Engineered exosome as a biological nanoplatform for drug delivery of Rosmarinic acid to improve implantation in mice with induced endometritis.

Endometritis is an inflammatory and histopathologic disease in uterine tissues that interferes with the proper decidualization and implantation of the embryo. In this study, rosmarinic acid (RA) is used as an anti-inflammatory agent that encapsulates in exosomes and is used to attenuate lipopolysaccharide (LPS)-induced endometritis and improve implantation. For this purpose, exosomes were loaded with RA and then administrated into the animal groups, including RA, exosome, RA plus exosome (RA + Exo), and RA-loaded exosomes (RALExo) groups. The concentrations of RA or exosomes used in this study were 10 mg/kg, and the compounds were injected into the uterine horn 24 h following the induction of endometritis. Upon the presence of inflammation detected by the histopathological method, the most proper groups were mated with male mice. The effect of the treatment group on the implantation rate, progesterone levels, and gene expressions were assessed by Chicago Blue staining, enzyme-linked immunosorbent assay (ELISA), and Quantitative PCR (qPCR), respectively. Results showed RALExo10 and RA10 + Exo10 groups improved pathological alterations, enhanced progesterone levels, increased implantation rate, as well as heightened expression levels of Leukemia inhibitory factor (LIF) and Mucin-16 (MUC-16) genes. Besides, the expression levels of inflammatory cytokines, including Transforming growth factor-ß (TGF-ß), Interlukine-10 (IL-10), Interlukine-15 (IL-15), and Interlukine-18 (IL-18), were regulated. Our findings indicated that the expression of LIF, Muc-16 genes as well as IL-18, were significantly correlated with serum progesterone concentrations and the implantation rate in the treatment groups. The RALExo10 and RA10 + Exo10 groups showed ameliorated implantation rates in experimental groups.

Robust adhesive nanocomposite sponge composed of citric acid and nano clays modified cellulose for rapid hemostasis of lethal non-compressible hemorrhage.

Massive bleeding control plays the main role in saving people's lives in emergency situations. Herein, modified cellulose-based nanocomposite sponges by polydopamine (PDA) and laponite nano-clay was developed to sturdily deal with non-compressible lethal severe bleeding. PDA accomplishes supreme adhesion in the bleeding site (∼405 kPa) to form strong physical barrier and seal the position. Sponges super porous (∼70 % porosity) and super absorbent capacity (48 g blood absorbed per 1 g sponge) by concentrating the blood cells and platelets provides the requirements for primary hemostasis. Synergistically, the nanocomposite sponges' intelligent chemical structure induces hemostasis by activation of the XI, IX, X, II and FVII factors of intrinsic and extrinsic coagulation pathways. Excellent hemostatic performance of sponges in-vitro was assessed by RBC accumulation (∼100 %), blood clotting index (∼10 %), platelet aggregation/activation (∼93 %) and clotting time. The nanocomposite sponges depicted super performance in the fatal high-pressure non-compressible hemorrhage model by reducing of >2, 15 and 3 times in the bleeding amount at New Zealand rabbit's heart and liver, and rat's femoral artery bleeding models, respectively compared to commercial hemostatic agents (Pvalue˂0.001). The in-vivo host response results exhibited biosafety with no systemic and significant local inflammatory response by hematological, pathological and biochemical parameters assessments.

Enhanced anti-inflammatory effect of Rosmarinic acid by encapsulation and combination with the exosome in mice with LPS-induced endometritis through suppressing the TLR4-NLRP3 signaling pathway.

The TLR4-NLRP3 signaling pathway plays an essential role in the development of inflammation and especially endometritis. Rosmarinic acid (RA) can have potent anti-inflammatory effects in the drug-loading system. The purpose of this was to evaluate the anti-inflammatory effects of RA loaded to exosomes (RLE) on lipopolysaccharide (LPS)-induced endometritis in mice. RA was loaded into serum-derived exosome, using sonication methods. Animals in the treatment groups were subjected to uterine horn injection of RA, exosome, RA combination with exosome (R+E), and RA loaded to exosome (RLE) in uterine horn by two dosages in each group (5 and 10 mg/kg of RA or exosome), 24 h after inducing endometritis. Histopathological analysis, MPO production, immunohistochemistry, and qPCR were used to determine whether the treatment groups were adequate in controlling inflammation. The results showed that treatment groups, and mainly RLE10 and R10 +E10 groups, could modulate pathological changes, inhibit myeloperoxidase (MPO) activity, and significantly reduce the gene and protein expression of TLR4, NLRP3, inflammatory cytokines such as IL-1ß, IL-18, and TNF-α, and lastly, GSDM-D as a pyroptosis factor. In conclusion, RA loaded and combination with exosomes at a dosage of 10 mg/kg (RLE10 and R10 +E10) improved endometritis in mice through a suppressing TLR4-NLRP3 signaling pathway.

