Cisplatin (CP) chemotherapy is limited by nephrotoxicity, primarily involving tubular epithelial cell apoptosis. αB-crystallin (CryAB) is a small heat shock protein that plays a cytoprotective role in stressed kidneys but can also promote tumor progression. Its precise role and molecular mechanisms in CP-induced kidney injury remain largely unclear. This study highlighted the function of CryAB and its regulatory pathways in CP nephrotoxicity by employing in vitro models of rat renal tubular epithelial cells (NRK-52E) with CryAB gene knockdown/overexpression, and in vivo models of CryAB knockout/wild-type mice, followed by CP treatment. Apoptosis and key signaling pathways (NF-κB, MAPK, AKT) were evaluated in this study. The results indicated that CP treatment (20 µM) significantly upregulated CryAB expression in renal cells (p < 0.01) and triggered both apoptosis and MAPK activation. CryAB deficiency sensitized cells and mice to CP, exacerbating renal dysfunction, tubular injury, and apoptosis, as evidenced by increased Bax, cyt c release, and caspase-3 cleavage. Conversely, CryAB overexpression attenuated these effects. Furthermore, our findings suggest that the lack of CryAB favors the cytoplasmic retention of NF-κB, and that CryAB status can influence MAPK signaling, pointing to a potential regulatory loop. Additionally, CP-induced AKT phosphorylation was diminished in CryAB-deficient models. Therefore, CryAB may exert a cytoprotective role in CP nephrotoxicity, potentially mitigating tubular apoptosis by modulating the mitochondrial apoptotic pathway, supporting NF-κB-mediated survival signaling, and cross-talking with MAPK and AKT pathways. Our findings suggest that CryAB serves as an important regulator of renal cell fate and a potential therapeutic target for mitigating CP-induced kidney injury.

In intensive poultry farming, environmental stress, pathogen infections, and noise can negatively impact growth or cause sudden death, leading to economic losses. The prevalent use of antibiotics as feed additives to prevent diseases in broilers has raised concerns about antibiotic resistance and highlighted the need for safer and more effective alternatives. Carnosic acid (CA), a bioactive compound derived from rosemary, exhibits notable pharmacological properties, including anti-inflammatory and antioxidant effects. This study investigates CA's efficacy in mitigating lipopolysaccharide (LPS)-induced heart inflammation in broilers. Broilers were pretreated with CA at varying doses (20, 40, and 80 mg/kg) for 7 days then exposed to LPS (200 mg/kg) for 24h to induce an inflammatory response. LPS treatment increased the levels of the cardiac damage markers creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) and inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS), but these effects were markedly decreased in CA-pretreated poultry. Histopathological analysis indicated that CA mitigated myocardial fiber rupture and inflammatory cell infiltration. Immunohistochemistry showed that CA sustained high expression levels of the protective protein crystallin alpha B (CRYAB), the expression of which was reduced by LPS. Mechanistic studies demonstrated that CA regulates key inflammatory signaling pathways via inhibiting LPS-induced activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) by reducing the phosphorylation of p65 and inhibitor of nuclear factor kappa-B alpha (IκBα). Additionally, CA attenuated mitogen-activated protein kinase (MAPK) pathway activation, as evidenced by decreased phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 in the CA-treated groups compared to the LPS-only groups. These findings suggest that CA exerts a protective effect against LPS-induced cardiac inflammation by enhancing CRYAB expression and modulating the NF-κB and MAPK pathways. Importantly, the findings emphasize CA's potential as a natural feed additive to enhance cardiac health in poultry and present a promising alternative to conventional antibiotics in livestock management. Further research is needed to investigate its broader applications in animal health and other inflammatory conditions.

