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Cancer immunotherapies have been widely hailed as a breakthrough for cancer treatment in the last decade, epitomized by the unprecedented results observed with checkpoint blockade. Even so, only a minority of patients currently achieve durable remissions. In general, responsive patients appear to have either a high number of tumor neoantigens, a preexisting immune cell infiltrate in the tumor microenvironment, or an 'immune-active' transcriptional profile, determined in part by the presence of a type I interferon gene signature. These observations suggest that the therapeutic efficacy of immunotherapy can be enhanced through strategies that release tumor neoantigens and/or produce a pro-inflammatory tumor microenvironment. In principle, exogenous tumor-targeting bacteria offer a unique solution for improving responsiveness to immunotherapy. This review discusses how tumor-selective bacterial infection can modulate the immunological microenvironment of the tumor and the potential for combination with cancer immunotherapy strategies to further increase therapeutic efficacy. In addition, we provide a perspective on the clinical translation of replicating bacterial therapies, with a focus on the challenges that must be resolved to ensure a successful outcome. [ABSTRACT FROM AUTHOR]

Shrimp farming is a significant contributor to the GDP of several growing Asian countries. However, the emergence of Enterocytozoon hepatopanaei (EHP) infection has had a negative impact on the Indian shrimp market, leading to increased mortality and growth retardation among shrimp populations. In order to address this issue, a study was conducted to investigate the potential therapeutic effects of neem aqueous extract (NAE) in treating EHP infection in shrimp. This study employed various approaches, including toxicity testing in zebrafish larvae to determine safe and suitable doses of NAE, as well as long-term exposure trials on adult shrimp. The results of the study indicated that NAE exposure improved the antioxidant defence system by boosting SOD, CAT and NO levels and immunological response of infected shrimp, effectively reducing oxidative stress and enhancing the activity of prophenoloxidase (PPO). Furthermore, histological evaluations demonstrated a decrease in EHP spore development in the shrimp hepatopancreas, while staining analyses revealed the presence of spores in shrimp faeces. Furthermore, the potential bioactive compounds in the extract were observed using GC-MS analysis. These findings highlight the potential of NAE as a natural and effective treatment option for EHP infection in shrimp, which holds significant implications for the aquaculture sector. [ABSTRACT FROM AUTHOR]

From ancient times, humans have used mushrooms in different forms. Mushrooms have found their way into multiple cuisines, medicines, and other vital aspects of our lives. We have discovered and worked on different species of mushrooms. Some species of Clitocybe have not found their way into the research as they are poisonous. Many species of Clitocybe have not been studied for their therapeutically critical bioactive compounds. In this review, we have focused on the benefits of the compounds extracted from different species of Clitocybe. The compounds present in Clitocybe have been confirmed to have a wide range of beneficial effects, including antitumor, bacteriostatic, antifungal, antiviral, anti-inflammatory, antioxidant, antiaging, antidiabetic, hypoglycemic, immune stimulant, antiproliferative, neuroprotective, cardioprotective and chemopreventive properties. It has also found its way into the food industry with notable characteristics such as milk-coagulant, flavorings agent, organic food preservative, and yeast culture. There are studies confirming the use of compounds extracted from different species of Clitocybe as biological pest control. [ABSTRACT FROM AUTHOR]

Simple Summary: Custard apple (Annona squamosa) leaf extract (ASLE) is a phenolic-rich substance and considered a non-conventional feed additive. The present study aimed to evaluate the effect of ASLE dietary supplementation in the diet of Nile tilapia on growth performance, physiological status, and stress resistance. The results revealed that dietary ASLE, up to a 20 g/kg diet, improved growth and feed utilization. ASLE improved the hematological parameters, vital organ functions, and redox status in the fish. Furthermore, increasing ASLE dietary levels improved fish resistance against Aeromonas sobria challenge. Therefore, ASLE could be a potential feed additive in Nile tilapia diets. Plant extracts are a phytochemically-rich alternative to antibiotic and synthetic feed additives, with high systemic bioactivity in animals. The present study aimed to evaluate the effect of a hydroalcoholic extract of custard apple (Annona squamosa) leaf (ASLE) on the growth, hematobiochemical parameters, digestive enzyme activities, redox status, nonspecific immune response, and cold and bacterial infection tolerance in Nile tilapia (Oreochromis niloticus). A total of 300 Nile tilapia fingerlings (11.87 ± 0.48 g) were fed ASLE-supplemented diets at increasing levels of 0, 5, 10, 15, and 20 g/kg for 60 days. At the end of the feeding period, the fish were experimentally challenged with cold water stress or Aeromonas sobria, and mortalities were recorded for 10 days. The results revealed that the growth performance and feed conversion ratio were significantly improved with an increasing level of ASLE supplementation. The hematologic profile and hepato-renal functions were retained within a healthy range in the various groups supplemented with an ASLE diet. Antioxidant status was significantly improved in the serum of fish fed ASLE-supplemented diets, in terms of superoxide dismutase (SOD), catalase (CAT) activities, reduced glutathione, and total antioxidant capacity. Meanwhile, the myeloperoxidase (MPO) and malondialdehyde (MDA) levels decreased significantly. Similarly, there was a noticeable improvement in the hepatic CAT and SOD activities and a reduction of hepatic MDA. Marked improvements in lysozyme activity, nitric oxide production, complement3 level, and phagocytic activity were recorded in groups fed ASLE-supplemented diets, which peaked with the 20 g ASLE/kg diet. Moreover, the serum glucose and cortisol levels significantly declined in groups fed ASLE at levels of 15–20 g/kg compared to the other groups. Supplementation with ASLE increased the activities of protease, lipase, and α-amylase. ASLE supplementation at a concentration of 10–20 g/kg diet enhanced the resistance of Nile tilapia to A. sobria infection. According to this study, ASLE supplementation enhanced the antioxidant balance, non-specific immune response, physiological status, resistance against infection, and growth performance of Nile tilapia at supplementation levels of 10–20 g/kg diet. [ABSTRACT FROM AUTHOR]