Efficacy of dietary live or heat-killed Bacillus subtilis in goldfish (Carassius auratus) infected with Ichthyophthirius multifiliis.

BACKGROUND: The beneficial effects of Bacillus subtilis on growth, immune response, and disease resistance against various diseases in different fish species have been proved. However, there are no data concerning this probiotic effect on skin mucosal immunity in fish infected with Ichthyophthirius multifiliis (Ich). Ich has a high mortality rate in both edible and ornamental fish and consequently is concerned with heavy economic losses. OBJECTIVES: Thus, we assessed the efficacy of live and heat-killed B. subtilis on skin immunity and histopathology in goldfish (Carassius auratus) infected with Ich. METHODS: Goldfish (144 fish, 2.38 g average weight) were stocked in nine glass tanks each in three replicates. Fish were fed 109 CFU g-1 live or heat-killed B. subtilis for 80 days. RESULTS: Probiotic administration in both viable and non-viable forms could enhance the growth performance in goldfish. Probiotic therapy also reduced the density of the parasite and histopathological level on skin and gill tissues of the treated fish. Real-time polymerase chain reaction analysis showed a higher expression of lysozyme and tumour necrosis factor-α in the treated groups compared to the control group. CONCLUSIONS: These data demonstrated the beneficial effect of B. subtilis as probiotic and paraprobiotic on growth performance and disease resistance to Ich infestation in goldfish.

Chronic Kombucha Beverage Consumption Attenuates Inflammatory Markers and Histopathology of Brain Tissue in Transnet Global Brain Ischemia in Rats.

There is evidence that kombucha beverage (KB), a traditional fermented beverage, has a preventive effect on experimental brain ischemia. According to our previous studies, pre-treatment of KB attenuates brain edema and improves motor skills and oxidative stress in a rat model of global brain ischemia. This study was designed to evaluate the effects of the pre-treatment of KB, as a novel agent, on pro-inflammatory parameters and brain histopathology changes following global brain ischemia. Adult male Wistar rats were randomly divided into the sham, the control, and the groups treated with kombucha (KB1 and KB2 groups). KB at doses 1 and 2 mL/kg was prescribed two-week consecutive days before induction of global brain ischemia. Global brain ischemia was induced by blocking common carotid arteries for 60 min and the following reperfusion by 24 h. The serum and brain levels of tumor necrosis factor-α(TNF-α), IL-1ß, histopathological change, and infarct volume are determined using the ELISA, hematoxylin and eosin (H&E), and 2,3,5-triphenyl tetrazolium chloride (TTC) staining, respectively. This study indicated that pre-treatment of KB significantly reduced infarct volume, the serum, and brain levels of TNF-α and IL-1ß. The histopathological finding of the brain tissue confirmed a protective role for pre-treatment KB in the ischemic rats. Thus, the present study showed that the beneficial effects of KB pre-treatment on brain ischemic may be mediated by decreasing pro-inflammatory parameters.

The Effect of miR-4800 Restoration on Proliferation and Migration of Human Breast Cancer Cells In Vitro.