Intensive poultry farming faces challenges like gut inflammation in the absence of antibiotics, resulting in reduced productivity, heightened susceptibility to enteric diseases, and other complications. Alternative strategies are needed to manage inflammation and maintain sustainable poultry production. Yaks living in high-altitude hypoxic environments have specialized gut microbes. However, yak probiotics remain largely uncharacterized. We previously isolated a strain of Bacillus pumilus (named TS2) from yaks and demonstrated its potential as a probiotic in vitro. Therefore, in this study, we evaluated the in vivo growth-promoting, antioxidant, immune, and anti-inflammatory effects of Bacillus pumilus isolated from yaks in broilers. We demonstrated the safety of TS2 isolated from yaks in broilers. Furthermore, we found that TS2 increased the average daily weight gain (ADWG) and reduced the feed conversion ratio (FCR). Supplementation with TS2 also improved the mucosal morphology, the ratio of villi to crypt cells, and enzyme activity. High-throughput sequencing showed that the abundance of Lactobacillus was higher in the TS2 treated broilers. Importantly, the serum level of malondialdehyde (MDA) was reduced and the levels of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were increased in the low-dose TS2 group, while the inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were downregulated compared with the control group. We demonstrated that TS2 supplementation can increase the overall growth performance and ameliorate the blood parameters related to inflammation and immunity in broilers.

Inflammatory processes are often accompanied by oxidative stress and lipid peroxidation, which might lead to cellular and organ damage. Carnosic acid (CA), an active component found in rosemary, exhibits pharmacological properties including antioxidative, anti-inflammatory, and antiviral effects. The aim of this research was to investigate whether CA can mitigate lipopolysaccharide (LPS)-induced oxidative stress and inflammatory responses in poultry and to understand its underlying mechanisms. We administered CA to broiler chickens via oral gavage and treated them with LPS, followed by analysis of the effects of different dosages of CA on body weight, antioxidative capacity, and inflammatory factors. Carnosic acid had no significant impact on the body weight of broiler chickens. However, serum analysis indicated that the middle dose of CA effectively enhanced the antioxidative capacity and reduced levels of oxidative stress and inflammation-related factors. Moreover, in the liver, CA demonstrated the ability to regulate the expression of proteins such as heat shock protein 60 (HSP60), heat shock protein 70 (HSP70), and P38 mitogen-activated protein kinase (P38), suggesting its protective role against liver damage induced by LPS. In the intestinal tract of broiler chickens, CA regulated the expression and localization of proteins including HSP60, HSP70, NFE2 like bZIP transcription factor 2 (Nrf2), and P38, while also influencing the expression of inflammatory markers such as protein tyrosine phosphatase receptor type C (CD45), and connexin (Cx). These findings revealed the potential protective mechanisms of CA in alleviating oxidative stress and inflammatory damage induced by LPS in poultry. Carnosic acid notably enhanced the chickens' antioxidative capacity by modulating the expression of key proteins, thereby reducing oxidative stress and inflammatory response levels. This study provides a deeper comprehension of the protective mechanisms of CA and its potential impact on avian health.

Heat stress impacts male reproduction in animal husbandry. Carnosic acid (CA), a potent antioxidant, mitigates oxidative stress and apoptosis. alpha B-crystallin, a small heat shock protein, regulates apoptosis and oxidative stress. This study examines the protective effects of CA on the testis in wild-type and alpha B-crystallin knockout mice under heat stress. CA pretreatment increased testosterone levels and preserved testicular structure in wild-type mice, but no changes in knockout mice. CA reduced Hsp27, Hsp70, and cleaved caspase-3 levels, while knockout mice showed increased cleaved caspase-3. These results suggest that CA protects the testis by modulating heat shock and apoptosis-related proteins.

Heat shock proteins (HSPs) play an important role in all living organisms under stress conditions by acting as molecular chaperones. The expression of different HSPs during stress varies depending on their protective functions and anti-apoptotic activities. The application of HSPs improves the efficiency and decreases the economic cost of animal breeding. By upregulating the expression of HSPs, feed supplements can improve stress tolerance in farm animals. In addition, high expression of HSPs is often a feature of tumor cells, and inhibiting the expression of HSPs is a promising novel method for killing these cells and treating cancers. In the present review, the findings of previous research on the application of HSPs in animal breeding and veterinary medicine are summarized, and the knowledge of the actions of HSPs in animals is briefly discussed.

