 28 days of age, birds received 0.2% N. oculata had significantly (P < 0.05) higher serum levels of MDA, T-SOD, HDL, and LDL cholesterol compared to G2-Ps. Serum AST, ALT, and urea levels were all decreased when N. oculata (0.2%) was used as opposed to G2-Ps. Histopathological alterations and the number of developmental and degenerative stages of Eimeria spp. in the intestinal epithelium were dramatically reduced by 0.2% N. oculata compared to G2-Ps. Molecular docking revealed a higher binding affinity of N. oculata for E. tenella aldolase, EtAMA1, and EtMIC3, which hindered glucose metabolism, host cell adhesion, and invasion of Eimeria. Finally, N. oculata (0.2%) can be used in broiler diets to mitigate the deleterious effects of coccidiosis.

Panax ginseng ameliorates hepatorenal oxidative alterations induced by commercially used cypermethrin in male rats: experimental and molecular docking approaches.

Cypermethrin (CYP) is a synthetic pyrethroid utilized as an insecticide in agriculture and various pest eradication programs. However, it induces numerous health hazards for animals and humans. Therefore, the current study used Panax ginseng root extract (ginseng) to reduce the hepatorenal damage caused by commercially used CYP. Thirty-two male Wistar albino rats were distributed into control, ginseng (300 mg/kg B.W/day), CYP (4.67 mg/kg B.W.), and Ginseng+CYP (rats received both CYP and ginseng). All treatments were administered orally for 30 consecutive days. Cypermethrin induced harmful effects on hepatic and renal tissues through a substantial decline in body weight in addition to a considerable increase in liver enzymes, functional renal markers, and cholesterol. Also, CYP significantly decreased acetylcholinesterase (AChE) activity and increased pro-inflammatory cytokines (interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α)). Moreover, a marked increase in malondialdehyde level with a significant drop in reduced glutathione level and total superoxide dismutase (T-SOD) and catalase (CAT) activities was reported in the CYP group in kidney and liver tissues. Additionally, CYP exhibited affinities to bind and inhibit AChE and antioxidant enzymes (T-SOD and CAT) in rats following the molecular docking modeling. The apparent hepatorenal oxidative damage was linked with obvious impairments in the liver and kidney histoarchitecture, immunohistochemical staining of B cell lymphoma-2 (Bcl-2), and caspase-3 proteins. Ginseng reduced CYP's oxidative alterations by repairing the metabolic functional markers, improving antioxidant status, reducing the inflammatory response, and enhancing the molecular docking evaluation. It also ameliorated the intensity of the histopathological alterations and improved the immunohistochemical staining of Bcl-2 and caspase-3 proteins in the liver and kidney tissues. Finally, concomitant oral administration of ginseng mitigated CYP-prompted hepatorenal damage through its antioxidant, anti-inflammatory, and anti-apoptotic potentials.

Rutin attenuates D-galactose-induced oxidative stress in rats' brain and liver: molecular docking and experimental approaches.

Oxidative stress results from the imbalance between reactive oxygen species (ROS) production and antioxidant defence and is primarily involved in aging. The current study investigated the antioxidant activity of rutin in aging in rats induced by D-galactose (D-gal) for 42 days. Rutin was orally used at doses of 50 and 100 mg kg-1 daily. Results showed that D-gal induced oxidative alterations in the brain and liver recognized via upregulation of aging and oxidative markers. In contrast, rutin ameliorated the oxidative stress induced by D-gal by enhancing antioxidant markers such as superoxide dismutase-1, glutathione peroxidase-1, and glutathione S-transferase-α. Also, rutin significantly decreased the accumulation of ß-galactosidase and reduced the expression of p53, p21, Bcl-2-associated X protein (Bax), caspase-3 (CASP3), and mammalian target of rapamycin (mTOR) in brain and hepatic tissues. Rutin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Moreover, rutin markedly reduced the increased immunohistochemical expression of ß-galactosidase, 8-hydroxy-2'-deoxyguanosine, calcium-binding adapter molecule 1, glial fibrillary acidic protein, Bax, and interleukin-6 and significantly increased Bcl2, synaptophysin, and Ki67. Furthermore, a molecular docking study revealed that rutin exhibited high affinity to rat and human caspases, PI3K/AKT/mTOR, and the IL-6 receptor. Finally, we can conclude that rutin supplementation can be a promising natural protective compound that could delay aging and maintain health.

