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Cryptorchidism, the absence of one or both testicles in the scrotum, is the most common anomaly of genitourinary tract in males. The pathogenesis of undescended testes is unknown however the role of inflammation, tissue remodeling and oxidative stress is postulated. The aim of this study was to explore the role of HSP-70, MMP-3, MMP-17 and IL-8 in possible pathogenic pathways connected with cryptorchidism. Cryptorchid patients with high scrotal and inguinal canal localization were included. The study group consisted of 63 patients aged 12–24 months, whereas the control group included 17 healthy infants with the same demographic characteristics. The analysis of plasma samples was carried out using ELISA enzyme-linked immunosorbent assay technique. The plasma concentration of MMP-17 in boys with cryptorchidism was significantly higher compared to the control group (p = 0.0365). The concentration of plasma IL-8, MMP-3, and HSP-70 in boys with cryptorchidism increased in comparison to the control group but these increases were not statistically significant (p > 0.05). A positive correlation was found between plasma MMP-17 and HSP-70 concentration (r = 0.5153; p < 0.0001). Our results demonstrate that MMP-17 and HSP-70 might be involved in pathogenesis of cryptorchidism and are in line with current knowledge that high temperature has a negative influence on male gonads. [ABSTRACT FROM AUTHOR]

Abstract\nHIGHLIGHTSIn the era of global climate change, five cardinal oilseed mustards such as Brassica juncea, Brassica nigra, Brassica rapa, Brassica carinata, and Brassica napusare at alarming risk. Indeed, heat stress adversely affects their survival potential, growth rate, metabolism, yield, productivity, and oil content. To withstand extreme temperature by supplementing more top-notched genetically engineered thermostable mustard crops, we need to understand the differential expression patterns of heat shock proteins (HSPs), transcription factors (e.g. HSFs, NAC, DREB) and growth regulators as well as the transcriptional modulator network between HSPs and other chaperone proteins (e.g. calnexin, protein kinases). Furthermore, some HSPs initiate the degradation of misfolded and denatured proteins while others interact and bind to numerous types of folding intermediates and inhibit misfolded proteins from aggregating and promote refolding and activation of non-native and other chaperone proteins that have initially aggregated. A condensed version of the information on the interactions between HSPs is presented in this review and other chaperone like proteins along with the comprehensive knowledge of their scavenging interaction and modulation under elevated temperature conditions in oilseed mustard crop varieties to develop thermo-resilient mustard crops.Different varieties of mustard are susceptible to heat stress.Five predominant varieties of oilseed mustard are at high risk due to increase in temperature stress worldwide.Heat shock proteins(HSPs) and molecular co-chaperones altogether provide a certain level of thermostability to these plant species.Positive feedback loops have been identified between HSPs, heat shock factors (HSFs), and other co-chaperones during heat stress condition.Expression pattern of each HSP and co-chaperone of oilseed mustards during or following heat stress have been identified.One of the reasons behind HSPs activation during heat stress is an increase in reactive oxygen species (ROS) level.Different varieties of mustard are susceptible to heat stress.Five predominant varieties of oilseed mustard are at high risk due to increase in temperature stress worldwide.Heat shock proteins(HSPs) and molecular co-chaperones altogether provide a certain level of thermostability to these plant species.Positive feedback loops have been identified between HSPs, heat shock factors (HSFs), and other co-chaperones during heat stress condition.Expression pattern of each HSP and co-chaperone of oilseed mustards during or following heat stress have been identified.One of the reasons behind HSPs activation during heat stress is an increase in reactive oxygen species (ROS) level. [ABSTRACT FROM AUTHOR]

