Bladder cancer: therapeutic challenges and role of 3D cell culture systems in the screening of novel cancer therapeutics.

Bladder cancer (BC) is the sixth most common worldwide urologic malignancy associated with elevated morbidity and mortality rates if not well treated. The muscle-invasive form of BC develops in about 25% of patients. Moreover, according to estimates, 50% of patients with invasive BC experience fatal metastatic relapses. Currently, resistance to drug-based therapy is the major tumble to BC treatment. The three-dimensional (3D) cell cultures are clearly more relevant not only as a novel evolving gadget in drug screening but also as a bearable therapeutic for different diseases. In this review, various subtypes of BC and mechanisms of drug resistance to the commonly used anticancer therapies are discussed. We also summarize the key lineaments of the latest cell-based assays utilizing 3D cell culture systems and their impact on understanding the pathophysiology of BC. Such knowledge could ultimately help to address the most efficient BC treatment.

Quercetin: Putative effects on the function of cryopreserved sperms in domestic animals.

Quercetin is one of the most used antioxidant flavonoids and largely exists in many fruits and vegetables because of its capability to scavenge the free reactive oxygen species (ROSs) by repressing lipid peroxy radical fusion, metal ion chelating through enzyme inhibition, and adopting the repair mechanisms. It also exhibits various biological actions, including antioxidative, anti-inflammatory and antimicrobial activities. Furthermore, it contributes well to sustaining the endogenous cellular antioxidant defence system. The process of cryopreservation is associated with increased oxidative stress, and some steps are potential sources of ROSs, including the method of semen collection, handling, cryopreservation culture media, and thawing, which result in impaired sperm function. Several antioxidants have been proposed to counteract the harmful impact of ROS during semen cryopreservation. The antioxidant capability of quercetin has been verified in different animal species for providing valuable defence to sperm during the cryopreservation process. The beneficial properties of quercetin on various parameters of fresh and post-thaw sperm in different species are clarified in this review. More in-depth investigations are required to clarify quercetin's mechanism of action in different animal species.

Impacts of polyphenols on laying hens' productivity and egg quality: A review.

There has been a rapid increase in the world's output of main poultry products (meat and eggs). This reflects customer desire for these high-quality and safe products and the comparatively low price. Recently, natural feed additives, plants and products have been increasingly popular in the poultry and livestock industries to maintain and improve their health and production. Polyphenols are a type of micronutrient that is plentiful in our diet. They are phytochemicals that have health benefits, notably cardiovascular, cognitive function, antioxidant, anti-mutagenic, anti-inflammatory, antistress, anti-tumour, anti-pathogen, detoxification, growth-promoting and immunomodulating activities. On the other hand, excessive polyphenol levels have an unclear and sometimes negative impact on gastrointestinal tract health, nutrient digestion, digestive enzyme activity, vitamin, mineral absorption, laying hens performance and egg quality. As a result, this review illuminated polyphenols' various sources, classifications, biological activities, potential usage restrictions and effects on poultry, layer productivity and egg external and internal quality.

Three-dimensional (3D) cell culture: a valuable step in advancing treatments for human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common malignant cancer and the third most frequent cause of tumour-related mortality worldwide. Currently, several surgical and medical therapeutic strategies are available for HCCs; however, the interaction between neoplastic cells and non-neoplastic stromal cells within the tumour microenvironment (TME) results in strong therapeutic resistance of HCCs to conventional treatment. Therefore, the development of novel treatments is urgently needed to improve the survival of patients with HCC. The first step in developing efficient chemotherapeutic drugs is the establishment of an appropriate system for studying complex tumour culture and microenvironment interactions. Three-dimensional (3D) culture model might be a crucial bridge between in vivo and in vitro due to its ability to mimic the naturally complicated in vivo TME compared to conventional two-dimensional (2D) cultures. In this review, we shed light on various established 3D culture models of HCC and their role in the investigation of tumour-TME interactions and HCC-related therapeutic resistance.

Silver-Silica nanoparticles induced dose-dependent modulation of histopathological, immunohistochemical, ultrastructural, proinflammatory, and immune status of broiler chickens.