This study investigates whether Bacillus pumilus TS1 improves growth performance and alleviates inflammatory damage in broilers and explored its feasibility as an antibiotic alternative. We divided 240 one-day-old AA308 white-finned broilers into five groups (con, LPS, TS1L + LPS, TS1M + LPS and TS1H + LPS). The TS1L + LPS, TS1M + LPS and TS1H + LPS groups were fed TS1 for 15 days by gavage. The LPS, TS1L + LPS, TS1M + LPS and TS1H + LPS groups were injected intraperitoneally with 1 mg/kg LPS for three days. We investigated the probiotic and anti-inflammatory activities by measuring body weight, sequencing the intestinal flora and examining the structure of tissues by using pathological stain, real-time PCR, Western blotting and immunohistochemical detection. TS1 could improve growth performance and intestinal flora composition, also reduced different organ damage and inflammatory cytokine expression in serum and organs. The mechanism may involve upregulating HSP60 and HSP70 expression, targeting and regulating Nrf2 and P38 MAPK and modulating NF-κB and HO-1 expression at the transcriptional level in different organs. B. pumilus TS1 alleviated Inflammatory injury caused by LPS and attenuated the inflammatory response in broilers, and these effects were achieved through MAPK and Nrf2 regulation of HSPs/HO-1 in different organs. The above results suggested broilers fed with TS1 could release the LPS caused organ damage, and the most suggested dosage was 1.4 × 108 CFU/mL.

Background In the current context of reduced and limited antibiotic use, several pathogens and stressors cause intestinal oxidative stress in poultry, which leads to a reduced feed intake, slow or stagnant growth and development, and even death, resulting in huge economic losses to the poultry breeding industry. Oxidative stress in animals is a non-specific injury for which no targeted drug therapy is available; however, the health of poultry can be improved by adding appropriate feed additives. Bacillus pumilus , as a feed additive, promotes growth and development and reduces intestinal oxidative stress damage in poultry. Heat shock protein 70 (HSP70) senses oxidative damage and repairs unfolded and misfolded proteins; its protective effect has been widely investigated. Mitogen-activated protein kinase/protein kinase C (MAPK/PKC) and hypoxia inducible factor-1 alpha (HIF-1α) are also common proteins associated with inflammatory response induced by several stressors, but there is limited research on these proteins in the context of poultry intestinal Salmonella Enteritidis (SE) infections. In the present study, we isolated a novel strain of Bacillus pumilus with excellent performance from the feces of healthy yaks, named TS1. To investigate the effect of TS1 on SE-induced enteritis in broilers, 120 6-day-old white-feathered broilers were randomly divided into four groups (con, TS1, SE, TS1 + SE). TS1 and TS1 + SE group chickens were fed with 1.4 × 10 7 colony-forming units per mL of TS1 for 15 days and intraperitoneally injected with SE to establish the oxidative stress model. Then, we investigated whether TS1 protects the intestine of SE-treated broiler chickens using inflammatory cytokine gene expression analysis, stress protein quantification, antioxidant quantification, and histopathological analysis. Results The TS1 + SE group showed lower MDA and higher GSH-Px, SOD, and T-AOC than the SE group. TS1 alleviated the effects of SE on intestinal villus length and crypt depth. Our results suggest that SE exposure increased the expression of inflammatory factors (IL-1β, IL-6, TNF-α, IL-4, and MCP-1), p38 MAPK, and PKCβ and decreased the expression of HSP60, HSP70, and HIF-1α, whereas TS1 alleviated these effects. Conclusions Bacillus pumilus TS1 alleviated oxidative stress damage caused by SE and attenuated the inflammatory response in broilers through MAPK/PKC regulation of HSPs/HIF-1α.