Our study was performed to explore salmonella infection in Japanese quails, also its incidence, clinical signs, postmortem lesion, serotypes, antibiotic resistance, and virulence with an experimental treatment trial. A total of 100 samples were collected from quails suffering from diarrhea and mortalities from 10 farms (10 birds from each) at Kafr ElSheikh Governorate, Egypt. Samples were aseptically collected and were processed for the isolation and identification of salmonella spp. Incidence of salmonella infections was (17%), detected serotypes were S. infantis 58.8 % (10/17), S. salame17.6% (3/17), S. Kentucky 11.8 % (2/17), S. Isangi 5.8% (1/17), S. Colorado 5.8% (1/17). Virulence genes such as invA and sopB were detected in all examined isolates while no one had pefA and for antibiotics resistance genes all 10 isolates carried tetB, 3 isolates, and 2 isolates of them carrying qnrS and blaMox respectively. Susceptibility of isolated Salmonella serotypes to antimicrobial agents showed 100% resistance to oxytetracycline and erythromycin and serotypes were sensitive to fosfomycin (16/17) (94.11%). In the experimental design, 120 birds, 1day-old Salmonella free quail chicks, were used to study the pathogenicity of Salmonella isolates (S. Infantis). Quails Chicks were divided into 6 groups (20 per group), the first group (G1) was kept as non-infected control and group 2 (G2) as infected control, group 3 (G3) was non-infected and given organium oil from1-19 days, group 4 (G4) was infected and treated with fosfomycin on the 2nd-day postinfection for 5 days, group 5 (G5) was infected and given organium oil from 1-19 day and, group 6 (G6) was infected and treated with fosfomycin on the 2nd-day post-infection for 5 days and given organium oil from 1-19 day. The birds in groups (2, 4, 5, and 6) were infected orally with 0.5 ml of S. Infantis containing 107CFU on the 10th-day of age. Observation of the chicks daily for clinical signs and mortalities was done for 2 weeks post-infection. PM examination of dead and very sick chicks and bacteriological reisolation. Our results showed that the birds that received fosfomycin and organium oil together (G6) showed more favorable clinical signs, mortality rate, post-mortem lesions, recovery rate, and shedding rate then (G4), and (G5), respectively than (G2). In the experimental design, blood samples were collected at 12 and 19 days of age (5 birds from each group each time) for Serum analysis, and total and differential leukocytes count, the analysis of variance showed that positive significant effect on treated groups (G3, G5, G6) with organium oil on total protein, albumin, globulin, and albumin globulin ratio (P<0.01), and on Total leucocytes count, basophils%, eosinophil %, heterophils %, lymphocytes%, and monocytes% (P<0.01) in comparison with non-treated groups (G1, G2, G4) with organium oil. So, we recommend the use of organium oil as an immune supplement in healthy birds, and in combination with the effective antibiotic for the treatment of diseased broiler Japanese quail with salmonellosis. [ABSTRACT FROM AUTHOR]