Purpose: MicroRNAs (miRNAs) can contribute to cancer initiation, development, and progression. In this study, the effect of miRNA-4800 restoration on the growth and migration inhibition of human breast cancer (BC) cells was investigated. Methods: For this purpose, transfection of miR-4800 was performed into MDA-MB-231 BC cells using jetPEI. Subsequently, the expression levels of miR-4800 and CXCR4, ROCK1, CD44, and vimentin genes were measured using quantitative real-time polymerase chain reaction (q-RT-PCR) and specific primers. Also, the proliferation inhibition and apoptosis induction of cancer cells were evaluated by MTT and flow cytometry (Annexin V-PI method) techniques, respectively. Additionally, cancer cell migration after miR-4800 transfection was assessed by wound-healing (scratch) assay. Results: The restoration of miR-4800 in MDA-MB-231 cells resulted in the decreased expression level of CXCR4 (P ˂ 0.01), ROCK1 (P ˂ 0.0001), CD44 (P ˂ 0.0001), and vimentin (P ˂ 0.0001) genes. Also, MTT results showed restoration of miR-4800 could significantly reduce cell viability rate (P ˂ 0.0001) compared with the control group. Cell migration remarkably inhibited (P ˂ 0.001) upon miR-4800 transfection in treated BC cells. Flow cytometry data demonstrated that miR-4800 replacement considerably induced apoptosis in cancer cells (P ˂ 0.001) compared with control cells. Conclusion: Taken together, it seems that miR-4800 can act as a tumor suppressor miRNA in BC and play an essential role in modulating apoptosis, migration, and metastasis in BC. Therefore, it may be suggested as a potential therapeutic target in treating BC by performing additional tests in the future.

Dual targeting salinomycin-loaded smart nanomicelles for enhanced accumulation and therapeutic outcome in breast cancer.

Salinomycin is a polyether compound that exhibits strong anticancer activity and is known as the cancer stem cell inhibitor that reached clinical testing. The rapid elimination of nanoparticles from the bloodstream by the mononuclear phagocyte system (MPS), the liver, and the spleen, accompanied by protein corona (PC) formation, restricts in vivo delivery of nanoparticles in the tumor microenvironment (TME). The DNA aptamer (TA1) that successfully targets the overexpressed CD44 antigen on the surface of breast cancer cells suffers strongly from PC formation in vivo. Thus, cleverly designed targeted strategies that lead to the accumulation of nanoparticles in the tumor become a top priority in the drug delivery field. In this work, dual redox/pH-sensitive poly (ß-amino ester) copolymeric micelles modified with CSRLSLPGSSSKpalmSSS peptide and TA1 aptamer, as dual targeting ligands, were synthesized and fully characterized by physico-chemical methods. These biologically transformable stealth NPs were altered into the two ligand-capped (SRL-2 and TA1) NPs for synergistic targeting of the 4T1 breast cancer model after exposure to the TME. The PC formation was reduced sharply in Raw 264.7 cells by increasing the CSRLSLPGSSSKpalmSSS peptide concentration in modified micelles. Surprisingly, in vitro and in vivo biodistribution findings showed that dual targeted micelle accumulation in the TME of 4T1 breast cancer model was significantly higher than that of single modified formulation, along with deep penetration 24 h after intraperitoneal injection. Also, an in vivo treatment study showed remarkable tumor growth inhibition in 4T1 tumor-bearing Balb/c mice, compared to different formulations, with a 10% lower therapeutic dose (TD) of SAL that was confirmed by hematoxylin and eosin staining (H&E) and the TUNEL assay. Overall, in this study, we developed smart transformable NPs in which the body's own engineering systems alter their biological identity, which resulted in a reduction in therapeutic dosage along with a lowered off-target effect.

Extracorporeal Shock Wave Therapy as a Helpful Method for Rapid Osseointegration of Dental Implants: Animal Study.

The aim of this study was to assess the multi-phasic use of extracorporeal shock wave therapy (ESWT) as an adjuvant treatment to accelerate the osseointegration of titanium dental implants. Initially, twelve titanium mini-screws were inserted in femur bones of six New Zealand rabbits in three groups; the one-time treated group, the three-time treated group, and the control group (without ESWT). Then, 1800 focused shockwaves with an energy flux density of 0.3 mJ/mm2 in every phase were used. Fourteen days after the last phase of ESWT, the animals were sacrificed to assess the osseointegration of screws via micro-computed tomography scan (micro-CT scan), biomechanical pull-out test, and histopathological analysis. Pull-out and histopathology analysis showed that the ESWT significantly increased bone regeneration and osseointegration around the implants compared to the control group (p < 0.05). Moreover, the pull-out test confirmed that the three-time treated screws needed more force to pull the bone out compared to the other two groups (p < 0.05). The mean bone volume fraction between the control group, the one-time treated group, and the three-time treatment group were not statistically significant (p > 0.05) according to the micro-CT scan results. Based on our results, ESWT can be suggested as a non-invasive and cost-effective adjuvant for osseointegration of dental implants. However, more in vivo studies and clinical trials are needed for validation of this finding.