Silver nanoparticles (AgNPs) are a powerful disinfectant, but little information is available on their potential use as a growth promoter and the safety margin of this. In this study, 480 1-day-old Cobb chicks were assigned to one control and three treated groups. The treated groups were supplemented with silver-doped silica nanoparticles (SiO2@AgNPs) at three dietary levels (8, 16, and 20 mg/kg diet) for 35 days. The results revealed no significant changes in the growth performance and oxidative parameters, and in most of the hematological and biochemical parameters among the control and treated groups. In contrast, dose-dependent adverse effects were exerted on the histopathological structure and immunohistochemical expression of CD45 in liver, kidneys, and lymphoid organs (spleen, bursa, and thymus). In addition, the relative weight of lymphoid organs and the serum levels of immunoglobulins M and G were significantly diminished. Moreover, the gene expression of proinflammatory cytokines (IL-ß1 and TNF-α) and the ultrastructural morphology in breast muscle showed significant dose-dependent alterations. It could be concluded that the dietary supplementation of SiO2@AgNPs at a level of 8 mg/kg diet or more has dose-dependent proinflammatory and immunosuppressive effects on broiler chickens.

Growth, immunity, relative gene expression, carcass traits and economic efficiency of two rabbit breeds fed prebiotic supplemented diets.

The current study designed to evaluate the effect of oligosaccharide supplemented diets on growth performance, histomorphometric changes, economic efficiency and genetic expression of some growth and immunity-relative genes. One hundred and twenty weaned male rabbits, six weeks of age of two breeds (NZW and APPRI) were randomly allocated into six equal groups; the first supplemented with 0.3% Mannan-oligosaccharide (MOS), the second supplemented with 0.05% Isomalto-oligosaccharide (IMO) and the third considered a control group. Each group contained ten equal replicates. The highest Final body weight and feed consumption were recorded in MOS and IMO groups compared with control. Fortified feed diet with IMO significantly increased duodenal villi area and length than MOS and control groups. At the same time, Spleen white bulb area and length were significantly higher in MOS and IMO than control. Supplementation of MOS and IMO significantly improved carcass traits, economic efficiency and induced certain modifications in some major key genes involved in the regulation of nutrients metabolism, immunity and growth in different tissues. In conclusion, dietary supplementation of MOS and IMO had a desirable positive impact on productive and economic efficiency in the rabbit.

Effect of environmental factors on growth performance of Nile tilapia (Oreochromis niloticus).

Aquaculture is the practice of developing aquatic animals and plants under artificial environmental conditions, either in a controlled or semi-controlled environment. Due to high animal protein demand, it is one of the world's growing food production industries. It plays a vital role in contributing to food security and lowering the unemployment rate of the world's growing population. This review article aims to scope sight on the environmental factors that affect the growth and economic production process of Nile tilapia. Many of these factors are listed and analyzed in this review, such as stocking densities; various feed frequencies and feeding rates; water quality; water temperature; dissolved oxygen concentration; water pH degree; ammonia (NH3), nitrite (NO2), and nitrate (NO3) concentration; feeding regimes; feed cost; and tank culturing system of Nile tilapia. These factors can significantly alter body weight, composition, survival, behavior, feed intake, feed conversion ratio, feeding efficiency, and the health and reproduction of Oreochromis niloticus. Furthermore, feeding, growth, disease risks, and survival rates are all affected by water quality parameters. In general, higher growth performance of O. niloticus in aquaculture can be obtained by keeping the optimum quantity of feed with proper feeding rate and frequency, maintaining a good proportion of stocking density, and regularly evaluating water quality. This review article highlights-in details-the impact of various environmental factors on growth performance criteria of Nile tilapia (Oreochromis niloticus).

Betaine and related compounds: Chemistry, metabolism and role in mitigating heat stress in poultry.