Nowadays, many challenges are facing by the fish farmer like infections (viral, bacterial and fungal) and environmental stress. Different drugs have been used against several infections, but sometimes they produce toxic effect in fish body and deteriorate the water quality, which in turn decrease the output of the aquaculture. To overcome these issues, herbal products are used in aquaculture and these are the perfect immune stimulator, antibiotic alternative and growth promotor. The current research was conducted to assess the effect of variant level of. Agaricus bisporus on immunity and haematological parameters of Oreochromis niloticus. A total of 120 healthy fishes with average weight 24.0 ± 12.5g were distributed randomly into four fiber glass tanks in triplicates (each tank contains 10 fishes). The experimental diet was prepared with variant concentration of mushroom such as 0% (control group) and 2%, 4% and 6% of extractions for the other three groups. Duration of the experimental work was six weeks. Water quality parameters including temperature was 29 ± 0.5, DO: 5.7 ± 0.04 and pH: 7.5. Results revealed that the 6% Agaricus bisporus has shown higher lysozyme activity and ACH50 level, while no significant enhancement was observed in Ig. Beside this all the haematological parameters including WBC, RBC, Hb, Het and differential leucocyte was observed higher in all the groups as compared to control group. It was concluded that 6%Agaricus bisporus can be use as immune-stimulant, and can help the farmers to overcome the emerging aquaculture problems. [ABSTRACT FROM AUTHOR]

Plant extracts are a phytochemically-rich alternative to antibiotic and synthetic feed additives, with high systemic bioactivity in animals. The present study aimed to evaluate the effect of a hydroalcoholic extract of custard apple (Annona squamosa) leaf (ASLE) on the growth, hematobiochemical parameters, digestive enzyme activities, redox status, nonspecific immune response, and cold and bacterial infection tolerance in Nile tilapia (Oreochromis niloticus). A total of 300 Nile tilapia fingerlings (11.87 ± 0.48 g) were fed ASLE-supplemented diets at increasing levels of 0, 5, 10, 15, and 20 g/kg for 60 days. At the end of the feeding period, the fish were experimentally challenged with cold water stress or Aeromonas sobria, and mortalities were recorded for 10 days. The results revealed that the growth performance and feed conversion ratio were significantly improved with an increasing level of ASLE supplementation. The hematologic profile and hepato-renal functions were retained within a healthy range in the various groups supplemented with an ASLE diet. Antioxidant status was significantly improved in the serum of fish fed ASLE-supplemented diets, in terms of superoxide dismutase (SOD), catalase (CAT) activities, reduced glutathione, and total antioxidant capacity. Meanwhile, the myeloperoxidase (MPO) and malondialdehyde (MDA) levels decreased significantly. Similarly, there was a noticeable improvement in the hepatic CAT and SOD activities and a reduction of hepatic MDA. Marked improvements in lysozyme activity, nitric oxide production, complement3 level, and phagocytic activity were recorded in groups fed ASLE-supplemented diets, which peaked with the 20 g ASLE/kg diet. Moreover, the serum glucose and cortisol levels significantly declined in groups fed ASLE at levels of 15–20 g/kg compared to the other groups. Supplementation with ASLE increased the activities of protease, lipase, and α-amylase. ASLE supplementation at a concentration of 10–20 g/kg diet enhanced the resistance of Nile tilapia to A. sobria infection. According to this study, ASLE supplementation enhanced the antioxidant balance, non-specific immune response, physiological status, resistance against infection, and growth performance of Nile tilapia at supplementation levels of 10–20 g/kg diet.

Our objective was to evaluate the effects of a non-specific immune stimulant (IS) administered around transportation on health scores (HS), average daily gain (ADG), disease treatment and mortality of Jersey and Jersey-cross calves during the rearing period. Newborn calves (4 d ± 1) were randomly allocated to receive either 1 mL of saline (CON; n = 438), 1 mL of IS before transport (BTIS; n = 431), or 1 mL of IS immediately after transport (ATIS; n = 436). Calves were health scored weekly for 3 weeks after transport. The data were analyzed using multivariable linear mixed models and multivariable logistic regression models. Kaplan-Meier survival analysis was performed for time to event analysis. Treatment, birth weight, breed, site of birth, serum total solids, dam parity, season of enrollment, and metaphylaxis were offered to models. Differences in respiratory and fecal HS, and ADG between treatment groups were not statistically significant. A total of 196 (15.0%) calves were treated at least once for any disease and 52 calves were treated multiple times. The proportion of calves treated for respiratory disease and/or diarrhea were 14.4, 14.4, and 16.2% for BTIS, ATIS and CON groups, respectively. Although the differences in the likelihood of treatment for both respiratory disease and/or diarrhea during the first 9 weeks of life was not statistically different between groups, we observed that more calves in the control group received disease treatments around 15 days of age compared with calves that received IS. The likelihood of treatment for respiratory diseases alone during the first 30 days of life was smaller in the calves that received IS before transportation when compared to the control group. Only 18 (1.4%) calves died within the study period. The calf mortality likelihood was not statistically different between study groups; however, fewer calves in the IS groups died when compared to CON. In conclusion, the use of IS around transportation did not influence weekly HS, ADG, and the number of disease treatments during the rearing period, but administering IS before transportation resulted in fewer treatments of respiratory diseases during the first 30 days post-transport and marginally lower mortality rates during the rearing period.