Heat stress poses a significant threat to grain yield. As an α2 subunit of the 26S proteasome, TT1 has been shown to act as a critical regulator of rice heat tolerance. However, the heat tolerance mechanisms mediated by TT1 remain elusive. In this study, we unveiled that small ubiquitin-like modifier (SUMO)-conjugating enzyme 1 (SCE1), which interacts with TT1 and acts as a downstream component of TT1, is engaged in TT1-mediated 26S proteasome degradation. We showed that SCE1 functions as a negative regulator of heat tolerance in rice, which is associated with its ubiquitination modification. Furthermore, we observed that small heat-shock proteins (sHSPs) such as Hsp24.1 and Hsp40 can undergo SUMOylation mediated by SCE1, leading to increased accumulation of sHSPs in the absence of SCE1. Reducing protein levels of SCE1 significantly enhanced grain yield under high-temperature stress by improving seed-setting rate and rice grain filling capacity. Taken together, these results uncover the critical role of SCE1 in the TT1-mediated heat tolerance pathway by regulating the abundance of sHSPs and SUMOylation, and ultimately modulating rice heat tolerance. These findings underscore the great potential of the TT1–SCE1 module in improving the heat tolerance of crops. This study reveals the pivotal role of SCE1, a SUMO E2 enzyme in TT1-mediated thermotolerance by modulating the abundance of small heat-shock proteins and SUMO modification. The findings implicate the great potential of the TT1–SCE1 module in integrating ubiquitination and SUMOylation, thereby serving as a valuable genetic target for enhancing heat tolerance in crops. [ABSTRACT FROM AUTHOR]

SUMMARY: HSP90Cs are essential molecular chaperones localized in the plastid stroma that maintain protein homeostasis and assist the import and thylakoid transport of chloroplast proteins. While HSP90C contains all conserved domains as an HSP90 family protein, it also possesses a unique feature in its variable C‐terminal extension (CTE) region. This study elucidated the specific function of this HSP90C CTE region. Our phylogenetic analyses revealed that this intrinsically disordered region contains a highly conserved DPW motif in the green lineages. With biochemical assays, we showed that the CTE is required for the chaperone to effectively interact with client proteins PsbO1 and LHCB2 to regulate ATP‐independent chaperone activity and to effectuate its ATP hydrolysis. The CTE truncation mutants could support plant growth and development reminiscing the wild type under normal conditions except for a minor phenotype in cotyledon when expressed at a level comparable to wild type. However, higher HSP90C expression was observed to correlate with a stronger response to specific photosystem II inhibitor DCMU, and CTE truncations dampened the response. Additionally, when treated with lincomycin to inhibit chloroplast protein translation, CTE truncation mutants showed a delayed response to PsbO1 expression repression, suggesting its role in chloroplast retrograde signaling. Our study therefore provides insights into the mechanism of HSP90C in client protein binding and the regulation of green chloroplast maturation and function, especially under stress conditions. [ABSTRACT FROM AUTHOR]

In light of the escalating global concern regarding adaptation and resilience to elevated temperatures due to climate change, this experiment was designed to assess the thermo-physiological attributes of two native sheep breeds (Najdi and Naimi) and to delineate potential genetic factors conferring heat tolerance amidst acute exposure to elevated ambient temperatures. Meteorological and thermo-physiological parameters were scrutinized at distinct intervals (0 min, 30 min, 120 min, 24 hr, and 48 hr), alongside the analysis of heat-responsive gene expression at 0 min, 30 min, and 120 min, following the exposure of nine healthy male lambs from each breed (mean body weight: 25 kg; age: 4 months) to a bio-meteorologically-simulated environment, maintaining an average ambient temperature of 45 °C (approximately 93 units in the temperature-humidity index). In addition, blood samples were collected from each lamb, with total RNA isolated and purity assessed, followed by qRTPCR analysis of 16 heat stress candidate genes using validated primers and standardized thermocycling protocols, including controls to ensure accuracy. Data were analyzed using statistical methods, including PROC GLM and PROC MEANS in SAS, one-way ANOVA, and pairwise differences with the LSD test for significance, while gene expression differences were calculated using the comparative Ct method and 2 (-Ct) for relative quantification. The findings elucidate that the Najdi breed manifests heightened thermotolerance relative to the Naimi breed, as evidenced by diminished indicators of heat stress, encompassing skin temperature, respiratory rate, packed cell volume, adaptability coefficient, serum total protein, glucose levels, and triiodothyronine concentration. Moreover, analysis of gene expression patterns revealed widespread activation of heat stress-responsive genes in both breeds under thermal stress conditions; however, Najdi lambs consistently exhibited elevated expression levels of these genes compared to their Naimi counterparts. Notably, genes including HSP90AB1, HSPB6, HSF1, STIP1, HSP60, HSP90, and HSPB1 demonstrated particularly pronounced upregulation in Najdi lambs. In conclusion, the integrative thermo-physiological and molecular profiling highlights the superior thermotolerance and evolutionary adaptation of the Najdi breed to the hot climate of the KSA, in contrast to the Naimi breed. [ABSTRACT FROM AUTHOR]