Betaine can operate as an osmolyte and a methyl donor. Betaine is an osmolyte and a methyl donor. Betaine is likewise a zwitterion with osmotic capabilities that can help an animal cope with osmotic stress. Previous investigations have suggested that betaine has various impacts, albeit these studies do not consistently provide the same results. Dietary betaine has received a lot of attention owing to its osmoprotectant, methionine-sparing and antioxidant properties. Betaine is extensively assessed concerning performance and body composition. The tolerance to high temperatures, flock livability, and breast meat output is among the factors frequently mentioned in the literature as being altered by betaine. Betaine, a multi-nutritional agent, may help poultry resist heat stress and poor management. A common subject of betaine research is the idea of betaine saving some methionine. Although research on betaine may not always come to the same results, some discoveries repeat themselves. Because of their effectiveness in increasing growth performance, feed utilization, meat quality, and alleviating heat stress in chicken farms, betaine and methionine are extensively used as feed supplements in poultry diets. This review highlights the influences of betaine on poultry performance, meat quality, carcass characteristics, antioxidant activity, in addition to its role in mitigating heat stress.

Heat stress in poultry with particular reference to the role of probiotics in its amelioration: An updated review.

Global climate change is accelerating at an unprecedented rate, and the consequences of global warming are expected to worsen. Many heat waves have recently hit various parts of the world, causing major losses in livestock, particularly in the poultry sector, resulting in massive mortalities and catastrophic economic losses. Therefore, the current review sheds light on the effects of heat stress on the poultry industry, and discusses the factors relevant to these harmful effects on behavior, bone development, blood chemistry and physiological changes, pathogenesis, and immune responses. Potential methods to ameliorate the heat stress response in birds, with particular reference to the role of probiotics in controlling such problems, is further discussed.

Influence of COVID-19 on the sustainability of livestock performance and welfare on a global scale.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently spreading worldwide. The pandemic has already had significant adverse effects on human civilization, the environment, and the ecosystem at national and global levels. Moreover, the various sectors of the food production chain, particularly agriculture and livestock, have also been significantly affected in terms of production sustainability and economic losses. The global pandemic has already resulted in a sharp drop in meat, milk, and egg production. Restrictions of movement at national and international levels, implemented as a part of control strategies by public health sectors, have negatively impacted business related to the supply of raw materials for livestock farmers and farm outputs, veterinary services, farmworkers, and animal welfare. This review highlights the significant impacts of COVID-19 on the sustainability of livestock performance, welfare on a global scale, and strategies for mitigating these adverse effects.

Beneficial effects of rumen-protected methionine on nitrogen-use efficiency, histological parameters, productivity and reproductive performance of ruminants.

Providing essential amounts of balanced nutrients is one of the most vital aspects of livestock production. Among nutrients, protein has an essential role in many physiological functions of animals. Amino acids in needs for both high and medium yielding ruminant animals are not fully covered by microbial degraded feed sources in the rumen of animals, and they must be met by protecting the proteins from being broken down in the rumen; hence, the dietary supplementation of rumen-protected proteins (RPP), including mainly rumen-protected methionine (RPM), became imperative. Many researchers are interested in studying the role of (RPM) in ruminant animals concerning its effect on milk yield, growth performance, digestibility, dry matter intake and nitrogen utilization efficiency. Unfortunately, results obtained from several investigations regarding RPM indicated great fluctuation between its useful and useless effects in ruminant nutrition particularly during early and late lactation period; therefore, this review article may be helpful for ruminant farm owners when they decide to supplement RPM in animal's diet. Conclusively, supplementation of RPM often has a balanced positive influence, without any reported negative impact on milk yield, growth performance and blood parameters especially in early lactating ruminant animals and when used with the low crude protein diet.

Pathological and Immunohistochemical Microscopy of Natural Cases of Canine and Feline Neoplastic Mammary Lesions.

Mammary cancer is the second most common tumor worldwide. Small animal mammary neoplasms provide an outstanding model to study cancer in humans, as tumors in both share a similar environment, histopathologic features, and biological behavior. This study aims to investigate the percentage and microscopy of breast tumors in affected dogs and cats; its relationship to breed, age, and sex; and the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), Ki-67, and cytokeratin 8. Twenty-four females (12 dogs and 12 cats) and one male were examined from February 2018 to February 2020. The highest percentage of mammary neoplasia from the highest to the lowest manifested as tubular carcinoma, leiomyosarcoma, fibroadenoma, and cystic papillary carcinoma. The current study reported the second micropapillary invasive carcinoma in a male cat and the third lipid-rich carcinoma in a female cat. Although tubular carcinoma was the most common mammary neoplasm in cats, leiomyosarcoma was the most common in dogs. The immunohistochemical staining revealed diffuse and intense cytoplasmic immunoreactivity for cytokeratin 8 in lipid-rich carcinomas. However, moderate expression of ER in benign tumors and slight to moderate ER expression in malignant mammary lesions were reported. On the contrary, there was a negative PR expression in benign lesion. It could be concluded that a close relationship between ER expression and nuclear antigen Ki-67 was found.