Calreticulin (CRT) is a multifunctional ubiquitous protein that is widely presented in all cells in eukaryotes except erythrocytes. CRT is well known for diverse cellular functions such as endoplasmic reticulum (ER)-specialized protein quality control during protein synthesis and folding, in-vivo Ca2+ homeostasis, antigen presentation, phagocytosis, wound-healing, proliferation, adhesion, and migration of cells. In the current study, we identified CRT from Hippocampus abdominalis (HaCRT) and analyzed expression profiles and functional properties. The cDNA sequence of HaCRT was identified with an open reading frame of 1226 bp. The molecular weight of HaCRT was estimated as 49 kDa. The in-silico study revealed conserved sequence arrangements such as two CRT signature motifs (5′-KHEQSIDCGGGYVKVF-3′ and 5′-LMFGPDICG-3′), triplicate repeats (5′-IKDPEAKKPEDWD-3′, 5′-IPDPDDTKPEDWD-3′, 5′-IPDPDAKKPDDWD-3′), signal peptide and an ER-targeting 5′-KDEL-3′ sequence of HaCRT. Close sequence similarity of HaCRT was observed with Hippocampus comes from phylogenetic analysis and pairwise sequence comparison. From quantitative polymerase chain reaction (qPCR) results, HaCRT was ubiquitously distributed in all tested tissues and expression levels of HaCRT were significantly modulated in blood, liver and gill tissues after stimulation with Streptococcus iniae , Edwardsiella tarda , polyinosinic:polycytidylic acid, and lipopolysaccharides. Bacterial- and pathogen-associated molecular patterns-binding activities were observed with recombinant HaCRT (rHaCRT). The treatment of murine macrophages with rHaCRT induced the expression of immune genes, such as tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS), and interleukin-1β (IL-1β). Furthermore, rHaCRT exhibited wound-healing ability. Based on the results from the above study, we suggest that HaCRT play an indispensable role in the immunity of big-belly seahorses by recognition and elimination of pathogens as well as the tissue repairing process. • Calreticulin was identified and characterized from Big-belly seahorse (HaCRT). • Bacterial- and PAMPs-binding activity of recombinant HaCRT (rHaCRT) was identified in-vitro. • The rHaCRT was able to activate macrophages by inducing the production of cytokines and interleukins. • The rHaCRT demonstrated the detectable wound-healing ability. • HaCRT was ubiquitously expressed in all tested tissues and the expression was modulated upon immune challenge. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increasing population and food provision is one of the most important problems in the world, thus aquaculture plays an important role in the production of food and human needs. OBJECTIVES: This study was to investigate the effect of Celmanax prebiotic on growth performance, hematological and biochemical factors of juvenile Oncorhynchus mykiss. METHODS: For this study, 780 juvenile rainbow trout with an average weight of 18 ± 2 g were randomly divided into four groups with three replications. 0, 2, 4 and 6 percent of Celmanax were added into diets and the fishes were fed with 5% of body weight for 8 weeks 3 times. At the end of experiment, investigation of the growth indices, blood sampling and serum preparation for hematological and biochemical tests were performed. RESULTS: The results showed that fishes fed with diets containing 4% Celmanax prebiotic had better growth indices (final length, final weight, weight gain, percentage of weight gain and specific growth rate) compared to control (P≤0.05). Comparison between experimental treatments demonstrated that immune indices significantly increased with increase of prebiotic levels in the diet (P≤0.05). So that, the highest level of hemoglobin, red blood cell, white blood cell and neutrophil were related to fishes fed with 6% of Celmanax prebiotic diet. Also, the highest levels of immunoglobulin, albumin, glucose and lsozyme and the lowest levels of cholesterol and triglyceride and cholesterol were observed in fishes fed with 6% of Celmanax prebiotic diet, which showed a significant difference with control (P≤0.05). CONCLUSIONS: Increasing levels of Celmanax prebiotic in the diet caused an improvement in the growth and immunity system of rainbow trout. [ABSTRACT FROM AUTHOR]

Ablation therapies have emerged as an effective tool for destroying cancerous tissue, but for advanced and disseminated tumors their application remains mainly a palliative measure. However, it is becoming increasingly clear that this limitation can be redressed by the use of intratumoral immune stimulating agents for amplifying potential antitumor immune responses that are induced by ablation therapies. A novel immune stimulating drug IP-001, a specific variant of the N-dihydrogalactochitosan (GC) family of molecules, has shown to be effective against metastatic tumors, when combined with different forms tumor ablation. It acts as a multi-function immune stimulant both by directly inhibiting cell membrane repair and recycling of ablation-damaged tumor cells, and indirectly by sequestering ablation-released tumor antigens, as well as recruiting and stimulating antigen presenting cells to induce a potent Th1 type T cell response against the cancer. In this review, we briefly discuss the current applications of local ablation for cancer treatment and the effects of GC in combination with other ablation therapies, a therapeutic approach that is pioneering the field of Interventional Immuno-Oncology (IIO).