Natural infection with Toxoplasma gondii, Neospora caninum and Sarcocystis species in domestic pigeons (Columba livia domestica) in Iran.

Pigeons are common birds around the world and may act as intermediate hosts of the tissue cyst-forming apicomplexan parasites Toxoplasma gondii, Neospora caninum and Sacrocystis spp. This study aimed to provide an overview on the prevalence of and exposure to these parasites in Iranian domestic rock pigeon (Columba livia domestica) through molecular, serological and histopathological examination. Blood and tissue samples (i.e., brain, heart, gizzard, neck, thigh, and pectoral muscles) were taken from 100 pigeons. Sera were screened by agglutination tests for detection of anti- T. gondii and N. caninum antibodies, genomic DNA from tissue samples were assessed by respective species-specific PCRs, and histopathological examination of tissues was carried out. A seroprevalence of 45 % to anti-T. gondii and 35 % to anti-N. caninum IgG was recorded. PCR detected T. gondii DNA in 28 pigeons. Sacrocystis spp. was detected in one animal, but sequencing of the 28 S rRNA gene product did not reveal the identity of the species. Histopathology revealed myocarditis, myositis, and gliosis in the heart, skeletal muscles, and brain, respectively. No Sarcocystis tissue-cysts were detected, but T. gondii tissue cyst-like structures in the brain (i.e., 4 %) and heart (i.e., 3 %) were found by histology. Data reported herein demonstrate that pigeons from Iran are infected with tissue cyst-forming apicomplexans, particularly T. gondii. Since domestic pigeons are in close contact with human populations, and consumption of their meat and egg is popular in different societies, control strategies for minimizing the risk of infection in both pigeons and humans are suggested.

Suppression of the malignancy of mammary tumor in mice model by inactivated preparation of Mycobacterium obuense.

Breast cancer (BC) is a significant cause of global mortality in women. This study was aimed to evaluate the immune-activation of malignant BC via the administration of attenuated Mycobacterium obuense. For this purpose, an in vivo model was developed with BALB/c mice. Mice were injected with 2.00 × 106 4T1 cells with breast tumor cell line. Forty-two mice were equally divided into control as well as low dose (0.20 mg 100 µL-1) and high dose (0.50 mg 100 µL-1) groups of M. obuense to investigate gene expression in the antitumor effects of M. obuense. In one group, paclitaxel was administrated as a choice drug in BC treatment. Antitumor manners were characterized by cytotoxicity against tumor target cells, size of the tumor and the expression of some BC metastatic genes together with pathology. The MTT assay demonstrated that different concentrations of both low and a high dose of bacteria did present no cytotoxicity effect on 4T1 cells. According to our findings, M. obuense significantly repressed tumor growth. M. obuense downregulated the expression of collagen type I alpha 1 (COLIA1), cFos, alkaline phosphatase (ALP), claudin 3 (cldn3), and conversely, activated transcription factor 4 (ATF4) and Twist related protein-1 (Twist1). All these alternations induced a decrease in the migratory and invasive capabilities of BC. The result of pathology was indicative of tumor regression in the paclitaxel and HK- M. obuense -recipient group. Thus, it seems most likely that M. obuense might impinge upon cell growth and metastatic behavior of malignant cells exerting anti-tumor activity in BC.

Effects of sulfur dioxide, ozone, and ambient air pollution on lung histopathology, oxidative-stress biomarkers, and apoptosis-related gene expressions in rats.