Streptococcus agalactiae is a contagious pathogen that causes bovine mastitis worldwide, resulting in considerable economic losses. In this study, we isolated 42 S. agalactiae strains in 379 milk samples from cows with subclinical mastitis on 15 dairy farms in 12 Chinese provinces. Analysis based on capsular typing and multilocus sequence typing, combined with patterns of virulence gene scanning and antimicrobial resistance, identified the lineages and populations of the isolates. We grouped the 42 isolates into 7 sequence types belonging to 6 clonal complexes, mainly CC103 (31/42 isolates; 73.8%). We identified an ST-23 strain named Sa 129 for the first time on Chinese dairy farms—this strain is usually associated with human isolates. Capsular types Ia and II were predominant in capsular typing. The prevalence of virulence profile 1 (bibA, cfb, cspA, cylE, fbsA, fbsB, hylB, and pavA) was 64.3%, and represented the main trend in China. With respect to antimicrobial resistance, most isolates were susceptible to β-lactams, rifamycin, glycopeptides, and oxazolidone; resistance to several antimicrobial agents, including lincomycin, clindamycin, and doxycycline, varied in 4 different regions. Our research provides a profile for the molecular epidemiology, multilocus sequence typing, antimicrobial resistance, and virulence gene clustering of S. agalactiae, and may be beneficial for the clinical monitoring, prevention, and control of mastitis in dairy cattle.

为探讨热应激对鸡肺脏组织损伤的影响,将60只35日龄SPF鸡随机分为对照组,热应激1、2、3、5、10 h组,每组10只,试验开始后环境温度迅速从25℃升高到35 ℃,观察热应激组鸡临床症状,热应激结束迅速剖杀、取病料,检测血清pH值、乳酸脱氢酶(LDH)、钾离子和钙离子浓度,石蜡切片检测肺脏组织结构,Western blot检测肺脏组织中热休克蛋白(HSPs)表达量.结果显示:与对照组相比,热应激组血清pH值显著升高(P＜0.05),LDH水平均极显著升高(P＜0.01),随着热应激时间增加,血钾和血钙浓度开始降低,热应激5、10h后血钾和血钙浓度显著减低(P＜0.05);病理组织学结果显示热应激后,肺组织内血管充血,肺房结构基本完整,热应激5h后肺房内有大量的红细胞存在,热应激10 h肺房内的异物减少,但肺上皮细胞大量脱落,组织结构损伤严重;Western blot结果显示与对照组相比,HSP27和HSP72表达量极显著升高(P＜0.01)HSP60表达量在热应激1 h后显著升高(P＜0.05),随后呈降低的趋势,HSP90表达量在热应激5h后显著升高(P＜0.05),随后呈降低的趋势,HSC70表达量无明显变化.热应激可对鸡呼吸系统造成损伤,提高肺脏HSPs表达量.

In order to explore the function of vitamin C (VC) and VC-Na in the relief of heat stress injury in chicken cardiomyocytes, 150 30-day-old specific-pathogen-free chickens were randomly divided into a control group (fed normal drinking water), a VC group (50 μg/mL VC in drinking water), and a VC-Na group (50 μg/mL VC-Na in drinking water). After 7 days of adaptation feeding, the chickens were subjected to heat stress at 40 ± 2 °C and 60%-70% humidity for 0, 1, 3, 5, and 10 h, respectively, and the sera and heart tissues of the chickens were collected immediately at the corresponding heat stress time points. The effects of VC and VC-Na supplementation on the relief of chicken myocardial cell injury following heat stress was studied by detecting the levels of LDH, CK, CK-MB, and total antioxidant capacity (T-AOC) in the sera, and through histopathological analysis and the expression of CRYAB, Hsp27, and Hsp70 in the myocardial cells. The results showed that supplementing with 50 μg/mL VC or VC-Na significantly reduced the levels of LDH, and CK-MB in serum as well as heat-stress-induced granular and vacuolar degeneration, myocardial fiber breakage, and cell necrosis, indicating effective resistance to heat-stress damage. Additionally, the levels of T-AOC in serum were increased in the VC and VC-Na groups, suggesting enhancing of antioxidant capacity. Furthermore, the expression of CRYAB were induced at 0, 3, 5, and 10 h (P < 0.01) in both VC and VC-Na group, and that of Hsp70 were induced at 0 h (P < 0.05) in VC group and at 0, 3, 5, 10 h (P < 0.01) in VC-Na group. Thus, supplementing chicken diets with VC or VC-Na presented heat-stress damage resistance by enhancing antioxidant capacity and inducing expression of CRYAB and Hsp70.