Thymoquinone, piperine, and sorafenib combinations attenuate liver and breast cancers progression: epigenetic and molecular docking approaches.

BACKGROUND: Traditional herbal medicine has been used for centuries to cure many pathological disorders, including cancer. Thymoquinone (TQ) and piperine (PIP) are major bioactive constituents of the black seed (Nigella sativa) and black pepper (Piper nigrum), respectively. The current study aimed to explore the potential chemo-modulatory effects, mechanisms of action, molecular targets, and binding interactions after TQ and PIP treatments and their combination with sorafenib (SOR) against human triple-negative breast cancer (MDA-MB-231) and liver cancer (HepG2) cells. METHODS: We determined drug cytotoxicity by MTT assay, cell cycle, and death mechanism by flow cytometry. Besides, the potential effect of TQ, PIP, and SOR treatment on genome methylation and acetylation by determination of DNA methyltransferase (DNMT3B), histone deacetylase (HDAC3) and miRNA-29c expression levels. Finally, a molecular docking study was performed to propose potential mechanisms of action and binding affinity of TQ, PIP, and SOR with DNMT3B and HDAC3. RESULTS: Collectively, our data show that combinations of TQ and/or PIP with SOR have significantly enhanced the SOR anti-proliferative and cytotoxic effects depending on the dose and cell line by enhancing G2/M phase arrest, inducing apoptosis, downregulation of DNMT3B and HDAC3 expression and upregulation of the tumor suppressor, miRNA-29c. Finally, the molecular docking study has identified strong interactions between SOR, PIP, and TQ with DNMT3B and HDAC3, inhibiting their normal oncogenic activities and leading to growth arrest and cell death. CONCLUSION: This study reported TQ and PIP as enhancers of the antiproliferative and cytotoxic effects of SOR and addressed the mechanisms, and identified molecular targets involved in their action.

Cancer metabolism control by natural products: Pyruvate kinase M2 targeting therapeutics.

Glycolysis is the primary source of energy for cancer growth and metastasis. The shift in metabolism from mitochondrial oxidative phosphorylation to aerobic glycolysis is called the Warburg effect. Cancer progression due to aerobic glycolysis is often associated with the activation of oncogenes or the loss of tumor suppressors. Therefore, inhibition of glycolysis is one of the effective strategies in cancer control. Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme overexpressed in breast, prostate, lung, colorectal, and liver cancers. Here, we discuss published studies regarding PKM2 inhibitors from natural products that are promising drug candidates for cancer therapy. We have highlighted the potential of natural PKM2 inhibitors for various cancer types. Moreover, we encourage researchers to evaluate the combinational effects between natural and synthetic PKM2 inhibitors. Also, further high-quality studies are needed to firmly establish the clinical efficacy of natural products.

Curcumin and Thymoquinone Combination Attenuates Breast Cancer Cell Lines' Progression.

Breast cancer is the most harmful malignancy in women worldwide. Therefore, in the current study, we investigated the combinatory effect of natural bioactive compounds, including curcumin (Cur) and thymoquinone (TQ), on MCF7 and MDA-MB-231 breast cancer cell lines' progression. We investigated the Fa values and combination index of Cur and TQ in this context. Moreover, cytotoxicity percentages, annexin-V, proliferation, colony formation, and migration assays were used along with cell cycle analysis. In addition, caspase-3, phosphatidylinositol 3-kinase (PI3K), and protein kinase B (AKT) protein levels were determined by ELISA assessment. The results showed that Cur, TQ, and Cur + TQ induced apoptosis with cell cycle arrest and decreased cell proliferation, colony formation, and migration activities. Cur + TQ combination significantly increased caspase-3 and decreased PI3K and AKT protein levels. These results suggest the promising anticancer benefit of the Cur and TQ combination against breast cancer.

Potential therapeutic interventions of plant-derived isoflavones against acute lung injury.