PURPOSE OF THE STUDY: Ambient air pollution (AAP) has become an important health problem globally. Besides, several pieces of evidence indicate that air pollutants such as sulfur dioxide (SO2) and ozone (O3) are major contributors to a wide range of non-communicable diseases. The present study investigated the effects of AAP, sulfur dioxide, and ozone on oxidative stress, histopathology, and some apoptosis-related genes expressions of lung tissue in a rat model. MATERIALS AND METHODS: Thirty-two Wistar rats were randomly divided into the control, AAP, sulfur dioxide (10 ppm), and ozone (0.6 ppm) groups. After five consecutive weeks' exposure to the selected pollutants (3 h/day), lung tissues were harvested and immediately fixed with formalin. The samples were routinely processed, sectioned, stained with hematoxylin and eosin (H&E), and finally assessed for presence of pathological changes. Expression changes of BAX, p-53, EGFR, caspase-3, caspase-8 and caspase-9 were assayed using the RT-qPCR method. One hundred milligrams of lung tissues were extracted and the supernatants were used for assaying malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase activities. RESULTS: GPx activity was increased in the ozone (P = 0.05) and AAP (P < 0.001) groups and also MDA level in sulfur dioxide group (P = 0.008). Pathological lesions were mild, moderate, and severe in the sulfur dioxide, ozone, and AAP groups, respectively, as compared to control group (P ˂ 0.05). Exposure to AAP and sulfur dioxide enhanced BAX (P = 0.002) and caspase-8 (P < 0.001) mRNA expression, respectively. Caspases-3 and -8 mRNA expressions were elevated in ozone group (P < 0.001). CONCLUSIONS: The results indicated induction of oxidative stress. Our results suggest the apoptosis stimuli effect of AAP and also the extrinsic apoptotic pathway trigger effect of sulfur dioxide and ozone in the lung tissue in the concentrations used in the present study. The histopathological and the genes expression changes may be a result of the induced oxidative stress in the lung tissues.

Evaluation of a novel bioactive wound dressing: an in vitro and in vivo study.

OBJECTIVE: Hard-to-heal wounds, such as pressure ulcers and diabetic ulcers, are a major challenge for wound dressings. The aim of this study was to develop a bioactive dressing based on polymers and natural materials with unique biological and therapeutic properties. METHOD: The dressing was composed of an active layer containing polyvinyl alcohol (PVA), honey, curcumin and keratin, and an upper layer with lower hydrophilicity comprising PVA to induce flexibility. Physicochemical properties of the dressing were characterised by Fourier transform infrared spectroscopy, field emission scanning electron microscopy, swelling behaviour and antibacterial measurements. A wound healing study was performed using an experimental rat model and two different compositions of the bioactive dressing were compared with a commercial wound dressing (Comfeel, Coloplast, Denmark). Histopathological evaluation was conducted for this purpose. RESULTS: Characterisation results showed that a smooth bilayer film with two homogenous but distinct layers was produced. The dressing also provided adequate moisture to the wound environment without infection and adhesion due to dryness occurring. Our results exhibited significant bactericidal activity against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria and improved the wound healing process without any scarring. Histopathological findings demonstrated a significant higher healing rate in vivo together with well-formed epidermis, granulation tissue formation and tissue contraction, when compared with the commercial wound dressing. CONCLUSION: Our results demonstrated acceptable physical and healing effects for the novel bioactive wound dressing; however, more investigations are recommended.

The effects of heat-killed Tsukamurella inchonensis on intestinal morphology and humoral immune responses of broiler chickens.

BACKGROUND AND OBJECTIVES: Tsukamurella species are Gram-positive rods that exist in a broad range of environments. In this study, the efficacy of heat-killed Tsukamurella inchonensis on growth performance, intestinal morphology, and humoral immune responses of broiler chicken was evaluated. MATERIALS AND METHODS: Ross broiler chicks in the cage were randomly allocated to five groups. Trail diets were prepared by adding 106 cells per bird of heat-killed T. inchonensis into the basal trading diet for group 1 continuously dosed for 24 h from day 1 to day 13, and for group 2, 24 h on days 1 to 5; 8; 9, 12 and 13. Group 3 was received 106 bacteria as a subcutaneous injection on days 1, 6, and 12. Groups 4 and 5 were not received T. inchonensis during the experiment period. RESULTS: Feed intake (FI) and feed conversion ratio (FCR) were not altered by different delivery methods of T. inchonensis supplementation. The pulsed dosed in feed tended to provide higher body weight gain (BWG) than the negative control groups. T. inchonensis treatments, never less of the ways of delivery, boosted (P<0.05) the antibody titers to Newcastle disease virus (NDV), and avian influenza (AI) (H9N2) virus, especially when broiler chickens treated with pulse dosed in the feed. The most significant intestinal development (p<0.05) was observed between groups 1 and 2. There were no significant differences in the thymus, liver, and bursa of Fabricius relative weight. Still, there were significant increases in the relative weight of spleen on day 14 in vaccinated chickens treated with T. inchonensis pulse dosed. CONCLUSION: It seems that the supplementation of T. inchonensis in the broiler diet can improve intestinal morphology and humoral immune response, which was represented by increased antibody response to NDV, and AI vaccines significantly, but it cannot affect FI and FCR.