Immune adjuvants have roles in immune activation for cancer therapy, and adjuvants derived from microbes have been applied. In this study, we propose the use of bioengineered vacuoles, derived from recombinant yeast with acute myeloid leukemia (AML) specificity and having a TLR-2-binding peptide (Vac T2BP ) on their surface, to induce a proinflammatory response as a dual-function nanomaterial for daunorubicin (DNR) delivery. Our results demonstrate that nanosized, isolated Vac T2BP induced HL-60 cell-specific DNR delivery and apoptosis. Furthermore, we observed the selective release of high-mobility group box 1 from apoptotic HL-60 cells by DNR@Vac T2BP . We concluded that DNR@Vac T2BP exhibited target selectivity, and the indiscriminate occurrence of damage-associated molecular patterns (DAMPs) was inhibited by the Vac T2BP carrier. The therapeutic efficacy of DNR@Vac T2BP was confirmed in AML xenograft mice, with about 82% tumor growth inhibition. Following drug delivery, apoptotic cells and DAMPs with residual Vac T2BP (apop DNR@VacT2BP ) upregulated the proinflammatory immune response of macrophages. In addition, apop DNR@VacT2BP enhanced phagocytosis activity. Macrophages stimulated by apop DNR@VacT2BP suppressed cancer proliferation by about 40%. In summary, our results suggest that dual-functional vacuoles with a target-specific peptide can be a potential strategy for selective drug delivery and construction of an immune environment to fight cancer, thereby improving prognosis.

Holstein cows (n = 30) were balanced by days in milk, milk production, and parity (91 ± 5.9 d in milk, 36.2 ± 2.5 kg/d, and 3.1 ± 1.4, respectively) and fed OmniGen-AF (OG; Phibro Animal Health, Teaneck, NJ), an immune stimulant, at 0 g/cow per d for control (CON) or 56 g/cow per d for OG for 52 d on a commercial dairy. At 52 d of the study cows were randomly selected (n = 12) from both groups (6 OG and 6 CON) and housed in environmentally controlled rooms at the Agricultural Research Complex for 21 d at the University of Arizona. Cows were subjected to 7 d of thermoneutral (TN) conditions, 10 d of heat stress (HS), and 4 d of recovery (REC) under TN conditions. Feed intake, milk production, and milk composition were measured daily. Rectal temperatures (RT) and respiration rates (RR) were recorded 3 times per day (600, 1400, and 1800 h). Blood samples were taken on d 7 (TN), 8 (HS), 10 (HS), 17 (HS), and 18 (TN) during the Agricultural Research Complex segment. Cows in HS had higher RR and RT and water intake and lower dry matter intake and milk yield than these measures in TN. There was a treatment × environment interaction with cows fed OG having lower RR and RT and higher dry matter intake during peak thermal loads than CON. However, milk yield did not differ between groups. Cows fed OG had lower milk fat percent than CON (3.7 vs 4.3%) during HS. The SCC content of milk did not differ between treatment groups but rose in both groups during the REC phase following HS. Plasma insulin and plasma glucose levels were not different between groups. However, plasma insulin in both groups was lower during acute HS, then rose across the HS period, and was highest during the REC phase. Plasma cortisol levels were highest in all cows on the first day of HS (d 8) but were lower in cows fed OG compared with CON. However, plasma ACTH concentrations were elevated in OG-fed animals at all times samples were collected. Plasma ACTH was also elevated in cows fed both OG and CON during HS. Feeding OG reduced plasma cortisol during acute but not chronic HS and increased basal plasma ACTH, suggesting that OG treatment may alter the hypothalamic pituitary adrenal axis. [ABSTRACT FROM AUTHOR]