Acute lung injury (ALI) is a life-threatening syndrome that possibly leads to high morbidity and mortality as no therapy exists. Several natural ingredients with negligible adverse effects have recently been investigated to possibly inhibit the inflammatory pathways associated with ALI at the molecular level. Isoflavones, as phytoestrogenic compounds, are naturally occurring bioactive compounds that represent the most abundant category of plant polyphenols (Leguminosae family). A broad range of therapeutic activities of isoflavones, including antioxidants, chemopreventive, anti-inflammatory, antiallergic and antibacterial potentials, have been extensively documented in the literature. Our review exclusively focuses on the possible anti-inflammatory, antioxidant role of botanicals'-derived isoflavones against ALI and their immunomodulatory effect in experimentally induced ALI. Despite the limited scope covering their molecular mechanisms, isoflavones substantially contributed to protecting from ALI via inhibiting toll-like receptor 4 (TLR4)/Myd88/NF-κB pathway and subsequent cytokines, chemokines, and adherent proteins. Nonetheless, future research is suggested to fill the gap in elucidating the protective roles of isoflavones to alleviate ALI concerning antioxidant potentials, inhibition of the inflammatory pathways, and associated molecular mechanisms.

Thymoquinone and Costunolide Induce Apoptosis of Both Proliferative and Doxorubicin-Induced-Senescent Colon and Breast Cancer Cells.

Doxorubicin (Dox) induces senescence in numerous cancer cell types, but these senescent cancer cells relapse again if they are not eliminated. On this principle, we investigated the apoptotic effect of thymoquinone (TQ), the active ingredient of Nigella sativa seeds and costunolide (COS), the active ingredient of Costus speciosus, on the senescent colon (Sen-HCT116) and senescent breast (Sen-MCF7) cancer cell lines in reference to their corresponding proliferative cells to rapidly eliminate the senescent cancer cells. The senescence markers of Sen-HCT116 and Sen-MCF7 were determined by a significant decrease in bromodeoxyuridine (BrdU) incorporation and significant increases in SA-ß-gal, p53, and p21 levels. Then proliferative, Sen-HCT116, and Sen-MCF7 cells were subjected to either TQ (50 µM) or COS (30 µM), the Bcl2-associated X protein (Bax), B-cell lymphoma 2 (Bcl2), caspase 3 mRNA expression and its activity were established. Results revealed that TQ significantly increased the Bax/Bcl2 ratio in HCT116 + Dox5 + TQ, MCF7 + TQ, and MCF7 + Dox5 + TQ compared with their corresponding controls. COS significantly increased the Bax/Bcl2 ratio in HCT116 + Dox5 + TQ and MCF7 + Dox5 + TQ compared with their related controls. Also, TQ and COS were significantly increased caspase 3 activity and cell proliferation of Sen-HCT116 and Sen-MCF7. The data revealed a higher sensitivity of senescent cells to TQ or COS than their corresponding proliferative cells.

Therapeutic Potential of Thymoquinone and Its Nanoformulations in Pulmonary Injury: A Comprehensive Review.

As a crucial organ, the lung is exposed to various harmful agents that may induce inflammation and oxidative stress, which may cause chronic or acute lung injury. Nigella sativa, also known as black seed, has been widely used to treat various diseases and is one of the most extensively researched medicinal plants. Thymoquinone (TQ) is the main component of black seed volatile oil and has been proven to have antioxidant, anti-inflammatory, and antineoplastic properties. The potential therapeutic properties of TQ against various pulmonary disorders have been studied in both in vitro and in vivo studies. Furthermore, the application of nanotechnology may increase drug solubility, cellular absorption, drug release (sustained or control), and drug delivery to lung tissue target sites. As a result, fabricating TQ as nanoparticles (NPs) is a potential therapeutic approach against a variety of lung diseases. In this current review, we summarize recent findings on the efficacy of TQ and its nanotypes in lung disorders caused by immunocompromised conditions such as cancer, diabetes, gastric ulcers, and other neurodegenerative diseases. It is concluded that TQ nanoparticles with anti-inflammatory, antioxidant, antiasthma, and antitumor activity may be safely applied to treat lung disorders. However, more research is required before TQ nanoparticles can be used as pharmaceutical preparations in human studies.

Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats' Brain and Heart.