Background: Toxoplasma gondii is an opportunistic pathogenic protozoan that infects all warm-blooded animals, including humans, and causes zoonotic toxoplasmosis. The bradyzoite antigen 1 (BAG1), known as heat-shock protein (HSP)30, is a specific antigen expressed during the early stage of T. gondii tachyzoite–bradyzoite conversion. Methods: A bag1 gene knockout strain based on the T. gondii type II ME49 was constructed and designated as ME49Δbag1. The invasion, proliferation, and cyst formation efficiency in the cell model and survival in the mouse model were compared between the ME49 and ME49Δbag1 strains after infection. Quantitative polymerase chain reaction (qPCR) was used to detect the transcriptional level of important genes, and western-blot was used to detect protein levels. Results: ME49Δbag1 displayed significantly inhibited cyst formation, although it was not completely blocked. During early differentiation induced by alkaline and starvation conditions in vitro, the proliferation of ME49Δbag1 was significantly accelerated relative to the ME49 strain. Meanwhile, the transcription of the HSP family and bradyzoite formation deficient 1 (bfd1) were significantly enhanced. The observed upregulation suggests a compensatory mechanism to counterbalance the impaired stress responses of T. gondii following bag1 knockout. On the other hand, the elevated transcription levels of several HSP family members, including HSP20, HSP21, HSP40, HSP60, HSP70, and HSP90, along with BFD1, implied the involvement of alternative regulatory factors in bradyzoite differentiation aside from BAG1. Conclusions: The data suggested that when bag1 was absent, the stress response of T. gondii was partially compensated by increased levels of other HSPs, resulting in the formation of fewer cysts. This highlighted a complex regulatory network beyond BAG1 influencing the parasite's transformation into bradyzoites, emphasizing the vital compensatory function of HSPs in the T. gondii life cycle adaptation. [ABSTRACT FROM AUTHOR]

Background: Primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) are distinct hematological malignancies of B-cell origin that share many biological, molecular, and clinical characteristics. In particular, the JAK/STAT signaling pathway is a driver of tumor development due to multiple recurrent mutations, particularly in STAT6. Furthermore, the XPO1 gene that encodes exportin 1 (XPO1) shows a frequent point mutation (E571K) resulting in an altered export of hundreds of cargo proteins, which may impact the success of future therapies in PMBL and cHL. Therefore, targeted therapies have been envisioned for these signaling pathways and mutations. Methods: To identify novel molecular targets that could overcome the treatment resistance that occurs in PMBL and cHL patients, we have explored the efficacy of a first-in-class HSP110 inhibitor (iHSP110-33) alone and in combination with selinexor, a XPO1 specific inhibitor, both in vitro and in vivo. Results: We show that iHSP110-33 decreased the survival of several PMBL and cHL cell lines and the size of tumor xenografts. We demonstrate that HSP110 is a cargo of XPO1wt as well as of XPO1E571K. Using immunoprecipitation, proximity ligation, thermophoresis and kinase assays, we showed that HSP110 directly interacts with STAT6 and favors its phosphorylation. The combination of iHSP110-33 and selinexor induces a synergistic reduction of STAT6 phosphorylation and of lymphoma cell growth in vitro and in vivo. In biopsies from PMBL patients, we show a correlation between HSP110 and STAT6 phosphorylation levels. Conclusions: These findings suggest that HSP110 could be proposed as a novel target in PMBL and cHL therapy. [ABSTRACT FROM AUTHOR]