Hormones have become a useful therapeutic aspect of clinical endocrinology but how to use them to optimize the health benefits and avoid adverse effects is a major challenge. Estrogen is an indispensable hormone for proper biological functioning but is also implicated with the pathology of both the reproductive and non-reproductive tissues. Abnormal estrogen receptor signaling may increase the risk of development of a variety of diseases including colorectal cancer (CRC). Estrogen receptor beta (ERβ) is the predominant subtype in the colonic epithelium and confers the anti-tumor effect through various mechanisms. Many investigators have embarked on the search for the biological mechanisms by which estrogen and estrogen-like compounds may influence the pathogenesis of CRC. This review explores the recent findings on the therapeutic role of ERβ in the colonic epithelium as a prospective candidate for targeted endocrine therapy in CRC.

Heat stress is a major stressor that can lead to male reproductive dysfunction. Sertoli cells play a crucial role in spermatogenesis by providing germ cells with structural and nutritional support, and contributing to blood-testis barrier formation. Vitamin C (Vc) is an antioxidant capable of neutralizing reactive oxygen species and preventing lipid peroxidation widely used because it is inexpensive and highly accessible. In the present study, we investigated the protective effect of Vc on TM4 cells following heat stress. Pretreatment with Vc could effectively inhibit apoptosis (p < 0.01), lipid peroxidation, and lactate dehydrogenase (LDH) activity. However, a significant increase in the malondialdehyde (MDA) level and LDH activity (p < 0.01) was observed in TM4 cells without Vc-pretreatment, in conjunction with vacuole degeneration and karyopyknosis. In addition, both the messenger RNA and protein levels of CryAB, Hsp27, Hsp70, and Hsp110 substantially increased in the 3 and 12 hr recovery groups (p < 0.01). Vc also prevented microtubule aggregation following heat stress. These results suggest that pretreatment with Vc-protected TM4 cells against heat stress by reducing the level of oxidative stress and inducing heat shock protein expression.

In the original publication of the article, one of the images was selected by mistake in Fig. 3 (HS + ASA, 5 h). The correct version of Fig. 3 is given in this correction.

CRYAB is a small heat shock protein (sHSP) that has previously been shown to protect the heart against various cellular stresses; however, its precise function in myocardial cell injury caused by heat stress remains unclear. This study aimed to investigate the molecular mechanism by which CRYAB protects cardiomyocytes against heat stress. We constructed two H9C2 cell lines that stably express CRYAB protein to differing degrees: CRYAB-5 and CRYAB-7. Both CRYAB-5 and CRYAB-7 showed significantly reduced granular degeneration and vacuolar degeneration following heat stress compared to control cells. In addition, CRYAB overexpression in H9C2 cells relieved cell cycle proportion at the G0/G1 phase following heat stress compared to control cells. These protective effects were associated with the level of CRYAB protein expression. Our immunofluorescence analysis showed CRYAB could translocate from the cytoplasm to the nucleus under heat stress conditions, but that CRYAB co-localized with F-actin (which accumulates under stress conditions). Indeed, overexpression of CRYAB significantly reduced the aggregation of F-actin in H9C2 cells caused by heat stress. Furthermore, overexpressing CRYAB protein significantly reduced the apoptosis of cardiomyocytes induced by heat stress, likely by reducing the expression of cleaved-caspase 3. Collectively, our results show overexpression of CRYAB significantly increases the heat resistance of H9C2 cardiomyocytes, likely by reducing F-actin aggregation (thus stabilizing the cytoskeleton), regulating the cell cycle, and preventing caspase-mediated apoptosis.