The Beneficial Effects of Actinomycetales Immune Modulators in the Pancreas of Diabetic Rats.

Purpose: Type 1 diabetes mellitus (T1DM) has dramatically increased in recent years, especially in young people, and limits the life quality of the patients involved. Thus, many researchers are performing extensive studies to find alternative treatments for DM. Methods: Here, we evaluated the improvement effects of the heat-killed Actinomycetales species, including Gordonia bronchialis, and Tsukamurella inchonensis in streptozotocin (STZ)- diabetic rats by biochemical, immunological, and histopathological examinations. Results: The present findings exhibited a dramatic and progressive alteration in the serum levels of interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) in the diabetic group, which were related to the blood glucose and insulin levels, oxidative stress defense (evaluated by TAC and MDA activities), and the pancreas biochemical indicators (such as amylase and lipase). More importantly, the present results were consistent with the histopathological findings, which included cellular degeneration, vascular congestion, hemorrhage, focal necrosis associated with mononuclear cell infiltration. Interestingly, all of the diabetic changes in the blood serum and tissues improved remarkably in the treated groups by Actinomycetales species. Conclusion: Surprisingly, most of the current diabetic complications effectively attenuated after oral administration of both Actinomycetales species, particularly with a high dose of T. inchonensis. Thus, it is concluded that the heat-killed Actinomycetales species can prevent and improve the progression of T1DM and its various complications profoundly.

Effect of sulfur dioxide exposure on histopathology and morphometry of pancreatic islet cells and glycemic indices in Wistar rats.

Sulfur dioxide (SO2) is a ubiquitous air pollutant. Recent studies suggest that SO2 is a momentous risk factor for diabetes mellitus (DM). The present investigation aimed to evaluate the effects of SO2 exposure on histopathology and morphometry of pancreatic islet cells and serum glycemic indices in rats. Sixteen male Wistar rats were divided equally into SO2 and control groups. SO2 group was exposed to 10 parts per million (ppm) SO2 for 5 weeks (6 days a week, 3 h/day) and control group to filtered air for the same time as SO2 group. Blood serums were collected and pancreatic tissue isolated. Glycemic indices were measured. Pathological and morphometric changes were studied in the pancreatic tissues. Exposure to SO2 caused a significant increase in blood glucose but did not significantly change insulin and HbA1c serum levels and HOMA-IR. There were significant differences in vascular congestion (p= 0.02) and insulitis (p= 0.04) between the groups. SO2 inhalation significantly reduced beta cell number and beta-alpha cell ratio compared with the control group (p=0.03 and p<0.0001, respectively). These findings suggest that SO2 exposure damages pancreatic tissue which subsequently influences either the incidence of DM or the trend of diabetic complications.

Vaccination with rEGVac elicits immunoprotection against different stages of Echinococcus granulosus life cycle: A pilot study.

Vaccination against dog-sheep transmission cycle is necessary to control cystic echinococcosis (CE) infection. A multi-epitope multi-antigenic recombinant vaccine was developed-comprising the three putative vaccine antigens EG95, Eg14-3-3 and EgEnolase-was cloned and expressed. In a pilot experiment, the multi-antigen vaccine was assessed in 15 dogs and 15 sheep (five experimental groups and three animals in each group) by two subcutaneous doses 28 days apart. To evaluate the efficacy of the vaccine candidate first immunological analysis were done comprising IgG and IgE antibodies and the cytokine IL-4 in sera of the immunized dogs and sheep. Serum IgG, IgE, and IL-4, in particular in the dogs, were increased after the two rounds of vaccine candidate injection, while the total number of hydatid cysts was reduced (~85.43%). This pilot trial indicated significant immune protection efficacy against E. granulosus especially in dogs, while its efficacy in sheep was not as high as dogs. The multi-antigenic candidate vaccine is proposed as a protective vaccine modality in both dogs and sheep.