The supplementation of aquafeed with probiotics is recommended for feasible aquaculture activities. Therefore, the aim of current study was to investigate the potential effects of probiotics on growth performance, feed utilization, biochemical attributes, redox status and immunity response as well as the transcription of heat‐shock protein 70 (HSP70) and insulin‐like growth factor‐1 (IGF‐1) genes of Nile tilapia (Oreochromis niloticus; n = 120). Fish with an initial weight of 8.17 ± 0.02 g/fish were randomly divided into four treatment groups and were fed diets containing 0, 0.5, 1 and 1.5 mg immunobacteryne (IMB)/kg diet respectively. Dietary IMB at 1.5 g/kg diet significantly improved the growth performance, feed consumption and growth hormone secretion of the experimental fish (p < 0.05). The 1 or 1.5 g IMB/kg diet boosted phagocytic activities and innate immune response. Serum total protein, total cholesterol, triglycerides and glucose were significantly increased in the groups that were fed 1 and 1.5 mg IMB/kg diet compared to the control (p < 0.05). Meanwhile, the levels of uric acid, creatinine, liver enzymes (aspartate transaminase and alanine transaminase) and cortisol hormone were significantly reduced in the aforementioned treated groups compared to the control (p < 0.05). All fish fed IMB‐supplemented diet showed a significant increase in the expression of IGF‐1 gene, while the transcription of HSP70 was significantly decreased (p < 0.05). In conclusion, the dietary inclusion of IMB (1 g/kg diet) enhanced growth promoters, feed efficacy, blood biochemical, redox balance and nonspecific immune responses in Nile tilapia fingerlings. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs), professional antigen-presenting cells that process and deliver antigens using MHC II/I molecules, can be enhanced in numerous ways. Exosomes derived from heat‐ shocked tumor cells (HS‐TEXs) contain high amounts of heat-shock proteins (HSPs). HSPs, as chaperons, can induce DC maturation. This study aimed to investigate whether HS‐TEXs can promote DC maturation. To generate DC, bone marrow-derived cells were treated with Interleukin-4 and GM-CSF. Exosomes were isolated from heat-treated CT-26 cells. The expression level of HSP in exosomes was checked by western blot and the increase in the expression of this protein was observed. Then, HS‐TEXs were co-cultured with iDCs to determine DC maturity, and then DCs were co-cultured with lymphocytes to determine DC activity. Our results showed that DCs treated with HS‐TEXs express high levels of molecules involved in DC maturation and function including MHCII, CD40, CD83, and CD86. HS‐TEXs caused phenotypic and functional maturation of DCs. In addition, flow cytometric results reflected a higher proliferative response of lymphocytes in the iDC / Tex + HSP group. HS‐TEXs could be used as a strategy to improve DC maturation and activation. [ABSTRACT FROM AUTHOR]

Hair loss is one of the most common and distressing conditions that can be traumatic for an individual. Many non-pharmacological and pharmacological treatments for hair loss have been developed. However, serious side effects or limitations in terms of the hair regeneration potential still exist. One of the non-pharmacological treatments, biophysical stimulation, has shown promise in hair regeneration. Nevertheless, the associated discomfort and the need for external components such as an electrical power supply pose challenges to its widespread use. In this study, we present an innovative cationic fabric that utilizes repeatable asymmetrical ionic flow of a physiological fluid to internally stimulate hair follicles and skin. Characterization, ultrasonic, biochemical, and histological experiments were conducted. The use of this developed treatment significantly increased expressions of heat shock proteins and potentially improved immunoregulation in the skin, as well as increased the number of hair follicles in skin defect animals, with no adverse risks. [ABSTRACT FROM AUTHOR]