Aging-Related Functional and Structural Changes in Renal Tissues: Lesson from a Camel Model.

Renal aging is a progressive, physiological, and anatomical change that naturally occurs in all animal species. To date, no information is available concerning the aging-related structural and functional changes in camel kidneys. A total of 25 healthy male camels (14 aged 4­6 years and 11 aged 18­22 years) were included in this study. After the camels were slaughtered, samples were collected from all the camels' kidneys and prepared for histopathological, immunohistochemical, and gene expression evaluations. The most striking observation was the significant decline in the immunohistochemical abundance of podocin and the significant upregulation of smoothening in the aging camels' kidneys. However, the nonsignificant changes have reported for nephrin, calbindin, autophagy 5 (ATG5), aquaporin 1, and toll-like receptor 9. Furthermore, the mRNA expressions of sirtuin 1, superoxide dismutase 1, superoxide dismutase 2, peroxisome proliferator-activated receptor alpha, B-cell lymphoma 2 (Bcl-2), and erythropoietin were significantly decreased in the aging camels' kidneys. While the significant upregulation of Bcl-2-associated X protein and the nonsignificant increase in ATG5 expression levels were reported in the aging camels' kidneys. The present findings provide better understanding of the complex events and initiating factors of aging, allowing for the development of a future therapeutic strategy to preserve adequate renal function throughout life.

Expression of Acute Phase Protein, Glial Fibrillary Acidic Protein, Epithelial Cadherin, and S100 Protein in Brain Tissues from Natural Cases of Ovine Encephalitic Listeriosis.

Listeriosis is a disease that is induced by infection with the Gram-positive bacterium Listeria monocytogenes. Much is still unknown about the pathogenesis of encephalitic listeriosis. We aimed to identify the contribution of glial fibrillary acidic protein (GFAP), epithelial cadherin (E-cadherin), S100, and acute-phase proteins (APPs) in pathogenesis, clinical and preclinical diagnosis of natural cases of encephalitic listeriosis. Of 1,325 Ossimi sheep, 64 were suspected of having listeriosis from 2018 to 2020. Prospective cohort evaluation of clinical and postmortem findings was performed, in addition to bacterial isolation, the measurement of APPs in serum and cerebrospinal fluid (CSF), and the histopathological and immunohistochemical evaluation of GFAP, S100, and E-cadherin. Infected sheep showed nervous symptoms ranging from neck stretching to complete paralysis. APPs were significantly increased in the CSF of both clinically and preclinically diseased animals; however, serum APPs were only significantly increased in clinically diseased animals. Histopathological evaluation revealed microabscesses, meningoencephalitis, and perivascular cuffing of the brainstem of infected sheep. Immunohistochemical investigations revealed strong expression of GFAP and S100 in necrotic areas and negative expression of E-cadherin. The measurement of CSF APPs could be useful in the preclinical diagnosis of sheep listeriosis. GFAP and S100 proteins could be involved in the pathogenesis of listeriosis; however, E-cadherin does not appear to be involved.

Dietary origanum essential oil improved antioxidative status, immune-related genes, and resistance of common carp (Cyprinus carpio L.) to Aeromonas hydrophila infection.