Omnigen-AF (OAF) increases leukocyte functions in immunosuppressed animal models and reduces incidence of infectious diseases in early lactating dairy cows, although its mode of action is still unclear. This study aims to provide a wider perspective of the metabolic effect of OAF to test its potential as a strategy to address metabolic disorders of the transition period. A group of 10 Holstein dairy cows were divided into 2 groups: The treated group (IMS; 5 cows) received 32.5 g of OAF twice a day (65 g d−1) as top-dress in the morning and afternoon feeds from −55 to 42 days from calving (DFC), whereas the control group (CTR; 5 cows) received no supplementation. From −62 to 42 DFC, body condition score, body weight, dry matter intake, rumination time and milk yield were measured; blood samples were collected weekly to assess a wide hematochemical profile and to test white blood cell functions by ex-vivo challenge assays. At 30 DFC, rumen fluid was collected and analyzed for pH, volatile fatty acids composition, urea nitrogen, and lactate contents. Data were submitted to ANOVA using a mixed model for repeated measures, including treatment, time, and their interaction as fixed effects. OAF decreased blood nonesterified fatty acids and beta hydroxybutyrate concentrations and increased rumination time in early lactation. Leukocytes from IMS cows had lower lactate production and lower glucose consumption after ex-vivo stimulation. OAF did not reduce the acute phase response indicators and reduced the blood concentrations of albumin and antioxidants after calving, suggesting impairment of hepatic functions related to protein synthesis and antioxidant management. Nevertheless, the lack of effect on bilirubin and liver enzymes refutes the possibility of severe liver damage occurring with OAF supplementation. Positive effects in reducing mobilization of body fats and ketogenesis and in increasing rumination time after calving suggest OAF effectiveness in preventing metabolic disorders of the transition period.

Mycobacterium tuberculosis remains one of the world's deadliest killers, with an annual death rate of ∼1.5 million. The medicinal effects of garlic have been well documented, and natural products have been shown to have antimycobacterial activity. The current study evaluated the efficacy of six Allium sativum L. polysulfide mixtures as antimycobacterial agents together with their cytotoxic, immunomodulatory, and hepatoprotective activities. The microtitre PrestoBlue assay was used to determine the minimum inhibitory concentrations (MIC). Cytotoxicity was evaluated by using peripheral blood mononuclear cells (PBMC). Excreted cytokine levels were determined by utilizing an enzyme-linked immunosorbent assay (ELISA), by exposing isolated PBMCs to varying concentrations of polysulfide mixtures. Human C3A liver cells were utilized in the hepatoprotective study, to assess the protective effect against the toxicity induced by acetaminophen. Samples with higher amounts of diallyl trisulfide (Sample G4) showed the highest antimycobacterial activity, exhibiting an MIC of 2.5 μg/mL against M. tuberculosis H37Rv. Five samples showed moderate toxicity in PBMC, with G1 showing no toxicity. The selective index of G4 was the highest, with a selectivity index close to one. Two samples, G3 and G6 containing higher amounts of diallyl tetrasulfide and lower amounts of diallyl trisulfide, showed >50% hepatoprotection. This is comparable to a hepatoprotective agent, Silymarin, which showed a hepatoprotective effect of 30% at the tested concentration. Diallyl tetrasulfide showed significant antimycobacterial activity. A combination of higher diallyl tetrasulfide and lower diallyl trisulfide was indicative of hepatoprotective activity. [ABSTRACT FROM AUTHOR]

We analyzed the effects of levamisole on stress and the innate immune responses of pacu ( Piaractus mesopotamicus ). A total of 300 fish (180 ± 1.27 g) were fed a diet containing levamisole hydrochloride (LHC) for 15 days, then distributed into the following groups: T0 (control group); T1 (100), T2 (150), T3 (300) and T4 (500) mg kg −1 LHC (15 fish per group and four replicates per treatment). After this, fish (n = 8 per treatment) were exposed to air for three minutes to simulate stress conditions and were then challenged with the bacterium Aeromonas hydrophila to stimulate the immune system. Fish were sampled at 1, 3 and 24 h after bacterial inoculation to measure plasma cortisol and glucose concentrations, the leukocyte respiratory burst (LRB), hemolytic activity of the complement system (HAC 50 ) and serum lysozyme activity (SLA). LHC attenuated the increase in plasma cortisol at 1 h (500 mg kg −1 ) and 3 h (300 mg kg −1 ) after air exposure and bacterial inoculation compared to control fish. The highest glucose concentrations were observed at 1 and 3 h after stress, which then returned to initial levels after 24 h, without any effect of LHC. The LHC 100 mg kg −1 dose increased LRB 1 h after inoculation and activated the HAC 50 3 h later. At 24 h, all LHC concentrations increased the HAC 50 . SLA was reduced after inoculation, throughout the experimental period, without an effect of levamisole. Our results indicate that the oral administration of levamisole for 15 days modulated circulating cortisol levels during the stress response and improved the innate immune response against A. hydrophila infection in pacu. [ABSTRACT FROM AUTHOR]