Simple Summary: A. m. jemenetica occurs naturally on the Arabian Peninsula and in tropical Africa, and this honeybee subspecies has acquired several morphological, behavioral and molecular adaptations to extreme summer temperatures in Saudi Arabia. In this study, expression levels of different heat-shock protein (hsp) genes in forager A. m. jemenetica (a thermotolerant honeybee subspecies) and A. m. carnica (a thermosusceptible subspecies) were explored and compared under desert and semi-arid climates within Saudi Arabia. The results revealed higher expression levels of hsp mRNAs in A. m. jemenetica compared to A. m. carnica. The expression levels of small- as well as large-molecular-weight heat-shock proteins were higher under desert climate conditions in the Riyadh region compared to the semi-arid conditions in Baha. It is clear that the expression of heat-shock proteins is a key molecular mechanism of A. m. jemenetica adaptation to extreme summer conditions. A. m. jemenetica is the indigenous honeybee of the Arabian Peninsula. It is highly adapted to extreme temperatures exceeding 40 °C, yet important molecular aspects of its adaptation are not well documented. In this study we quantify relative expression levels of small- and large-molecular-weight heat-shock proteins (hsp10, hsp28, hsp70, hsp83, hsp90 and hsc70 (mRNAs)) in the thermos-tolerant A. m. jemenetica and thermosusceptible A. m. carnica forager honeybee subspecies under desert (Riyadh) and semi-arid (Baha) summer conditions. The results showed significant day-long higher expression levels of hsp mRNAs in A. m. jemenetica compared to A. m. carnica under the same conditions. In Baha, the expression levels were very modest in both subspecies compared those in Riyadh though the expression levels were higher in A. m. jemenetica. The results also revealed a significant interaction between subspecies, which indicated milder stress conditions in Baha. In conclusion, the higher expression levels of hsp10, hsp28, hsp70ab, hsp83 and hsp90 mRNAs in A. m. jemenetica are key elements in the adaptive nature of A. m. jemenetica to local conditions that enhance its survival and fitness in high summer temperatures. [ABSTRACT FROM AUTHOR]

Simple Summary: Heat-shock proteins (HSPs) are molecular chaperones overexpressed in tumor cells and are necessary for their survival. In leukemia and lymphoma, HSPs have been reported to have unique cytoprotective effects on different cell death and growth pathways. In this review, we describe the implication of HSPs in those pathways in hematological malignancies and discuss the pertinence of detecting and targeting them for future innovative treatment strategies. Heat-shock proteins (HSPs) are powerful chaperones that provide support for cellular functions under stress conditions but also for the homeostasis of basic cellular machinery. All cancer cells strongly rely on HSPs, as they must continuously adapt to internal but also microenvironmental stresses to survive. In solid tumors, HSPs have been described as helping to correct the folding of misfolded proteins, sustain oncogenic pathways, and prevent apoptosis. Leukemias and lymphomas also overexpress HSPs, which are frequently associated with resistance to therapy. HSPs have therefore been proposed as new therapeutic targets. Given the specific biology of hematological malignancies, it is essential to revise their role in this field, providing a more adaptable and comprehensive picture that would help design future clinical trials. To that end, this review will describe the different pathways and functions regulated by HSP27, HSP70, HSP90, and, not least, HSP110 in leukemias and lymphomas. [ABSTRACT FROM AUTHOR]

Background: αB-Crystallin is a heat shock chaperone protein which binds to misfolded proteins to prevent their aggregation. It is overexpressed in a wide-variety of cancers. Previous studies using human cancer cell lines and human xenograft models have suggested potential tumor promoter (oncogene) roles for αB-Crystallin in a wide-spectrum of cancers. Methods: To determine the causal relationship between CRYAB overexpression and cancer, we generated a Cryab overexpression knock-in mouse model and monitor them for development of spontaneous and carcinogen (DMBA)-induced tumorigenesis. In order to investigate the mechanism of malignancies observed in this model multiple techniques were used such as immunohistochemical characterizations of tumors, bioinformatics analysis of publically available human tumor datasets, and generation of mouse embryonic fibroblasts (MEFs) for in vitro assays (clonogenic survival and migration assays and proteome analysis by mass-spectrometry). Results: This model revealed that constitutive overexpression of Cryab results in the formation of a variety of lethal spontaneous primary and metastatic tumors in mice. In vivo, the overexpression of Cryab correlated with the upregulation of epithelial-to-mesenchymal (EMT) markers, angiogenesis and some oncogenic proteins including Basigin. In vitro, using E1A/Ras transformed MEFs, we observed that the overexpression of Cryab led to the promotion of cell survival via upregulation of Akt signaling and downregulation of pro-apoptotic pathway mediator JNK, with subsequent attenuation of apoptosis as assessed by cleaved caspase-3 and Annexin V staining. Conclusions: Overall, through the generation and characterization of Cryab overexpression model, we provide evidence supporting the role of αB-Crystallin as an oncogene, where its upregulation is sufficient to induce tumors, promote cell survival and inhibit apoptosis. [ABSTRACT FROM AUTHOR]