Hepatic Capillaria hepatica (Bancroft, 1893) infection in cat (Felis catus)-histopathological findings and first report from Iran.

Capillaria hepatica (syn. Calodium hepaticum) is a globally distributed nematode with a high affinity to the liver of a wide range of mammalian hosts, including humans. Documented reports of the nematode in cats and associated histopathology are rare. Here, we describe a case of C. hepatica infection in a 5-year-old male stray cat from Iran. At post-car accident necropsy, all body parts appeared normal except for the liver, in which a few yellowish-white granulomatous nodules were observed through the capsule and in the organ. Histopathological examination of the tissue revealed a large number of clustered parasite eggs in the parenchyma. The barrel-shaped, un-embryonated eggs (55.19 × 28.37 µm), with inconspicuous caps at both ends, were covered with striated shells. The presence of ova in the liver tissue had resulted in the development of hepatic inflammation with hepatocellular necrosis associated with the development of multifocal granulomas. As predators of small rodents, the cats might have a significant role in the epidemiology of C. hepatica. Infection of hosts through ingestion of embryonated eggs in contaminated water, food, or soil is of major importance in the epidemiology of C. hepatica. Since the rare reports of feline infection have come mainly from accidental detection of the parasite, any hepatic disease presenting difficulties to find an etiological agent may virtually be associated with the infection with this little-known nematode.

Restoring of miR-193a-5p Sensitizes Breast Cancer Cells to Paclitaxel through P53 Pathway.

Purpose: Recent evidence presented the important role of microRNAs in health and disease particularly in human cancers. Among those, miR-193 family contributes as a tumor suppressor in different benign and malignant cancers like breast cancer (BC) via interaction with specific targets. On the other hand, it was stated that miR-193 is able to modulate some targets in chemoresistant cancer cells. Therefore, the aim of this study was to evaluate the potential function of miR-193a-5p and paclitaxel in the apoptosis induction by targeting P53 in BC cells. Methods: At first, miR-193a-5p mimics were transfected to MDA-MB-231 BC cell line which indicated the lower expression level of miR-193a-5p. Subsequently, the transfected cells were treated with paclitaxel. Then, cell viability, apoptosis, and migration were evaluated by MTT, flow cytometry and DAPI staining, and scratch-wound motility assays, respectively. Moreover, the expression levels of P53 was evaluated by qRT-PCR. Results: The expression level of miR-193a-5p was restored in MDA-MB-231 cells which profoundly inhibited the proliferation (P<0.0001), induced apoptosis (P <0.0001) and harnessed migration (P <0.0001) in the BC cells and more effectiveness was observed in combination with paclitaxel. Interestingly, increased miR-193a-5p expression led to a reduction in P53 mRNA, offering that it can be a potential target of miR-193a. Conclusion: Taken together, it is concluded that the combination of miR-193a-5p restoration and paclitaxel could be potentially considered as an effective therapeutic strategy to get over chemoresistance during paclitaxel chemotherapy.

Effects of Cornus mas Fruit Hydro-Methanolic Extract on Liver Antioxidants and Histopathologic Changes Induced by Cisplatin in Rats.

Cornelian cherry (Cornus mas) is a valuable source of phenolic antioxidants. The present study was aimed to investigate whether Cornus mas fruit hydro-methanolic extract (CMFE) can modulate the cisplatin-induced changes in liver antioxidant enzymes and histological structure. Forty Wistar rats were divided into a control group, cisplatin (Cis) group, CMFE group, CMFE 300 + Cis group, and the CMFE 700 + Cis group. After the intervention, blood and tissue samples were taken for biochemical and histopathological analysis. Cis caused reduction in the activity of liver antioxidant enzymes including SOD, GPx, TAC, and CAT and increased that of MDA. Moreover, exposure to Cis caused a reduction in serum level of AST, ALT, and ALP and a rise in serum level of GGT. Oral administration of CMFE for 16 days in the two different dosages at 300 and 700 mg/kg improved the Cis-induced changes of liver enzymes activity and serum enzymes level. Evaluating the histological structure of liver tissue, it was found that treatment by CMFE could ameliorate the Cis-induced changes to near normal histology. The results showed antioxidant and phenol contents in Cornus mas fruit could improve Cis-induced oxidative stress and liver histologic changes in rats.