D-galactose (D-gal) administration causes oxidative disorder and is widely utilized in aging animal models. Therefore, we subcutaneously injected D-gal at 200 mg/kg BW dose to assess the potential preventive effect of thymoquinone (TQ) and curcumin (Cur) against the oxidative alterations induced by D-gal. Other than the control, vehicle, and D-gal groups, the TQ and Cur treated groups were orally supplemented at 20 mg/kg BW of each alone or combined. TQ and Cur effectively suppressed the oxidative alterations induced by D-gal in brain and heart tissues. The TQ and Cur combination significantly decreased the elevated necrosis in the brain and heart by D-gal. It significantly reduced brain caspase 3, calbindin, and calcium-binding adapter molecule 1 (IBA1), heart caspase 3, and BCL2. Expression of mRNA of the brain and heart TP53, p21, Bax, and CASP-3 were significantly downregulated in the TQ and Cur combination group along with upregulation of BCL2 in comparison with the D-gal group. Data suggested that the TQ and Cur combination is a promising approach in aging prevention.

Quercetin Attenuates Brain Oxidative Alterations Induced by Iron Oxide Nanoparticles in Rats.

Iron oxide nanoparticle (IONP) therapy has diverse health benefits but high doses or prolonged therapy might induce oxidative cellular injuries especially in the brain. Therefore, we conducted the current study to investigate the protective role of quercetin supplementation against the oxidative alterations induced in the brains of rats due to IONPs. Forty adult male albino rats were allocated into equal five groups; the control received a normal basal diet, the IONP group was intraperitoneally injected with IONPs of 50 mg/kg body weight (B.W.) and quercetin-treated groups had IONPs + Q25, IONPs + Q50 and IONPs + Q100 that were orally supplanted with quercetin by doses of 25, 50 and 100 mg quercetin/kg B.W. daily, respectively, administrated with the same dose of IONPs for 30 days. IONPs induced significant increases in malondialdehyde (MDA) and significantly decreased reduced glutathione (GSH) and oxidized glutathione (GSSG). Consequently, IONPs significantly induced severe brain tissue injuries due to the iron deposition leading to oxidative alterations with significant increases in brain creatine phosphokinase (CPK) and acetylcholinesterase (AChE). Furthermore, IONPs induced significant reductions in brain epinephrine, serotonin and melatonin with the downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (mtTFA) mRNA expressions. IONPs induced apoptosis in the brain monitored by increases in caspase 3 and decreases in B-cell lymphoma 2 (Bcl2) expression levels. Quercetin supplementation notably defeated brain oxidative damages and in a dose-dependent manner. Therefore, quercetin supplementation during IONPs is highly recommended to gain the benefits of IONPs with fewer health hazards.

Pomegranate (Punica granatum) Fruit Extract Suppresses Cancer Progression and Tumor Angiogenesis of Pancreatic and Colon Cancer in Chick Chorioallantoic Membrane Model.

Pomegranate fruit extract contains many polyphenols and flavonoids of diverse biological importance including anticancer potential. In cancer, the angiogenesis process facilitates solid cancer growth and metastasis. Here, the antiangiogenic effect of pomegranate fruit extract against human pancreatic cancer (Suit-2) and colon (colo205) cell lines in the chick chorioallantoic membrane (CAM) model was studied along with the effect of pomegranate fruit extract on fibroblast growth factor (FGF2). Pomegranate fruit extract significantly reduced the tumor weight and hemoglobin content in CAM models of pancreatic Suit-2 and colon colo205.

Transcriptomic and biochemical effects of pycnogenol in ameliorating heat stress-related oxidative alterations in rats.

BACKGROUND: Heat stress is a condition that is due to extreme heat exposure. It occurs when the body cannot keep its temperature healthy in response to a hot climate and associated with oxidative stress. Testicular hyperthermia can induce apoptosis of sperm cells, affect sperm production and decrease sperm concentration, leading to sperm disorder, for this reason, we examined the protective impact of pycnogenol that it has a wide range of biological benefits, including antioxidant, anti-inflammatory and anti-cancer activities against the oxidative alterations that happen in testicular and brain tissues due to heat stress in rats. STUDY DESIGN: Forty-eight Wistar male rats, approximately around 6 weeks age were allocated randomly into four groups (12 in each) of control, HS (subjected to heat stress and supplemented orally with 50 mg of pycnogenol/kg b. w./day dissolved in saline for 21 days), and pycnogenol (rats supplemented orally with 50 mg of pycnogenol/kg b. w./day dissolved in saline for 21 days). RESULTS: Data revealed a promising role of pycnogenol as an antioxidant, natural product to successfully reverse the heat-induced oxidative alterations in testicular and brain tissues of rats through significant upregulation of superoxide dismutase-2, catalase, reduced glutathione, and anti-apoptotic gene, while downregulating pro-apoptotic, and heat shock protein70. Pycnogenol treatment also reversed the reproductive hormone level and spermatogenesis to their normal values. CONCLUSION: Pycnogenol as a natural protective supplement could recover these heat stress-induced oxidative changes in testes and hypothalamus.