The use of Clostridium butyricum in crustacean aquaculture for anti-abiotic stress is yet unknown. Feeds were formulated containing 0, 125, 250, 500, and 1000 mg/kg Clostridium butyricum (2 × 107 CFU/g), respectively. The giant freshwater prawns (Macrobrachium rosenbergii) were fed for 8 weeks in triplicate. The results showed that C. butyricum- supplemented groups improved growth performance significantly with the optimum level at 610 mg/kg. Ammonia stress reduced hemolymph glucose, total protein, total cholesterol, and triglyceride concentrations while dietary C. butyricum significantly increased hemolymph glucose and total protein levels after the ammonia challenge. Ammonia stress increased inducible nitric oxide synthase (iNOS) and nitric oxide (NO) levels, and the treatments supplemented with C. butyricum had considerably enhanced levels of iNOS and NO after stress. Treatment with C. butyricum increased the level of superoxide dismutase (SOD), and decreased the level of malondialdehyde (MDA) and superoxide anion, with the 125 mg/kg treated groups having the extreme value. Furthermore, C. butyricum -treated groups reduced the expression of HSPs after ammonia stress while the ammonia stress induced the expression of HSP60, HSP70, and HSP90. Dietary C. butyricum elevated the expression of peroxiredoxin-5 and toll in response to ammonia stress. The results indicate that dietary supplementation with 125–500 mg/kg of C. butyricum (2 × 107 CFU/g) improved biochemical and antioxidant features as well as intestinal immunity of M. rosenbergii under ammonia challenge by activating the toll signal pathway. • The optimum level of dietary C. butyricum is 615 mg/kg in M. rosenbergii. • Dietary C. butyricum improves the resistance to ammonia stress of M. rosenbergii. • C. butyricum relieves ammonia-induced intestinal oxidative stress of M. rosenbergii. • Heat-shock proteins and toll pathway partly control the intestinal oxidative stress. [ABSTRACT FROM AUTHOR]

Several stress‐activated signals are highly responsible for the thermal tolerance and attribute to the poor therapeutic outcome of photothermal therapy (PTT). In this study, the naturally human hair‐derived nanoparticles (Hair NPs) with significant photothermal conversion efficacy are explored to combine with stress‐activated signal inhibitors for maximizing the PTT efficiency. During the Hair NPs‐based PTT, two distinct signals are found to be remarkably upregulated. One is the heat‐induced overexpression of HSP90, and the other one is the activation of mitogen‐activated protein kinase (MAPK) signaling pathway. Through the integration of particular inhibitors (17‐allylamino‐17‐demethoxygeldanamycin (17AAG) specifically binding to HSP90 or LY2228820 targeting to p38 MAPK) and the subsequent modification of hyaluronic acid (HA), the resultant Hair NPs‐HA@inhibitor can specifically deliver the inhibitor into tumor cells with minimal side effects on normal tissues, which can specifically block the stressfully activated signals as well as inhibit the expression of their downstream effectors (e.g., MMPs, VEGF) that are closely related with tumor survival and invasion. Without these elements to protect tumor cells or promote tumor progression, the Hair NPs‐induced PTT effect can be much elevated, resulting in a superior antitumor efficacy. These findings represent an effective approach in maximizing PTT effect for fighting against tumor. [ABSTRACT FROM AUTHOR]