The use of herbal essential oils in aquafeeds is an important approach to maintain the fish health status. The origanum essential oil (OEO), extracted from Origanum vulgare, was included at levels of 0, 5, 10, 15, and 20 g per kg diet to evaluate its beneficial effects on antioxidant, immunity status, and expression of immune-related genes of common carp, Cyprinus carpio L. After 8 weeks, dietary inclusion of OEO significantly increased the activities of hepatic superoxide dismutase and catalase (P < 0.05); meanwhile, levels of hepatic malonaldehyde significantly decreased (P < 0.05). The levels of serum lysozyme activity, phagocytic activity, and phagocytic index have been linearly and quadratically increased by dietary OEO in a dose-dependent regime showing their highest levels in 15-20 g OEO/kg diet. Moreover, dietary OEO significantly upregulated the relative expression of hepatic interleukin-1beta (IL-1ß) and interleukin-10 (IL-10) genes (P < 0.05). Dietary OEO maintained the normal histomorphological criteria and density of melanomacrophage centers of spleens, and hematopoietic tissues of the anterior kidneys in all fish groups with respect to the control. After challenge with pathogenic bacterium Aeromonas hydrophila, the 10-day cumulative mortality significantly decreased (P < 0.05); meanwhile, the relative percent of survival of common carp significantly increased by OEO administration (P < 0.05) in a dose-dependent manner. The obtained results reflect the beneficial roles of dietary OEO to boost the antioxidative status and the immune responses in common carp with an optimum level of 15 g/kg diet.

Cellular and functional adaptation to thermal stress in ovarian granulosa cells in mammals.

Climate change represents a significant environmental challenge to human welfare. One of many negative impacts may be on animal reproduction. Elevated ambient temperature unfavourably influences reproductive processes in mammals. High temperature can affect reproductive processes such as follicle development and may alter follicular fluid concentrations of amino acids, fatty acids, minerals, enzymes, antioxidants defence and growth factors. These impacts may lead to inferior oocyte competence and abnormal granulosa cell (GCs) function. Mammalian oocytes are enclosed by GCs that secret hormones and signalling molecules to promote oocyte competence. GCs are essential for proper follicular development, oocyte maturation, ovulation, and luteinization. Many environmental stressors, including thermal stress, affect GC function and alter oocyte development and growth. Several studies documented a link between elevated ambient temperature and increased generation of cellular reactive oxygen species (ROS). ROS can damage DNA, reduce cell proliferation, and induce apoptosis in GCs, thus altering oocyte development. Additionally, thermal stress induces upregulation of thermal shock proteins, such as HSP70 and HSP90. This review provides an update on the influence of thermal stress on GCs of mammals. Discussions include impacts to steroidogenesis (estradiol and progesterone), proliferation and cell cycle transition, apoptosis, oxidative stress (ROS), antioxidants related genes, heat shock proteins (HSPs) and endoplasmic reticulum responses.

The Toxicological Aspects of the Heat-Borne Toxicant 5-Hydroxymethylfurfural in Animals: A Review.

The incidence of adverse reactions in food is very low, however, some food products contain toxins formed naturally due to their handling, processing and storage conditions. 5-(Hydroxymethyl)-2-furfural (HMF) can be formed by hydrogenation of sugar substances in some of manufactured foodstuffs and honey under elevated temperatures and reduced pH conditions following Maillard reactions. In previous studies, it was found that HMF was responsible for harmful (mutagenic, genotoxic, cytotoxic and enzyme inhibitory) effects on human health. HMF occurs in a wide variety of food products like dried fruit, juice, caramel products, coffee, bakery, malt and vinegar. The formation of HMF is not only an indicator of food storage conditions and quality, but HMF could also be used as an indicator of the potential occurrence of contamination during heat-processing of some food products such as coffee, milk, honey and processed fruits. This review focuses on HMF formation and summarizes the adverse effects of HMF on human health.

Probiotics in poultry feed: A comprehensive review.

The use of antibiotics to maintain animal well-being, promote growth and improve efficiency has been practised for more than 50 years. However, as early as the 1950s, researchers identified concern on the development of resistant bacteria for the antibiotics streptomycin and tetracycline used in turkeys and broilers respectively. These findings laid the groundwork for agricultural officials to impose stricter regulatory parameters on the use of antibiotics in poultry feeds. Probiotics are live micro-organisms included in the diet of animals as feed additives or supplements. Commonly known as a direct-fed microbial, probiotics provide beneficial properties to the host, primarily through action in the gastrointestinal tract (GIT) of the animal. Supplementation of probiotics in the diet can improve animal health and performance, through contributions to gut health and nutrient use. For instance, supplementation of probiotics has been demonstrated to benefit farm animals in immune modulation, structural modulation and increased cytokine production, which positively affect the intestinal mucosal lining against pathogens. Bacillus subtilis has been a popular bacterium used within the industry and was shown to improve intestinal villus height. Increasing the villus height and structure of the crypts in the GIT allows for the improvement of nutrient digestion and absorption. Tight junctions maintain important defences against pathogenic bacteria and cellular homeostasis. Heat stress can be a major environmental challenge in the poultry industry. Heat stress causes the bird to fluctuate its internal core temperature beyond their comfort zone. To overcome such challenges, poultry will attempt to balance its heat production and dissipation through behavioural and physiological adaptation mechanisms.