Nanoformulated Ajwa (Phoenix Dactylifera) Bioactive Compounds Improve the Safety of Doxorubicin without Compromising its Anticancer Efficacy in Breast Cancer.

One of the major causes of women's death in the world is breast cancer. Consequently, numerous regimens for the control of this severe disease have been created. The chemotherapeutic agent doxorubicin (DOX) is frequently used to treat breast cancer, but DOX can also cause cardiotoxic effects that lead to heart failure. Therefore, many research studies have been done to find a natural product that effectively potentiates or does not interfere with DOX's anticancer effect and protects against its cardiotoxicity. We studied the impact of combined nanoformulated Ajwa (Phoenix dactylifera) selected bioactive compounds (BAC) rutin (R) and quercetin (Q) in nude mice breast cancer xenografts on DOX-mediated anticancer efficacy. We also studied if this Ajwa BAC could safeguard against DOX-mediated cardiomyopathies by evaluating plasma cardiac troponin-I (cTn-I) levels and cardiac histopathology. Nanoformulated Ajwa BAC effectively alleviated weight loss induced by DOX in mice and significantly decreased the elevated cTn-I. Furthermore, 5 mg RQ-NPs/kg of nude mice that subcutaneously daily injected for 11 days, attenuated the histopathological alterations induced in cardiac muscles due to DOX without any interference with the anticancer effects of DOX against breast cancer.

ß-glucan administration improves growth performance and gut health in New Zealand White and APRI rabbits with different breed responses.

This study investigated the effects of oral administration of ß-glucan 1,3 (pharmaceutical grade 10%) on growth performance and carcass traits in two breeds of weanling rabbits adapted to survive in Egypt, New Zealand White (NZW) and Animal Production Research Institute (APRI) rabbits, with special attention to relative mRNA expression of interleukins and antioxidant enzyme genes, biochemical, and histological alterations. Oral administration of ß-glucan with doses 0.25 and 0.5 ml per one-liter of drinking water significantly accelerated body weight gain (BWG) in both rabbits' breeds, reduced total feed consumption (FC), and reduced feed conversion ratio (FCR), especially the 0.5 ml per one-liter dose in both rabbit breeds. There are remarkable differences in all the growth performance traits due to breed effect. The interaction effect between ß-glucan and breed significantly improved BWG, FC, and FCR. There were non-significant differences in all carcass traits studied due to oral administration of ß-glucan with both doses, except in dressing percentages. The highest of the dressing percentages were observed at doses 0.25 ml per one-liter (51%) and 0.5 ml per one-liter (52%) compared with control (50%). Our findings show significant variations in the final BW, total daily gain, feed consumption, and total feed conversion ratio between NZW and APRI rabbits. Absence of significant differences in the hot carcass weight and dressing percentage between the genetic groups had been reported in this study. Supplementing NZW and APRI rabbits with ß-glucan increased blood total protein and globulin. The duodenal villi dimensions, splenic lymphoid diameter, muscular fiber diameter, and muscular glycogen areas were significantly increased by ß-glucan administration. Expression of intestinal interleukin-18 (IL-18) in NZW rabbits treated with 0.25 and 0.5 doses of ß-glucan was significantly upregulated and enhanced the immune response. ß-glucan upregulated the expression of intestinal occludin mRNA particularly at dose 0.5 ß-glucan as well as upregulated intestinal superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPx1), which modulates anti-inflammatory and antioxidant properties. In conclusion, oral administration of ß-glucan at a dose of 0.25 or 0.5 ml per one-liter drinking water provided beneficial effects in the growth performance and health status of rabbits.

Thymoquinone-chemotherapeutic combinations: new regimen to combat cancer and cancer stem cells.