The main objective of this study was to evaluate the effect of peripartal administration of a commercially available nonspecific immune stimulant (mycobacterium cell wall fraction; MCWF [Amplimune, NovaVive Inc., Napanee, ON, Canada]) on the incidence of disease during early lactation and subsequent fertility of dairy cows. A second objective was to characterize the dynamics of circulating white blood cells (WBC) and metabolic markers following treatment administration. Cows in an United States Department of Agriculture (USDA) organic-certified dairy herd were blocked by parity and, based on sequential calving dates, randomly assigned to receive two injections (5 mL s.c.) of either a placebo (saline solution) as a control (CON; n = 71) or MCWF (n = 65) at enrollment (7 d before expected calving) and within 24 h after calving. Blood samples were collected from a subsample of the study population (MCWF = 16; CON = 18) for WBC count at enrollment, at day 2 post enrollment, and at days 1, 3, 7, and 14 after calving. Serum fatty acids, beta-hydroxybutyrate, and Ca concentrations were determined at days 1 and 7 postpartum (MCWF = 21; CON = 21). Main outcome variables included incidence risk of peripartal and early lactation health disorders and pregnancy at first artificial insemination (AI), at 100, and at 150 days in milk (DIM). In addition, the average daily milk yield up to 90 DIM and death and live culling before 305 DIM were compared. Treatment effects were assessed using multivariable logistic regression, time-to-event analyses, and repeated measures analysis of variance (ANOVA). A treatment effect on the incidence risk of some of the health disorders in the study was established. Incidence risk of metritis and clinical mastitis <28 DIM was smaller in MCWF than in CON cows (36.9% vs. 50.7% and 6.3% vs. 19.7%, respectively). On the contrary, the incidence risk of respiratory disease <28 DIM was smaller in CON (0%) than in MCWF (7.7%). Reproductive performance of multiparous cows was affected by MCWF administration: pregnancy at first AI and pregnancy at 100 and 150 DIM were greater in MCWF than in CON (35.6% vs. 19.2%; 51.1% vs. 25.0%; and 64.4% vs. 40.4%, respectively). Overall, median intervals from calving to pregnancy were 90 vs. 121 d in MCWF and CON cows, respectively. No treatment effects on the dynamics of circulating WBC or in postpartum metabolic status were established. No differences for milk yield or for the proportion of cows that survived up to 305 DIM were determined, although cows in MCWF left the herd earlier than cows in CON. In conclusion, incidence risks of metritis and mastitis in early lactation were smaller in cows receiving MCWF, whereas the incidence risk of respiratory disease was smaller in CON. Fertility significantly improved in MCWF compared with CON cows. As this study was performed in an organic-certified dairy, specific health and reproductive management practices may affect the external validity of the current findings., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ablation therapies have emerged as an effective tool for destroying cancerous tissue, but for advanced and disseminated tumors their application remains mainly a palliative measure. However, it is becoming increasingly clear that this limitation can be redressed by the use of intratumoral immune stimulating agents for amplifying potential antitumor immune responses that are induced by ablation therapies. A novel immune stimulating drug IP-001, a specific variant of the N-dihydrogalactochitosan (GC) family of molecules, has shown to be effective against metastatic tumors, when combined with different forms tumor ablation. It acts as a multi-function immune stimulant both by directly inhibiting cell membrane repair and recycling of ablation-damaged tumor cells, and indirectly by sequestering ablation-released tumor antigens, as well as recruiting and stimulating antigen presenting cells to induce a potent Th1 type T cell response against the cancer. In this review, we briefly discuss the current applications of local ablation for cancer treatment and the effects of GC in combination with other ablation therapies, a therapeutic approach that is pioneering the field of Interventional Immuno-Oncology (IIO). [ABSTRACT FROM AUTHOR]