The first identification of contagious caprine pleuropneumonia (CCPP) in sheep and goats in Egypt: molecular and pathological characterization.

Contagious caprine pleuropneumonia (CCPP) is one of the most fatal and contagious diseases of goats. To date, the occurrence of CCPP in Egypt has not been reported. During the period from 2017 to 2018, 200 goats and 400 sheep from Matrouh Governorate (Al Alamein and El Hammam cities) were suspected to have CCPP; animals were examined to confirm the presence of CCPP infection as well as the epidemiological status, clinical features, and molecular and histopathologic characteristics of lung tissues. Additionally, a treatment trial was performed to assess the efficacy of anti-mycoplasma therapy in the treatment of clinical cases of this disease. The occurrence of CCPP was 32.5% and 5% in goats and sheep, respectively, while case fatality was 30% and 8% in goats and sheep, respectively. The clinical forms of CCPP in both sheep and goats varied from per-acute to acute or chronic cases. Histopathological analysis of lung tissues from dead cases (either sheep or goats) revealed different stages of broncho- and pleuropneumonia ranging from per-acute to acute or chronic stages. Lung tissues showed severe congestion of interalveolar capillaries, flooding of alveoli and bronchi with a fibrinous exudate, a high degree of pleural thickening, and multifocal areas of necrosis that were sometimes sequestered in the fibrous capsule. Isolation of Mycoplasma capricolum subspecies capripneumoniae (Mccp) was confirmed in all dead cases by agar and broth culture methods and polymerase chain reaction. The treatment trial revealed that the marbofloxacin and spiramycin groups had a higher cure rate (70%) than the oxytetracycline group (40%) and a lower fatality rate (30%) than the oxytetracycline group (60%). Conclusively, infection with CCPP in goats and sheep is considered to be novel for Mccp in Egypt, where this species is considered to be the main pathogen in goats, not in sheep. Additionally, it could be concluded that treatment may be effective only if given early. Further comprehensive surveys are required to investigate the risk of CCPP in goats and sheep in all Egyptian governorates.

The adaptogenic anti-ageing potential of resveratrol against heat stress-mediated liver injury in aged rats: Role of HSP70 and NF-kB signalling.

Heat stress (HS) is a major international problem which has attracted a considerable attention due to its oxidative tissue effects and high morbidity and mortality rates, especially among elderly people. Discovering an effective antioxidant is pivotal for overcoming HS-induced injury. Therefore, the aim of this study was to estimate the hepatic protective effects of orally supplemented resveratrol (RES) against HS-mediated liver injury in young and old male Wistar albino rats. Compared to control rats, RES administered orally at a dose of 20 mg/kg BW for 21 successive days efficiently ameliorated HS-induced oxidative damage by significantly increasing (P ≤ 0.05) the level of reduced glutathione and glutathione peroxidase, and decreasing the levels of malondialdehyde and TNF-α in hepatic tissue of both young and aged rats. However, level of NF-κB was downregulated significantly in aged rats rather than young rats. Moreover, RES significantly decreased (P ≤ 0.05) the serum levels of aspartate transaminase and alkaline phosphatase in both ages of rats compared to their corresponding HS-stressed rats. Furthermore, RES upregulated the immunohistochemical expression of caspase 3 and heat shock protein 70 in young and aged rats, however it was more pronounced in young one. In addition, RES administration moderately normalized (P ≤ 0.0001) the harmful effects of HS on the hepatic architecture of both young and aged rats. In conclusion, this study reveals for the first time that RES exerts promising hepato-ameliorative effects against HS-induced oxidative stress in the young and aged rats via its antioxidant, anti-inflammatory, and anti-apoptotic effect, as well as via its inhibitory effect against the NF-κB signalling in a cellular system.