Cancer is a worldwide disease that causes millions of cases of mortality and morbidity. The major problem associated with the cancer is its resistance to conventional therapy and a high relapse rate. The use of chemotherapy to treat cancer began at the start of the twentieth century with attempts to control cancer. In time advance, many cancer chemotherapeutic agents have been developed for cancer treatment with different mechanisms of action including the alkylating agents, antimetabolites, antimicrotubule, topoisomerase inhibitors, and cytotoxic antibiotics, all of which have toxic effects toward normal cells in the body. Here, we reviewed chemotherapeutics' anticancer role potentiation and safety by thymoquinone (TQ) alone or in combination with the most common therapeutic drugs. Our search was done through PubMed, Science Direct, Springer Link, Taylor & Francis Online, Wiley Online Library, Nature publication group, SAGE Journals, and Web of Science databases. We recognized that TQ-chemotherapeutics combination increased chemo-modulation to the anticancer effect of different chemotherapeutics and protected the normal body cells from the toxic injuries that are induced by chemotherapeutics based on its antioxidant power. Moreover, the current study investigates the possible combinatory effect of TQ and chemotherapeutics to control cancer stem cells through molecular docking targeting of wingless/integrated (Wnt) and Hedgehog (Hh). We found that TQ modulates the Wnt and Hh pathways, by binding with tankyrase-2 and smoothened 7TM receptor, respectively, more efficiently than most chemotherapeutics drugs, while methotrexate showed high-binding affinity compared with TQ. Therefore, we encourage researchers to investigate the chemo-modulatory potential and protective effects of TQ in combination with chemotherapeutics for either cancer or cancer stem cell treatment.

Senescent Colon and Breast Cancer Cells Induced by Doxorubicin Exhibit Enhanced Sensitivity to Curcumin, Caffeine, and Thymoquinone.

Cellular senescence is a process of physiological growth arrest that can be induced by intrinsic or extrinsic stress signals. Some cancer therapies are associated with senescence of cancer cells with a typical cell cycle arrest. Doxorubicin (Dox) induces senescence by a p53-dependent pathway and telomere dysfunction of numerous cancers. However, cellular senescence induces suppression in proliferation activity, and these cells will remain metabolically active and play an important role in tumor relapse and development of drug resistance. In the current study, we investigated the apoptotic effect of curcumin (Cur), caffeine (Caff), and thymoquinone (TQ) on senescent colon cancer HCT116 and breast cancer MCF7 cell lines treated with Dox. Results showed typical senescence markers including decreased bromodeoxyuridine incorporation, increased accumulation of senescence-associated ß-galactosidase (SA-ß-gal), cell cycle arrest, and upregulation of p53, P-p53, and p21 proteins. Annexin-V analysis by flow cytometry revealed 2- to 6-fold increases in annexin-V-positive cells in Dox-treated MCF7 and HCT116 cells by Cur (15 µM), Caff (10 mM), and TQ (50 µM; P < .001). In comparison between proliferative and senescent of either HCT116 or MCF7 cells, Caff at 15 mM and TQ at 25 µM induced significant increases in apoptosis of Dox-treated cells compared with proliferative cells (P < .001). Data revealed that Cur, Caff, and TQ potentially induced apoptosis of both proliferative and senescent HCT116 and MCF7 cells. In vivo and clinical trials are of great importance to validate this result.

Impact of garlic (Allium sativum) oil on cisplatin-induced hepatorenal biochemical and histopathological alterations in rats.

Cisplatin (cis-diamminedichloridoplatinum II [CDDP]) is a chemotherapeutic agent used for treating different cancers types. However, its usage is limited because it induces harmful toxicities in multiple organs, including nephrotoxicity and hepatotoxicity. Garlic oil (GO) has several pharmacological activities, including antioxidant activity. The aim of the study is to evaluate the protective and antioxidant effects of GO against CDDP-induced acute liver and kidney injuries in male rats. CDDP-treated rats showed increased serum ALT, AST, ALP, LDH, uric acid, urea, creatinine, and IL-6 levels. Moreover, CDDP-treated rats showed significantly increased MDA and NO levels and decreased GSH level and T.SOD and CAT activities in hepatic and renal tissues compared with control rats. GO administration, especially at a dose of 100 ml/kg, alleviated CDDP-induced adverse biochemical and histopathological alterations and restored them to their normal values. These results suggest that GO reverses CDDP-induced hepatorenal damage by exerting antioxidant and anti-inflammatory effects.