Our objective was to evaluate the effects of a non-specific immune stimulant (IS) administered around transportation on health scores (HS), average daily gain (ADG), disease treatment and mortality of Jersey and Jersey-cross calves during the rearing period. Newborn calves (4 d ± 1) were randomly allocated to receive either 1 mL of saline (CON; n = 438), 1 mL of IS before transport (BTIS; n = 431), or 1 mL of IS immediately after transport (ATIS; n = 436). Calves were health scored weekly for 3 weeks after transport. The data were analyzed using multivariable linear mixed models and multivariable logistic regression models. Kaplan-Meier survival analysis was performed for time to event analysis. Treatment, birth weight, breed, site of birth, serum total solids, dam parity, season of enrollment, and metaphylaxis were offered to models. Differences in respiratory and fecal HS, and ADG between treatment groups were not statistically significant. A total of 196 (15.0%) calves were treated at least once for any disease and 52 calves were treated multiple times. The proportion of calves treated for respiratory disease and/or diarrhea were 14.4, 14.4, and 16.2% for BTIS, ATIS and CON groups, respectively. Although the differences in the likelihood of treatment for both respiratory disease and/or diarrhea during the first 9 weeks of life was not statistically different between groups, we observed that more calves in the control group received disease treatments around 15 days of age compared with calves that received IS. The likelihood of treatment for respiratory diseases alone during the first 30 days of life was smaller in the calves that received IS before transportation when compared to the control group. Only 18 (1.4%) calves died within the study period. The calf mortality likelihood was not statistically different between study groups; however, fewer calves in the IS groups died when compared to CON. In conclusion, the use of IS around transportation did not influence weekly HS, ADG, and the number of disease treatments during the rearing period, but administering IS before transportation resulted in fewer treatments of respiratory diseases during the first 30 days post-transport and marginally lower mortality rates during the rearing period., (Copyright © 2020 Omontese, Caixeta, Machado, Rendahl, Celestino, Menta, Paiva, Garcia-Muñoz and Masic.)

Human Vγ9Vδ2 T cells respond to microbial infections and malignancy by sensing diphosphate-containing metabolites called phosphoantigens, which bind to the intracellular domain of butyrophilin 3A1, triggering extracellular interactions with the Vγ9Vδ2 T cell receptor (TCR). Here, we examined the molecular basis of this "inside-out" triggering mechanism. Crystal structures of intracellular butyrophilin 3A proteins alone or in complex with the potent microbial phosphoantigen HMBPP or a synthetic analog revealed key features of phosphoantigens and butyrophilins required for γδ T cell activation. Analyses with chemical probes and molecular dynamic simulations demonstrated that dimerized intracellular proteins cooperate in sensing HMBPP to enhance the efficiency of γδ T cell activation. HMBPP binding to butyrophilin doubled the binding force between a γδ T cell and a target cell during "outside" signaling, as measured by single-cell force microscopy. Our findings provide insight into the "inside-out" triggering of Vγ9Vδ2 T cell activation by phosphoantigen-bound butyrophilin, facilitating immunotherapeutic drug design. • The crystal structure of HMBPP-bound intracellular BTN3A1 was determined at 1.97 Å • HMBPP forms hydrogen bonds with H 351 for efficient Vγ9Vδ2 T cell activation • An asymmetric intracellular dimer is involved in HMBPP-mediated γδ T cell activation • HMBPP doubles the binding force between extracellular BTN3A and Vγ9Vδ2 TCR Vγ9Vδ2 T cells sense tumor and microbial metabolites without MHC restriction. Yang et al. used a multifaceted approach to show how the highly potent microbial HMBPP binds to BTN3A1 and triggers inside-out signaling to activate Vγ9Vδ2 T cells. This study will have implications in emerging clinical applications of allogeneic Vγ9Vδ2 T cells. [ABSTRACT FROM AUTHOR]

Omnigen-AF (OAF) increases leukocyte functions in immunosuppressed animal models and reduces incidence of infectious diseases in early lactating dairy cows, although its mode of action is still unclear. This study aims to provide a wider perspective of the metabolic effect of OAF to test its potential as a strategy to address metabolic disorders of the transition period. A group of 10 Holstein dairy cows were divided into 2 groups: The treated group (IMS; 5 cows) received 32.5 g of OAF twice a day (65 g d -1 ) as top-dress in the morning and afternoon feeds from -55 to 42 days from calving (DFC), whereas the control group (CTR; 5 cows) received no supplementation. From -62 to 42 DFC, body condition score, body weight, dry matter intake, rumination time and milk yield were measured; blood samples were collected weekly to assess a wide hematochemical profile and to test white blood cell functions by ex-vivo challenge assays. At 30 DFC, rumen fluid was collected and analyzed for pH, volatile fatty acids composition, urea nitrogen, and lactate contents. Data were submitted to ANOVA using a mixed model for repeated measures, including treatment, time, and their interaction as fixed effects. OAF decreased blood nonesterified fatty acids and beta hydroxybutyrate concentrations and increased rumination time in early lactation. Leukocytes from IMS cows had lower lactate production and lower glucose consumption after ex-vivo stimulation. OAF did not reduce the acute phase response indicators and reduced the blood concentrations of albumin and antioxidants after calving, suggesting impairment of hepatic functions related to protein synthesis and antioxidant management. Nevertheless, the lack of effect on bilirubin and liver enzymes refutes the possibility of severe liver damage occurring with OAF supplementation. Positive effects in reducing mobilization of body fats and ketogenesis and in increasing rumination time after calving suggest OAF effectiveness in preventing metabolic disorders of the transition period.