In this study, we investigated the function of co-enzyme Q10 (Q10) in autophagy of primary chicken myocardial cells during heat stress. Cells were treated with Q10 (1 μΜ, 10 μΜ, and 20 μM) before exposure to heat stress. Pretreatment of chicken myocardial cells with Q10 suppressed the decline in cell viability during heat stress and suppressed the increase in apoptosis during heat stress. Treatment with 20 μM Q10 upregulated autophagy-associated genes during heat stress. The expression of LC3-II was highest in cells treated with 20 μM Q10. Pretreatment with Q10 decreased reactive oxygen species (ROS) levels during heat stress. The number of autophagosomes was significantly increased by 20 μM Q10 treatment, as demonstrated by electron microscopy or monodansylcadaverine (MDC) fluorescence. SQSTM1 accumulation was diminished by Q10 treatment during heat stress, and the number of LC3II puncta was increased. Treatment with 20 μM Q10 also decreased the activation of the PI3K/Akt/mTOR pathway. Our results showed that co-enzyme Q10 can protect primary chicken myocardial cells by upregulating autophagy and suppressing the PI3K/Akt/mTOR pathway during heat stress.

We investigated the effects of co-enzyme Q10 (Q10) and acetyl salicylic acid (ASA) on expression of Hsp70 in the protection of primary chicken myocardial cells during heat stress. Western blot analysis showed that Q10 and ASA accelerated the induction of Hsp70 when chicken myocardial cells were exposed to hyperthermia. In the absence of heat stress, however, neither Q10 nor ASA are able to upregulate Hsp70 expression. Analysis of enzymes that respond to cellular damage and pathological examination revealed that ectopic expression of ASA and Q10 alleviate cellular damage during heat stress. Quantification of heat shock factors (HSF) indicated that treatment of ASA increased the expression of HSF-1 and HSF-3 during heat stress. Treatment with Q10 resulted in the elevation of HSF-1 expression. Expression of HSF-2 and HSF-4 was not affected by ASA or Q10. Subcellular distribution analysis of HSF-1 and HSF-3 showed that in response to heat stress ASA promoted nuclear translocation of HSF-1 and HSF-3, while Q10 promoted only HSF-1 nuclear translocation. Chromatin immunoprecipitation (ChIP) analysis indicated that HSF-1 occupies the Hsp70 promoter in chicken primary myocardial cells during heat stress and under normal conditions, while HSF-3 occupies the Hsp70 promoter only during heat stress. Real-time PCR analysis revealed that ASA induces HSF-1 and HSF-3 binding to Hsp70 HSE, while Q10 only induces HSF1 binding to Hsp70 HSE, in agreement with the impact of HSF1 and HSF3 silencing on Hsp70 expression. These data demonstrate that ASA and Q10 both induce the expression of Hsp70 to protect chicken primary myocardial cells during heat stress, but through distinct pathways.

In this report, we investigate the protective mechanism of co-enzyme Q10 on chicken primary myocardial cells during heat stress. Morphological observations indicate that addition of co-enzyme Q10 protects myocardial cells from heat stress, reduces the damage of mitochondria and nucleus, and decreases the mean number of vacuolated mitochondria. We have previously shown that co-enzyme Q10 can protect myocardial cells by upregulating the expression of Hsp70. Therefore, signaling pathways involved in this process were explored. No changes of total MAPK protein (P38MAPK, JNK, ERK) expression in the experimental groups were detected, with the exception of total JNK1. Co-enzyme Q10 failed to increase the expression of JNK1 compared to the HS group which was treated with heat stress only. Addition of Q10 upregulated the expression of p-P38MAPK, p-JNK, and p-ERK1. Inhibitors of P38MAPK and JNK, SB203580 and SP600125, respectively, weakened the upregulation of Hsp70 by co-enzyme Q10, indicating that MAPK pathways participate in the Hsp70 upregulation by co-enzyme Q10. Co-enzyme Q10 upregulates the expression of p-MEK3/6 and p-MEK4, but not p-MEK7 during heat stress. Expression of p-PKCα and p-PKCβ1 was also elevated following the addition of co-enzyme Q10 during heat stress, and addition of PKC inhibitors decreased the expression of Hsp70 induced by co-enzyme Q10. This confirms that PKC is also associated with the upregulation of Hsp70. In HS+Q10 group, addition of SP600125 or SB203580 could increase cell apoptosis under heat stress. Our results suggest that co-enzyme Q10 upregulates the expression of Hsp70 during heat stress to protect chicken primary myocardial cells via the PKC-MEK3/4/6-P38MAPK/JNK pathways.