Even though anti-tuberculosis (TB) treatment is readily available, Mycobacterium tuberculosis (Mtb) infection continues to be a global threat with a high death rate recorded from a single infectious agent. This highlights the significance of developing new strategies to curb the growing Mtb infection cases. Host-directed therapies (HDT) offer a promising approach that includes both drug discovery and drug repurposing, aimed at identifying host targets and promoting immune cell populations that can lead to better infection outcomes. In this context, we investigated the potential of exogenous Binding Immunoglobulin Protein (BiP) to induce such changes ex-vivo using PBMCs from healthy (QFN-) and Mtb exposed (QFN+) individuals. We analysed cell surface expression and cytokine profiles across eight different stimulation conditions including human full-length BiP protein (20 μg/ml), TLR-9a (0.5 μM), BiP/TLR-9a combination, isoniazid (1 μM), H37Rv (MOI: 1: 10), and pooled bronchoalveolar lavage (BAL) samples collected at TB diagnosis (TBdx) and at month 6 (M6) of anti-TB treatment. Our results revealed that BiP-stimulated PBMCs showed a significant reduction of interleukin (IL)-10 secretion, along with increased IL-4, IL-5, IL-13, and soluble Fas-L (sFasL) secretion. We also observed that BiP stimulation enhanced the expression of membrane bound Fas-L (CD178) and IL5Ra (CD125) in B-cells isolated from both QFN- and QFN+ groups. Additionally, BiP exhibited a synergistic effect with TLR-9a, further boosting this co-expression. Moreover, we observed that BiP induced IL5Ra expression in both CD3+CD5lo and CD3+CD5hi T-cell populations. This study explores the effects of exogenous BiP on cell functionality and provides valuable insights into its potential to modulate host cell responses, which could be explored as a host-directed therapy for TB in the future. • Mycobacterium tuberculosis infection continues to be a global threat. • Host-directed therapy approach provides a platform to enhance immune responses. • QFN positive individuals shows an increased pro-inflammatory cytokine response. • Extracellular BiP increases the regulatory phenotype in B-cells in-vitro. • BiP and TLR-9a synergistically increases the anti-inflammatory cytokines in-vitro. [ABSTRACT FROM AUTHOR]

The glucocorticoid receptor (GR) at the blood–brain barrier (BBB) is involved in the pathogenesis of drug-resistant epilepsy with focal cortical dysplasia (FCD); however, the roles of GR isoforms GRα and GRβ in the dysplastic brain have not been revealed. We utilized dysplastic/epileptic and non-dysplastic brain tissue from patients who underwent resective epilepsy surgery to identify the GRα and GRβ levels, subcellular localization, and cellular specificity. BBB endothelial cells isolated from the dysplastic brain tissue (EPI-ECs) were used to decipher the key BBB proteins related to drug regulation and BBB integrity compared to control and transfected GRβ-overexpressed BBB endothelial cells. GRβ was upregulated in dysplastic compared to non-dysplastic tissues, and an imbalance of the GRα/GRβ ratio was significant in females vs. males and in patients > 45 years old. In EPI-ECs, the subcellular localization and expression patterns of GRβ, Hsp90, CYP3A4, and CYP2C9 were consistent with GRβ+ brain endothelial cells. Active matrix metalloproteinase levels and activity increased, whereas claudin-5 levels decreased in both EPI-ECs and GRβ+ endothelial cells. In conclusion, the GRβ has a major effect on dysplastic BBB functional proteins and is age and gender-dependent, suggesting a critical role of brain GRβ in dysplasia as a potential biomarker and therapeutic target in epilepsy. [ABSTRACT FROM AUTHOR]

This study aims to evaluate significant gene expression in severe hypoxic ischemic encephalopathy (HIE) in newborns, which can be used as a predictable measure for high-risk HIE infants. The study prospectively recruited 77 inborn near-term or term HIE newborns between January 2018 and December 2020. We measured six different genes within 6 h of life among the HIE infants and compared the gene levels between the mild- and severe-HIE groups. Among these, 64 HIE infants (83.1%) did not receive therapeutic hypothermia (TH) because they were categorized as mild HIE, and the 13 remaining (16.9%) infants were categorized as ≥ moderate-HIE group and received TH. More abnormal MRI findings, seizure, and use of anti-convulsant were more found in the ≥ moderate = HIE group along with longer mechanical ventilation days and hospitalization. Heat-shock protein 70 family 1 A (HSPA1A) and serpin family H member 1 (SERPINH1) genes, which encode heat-shock protein (HSP) 70 and 47, respectively, were significantly elevated in the ≥ moderate-HIE, seizure, and abnormal MRI groups. HSP 70 and 47 were significantly elevated in the severe-HIE group, possibly playing protective roles in inhibiting exacerbated neuroinflammation and maintaining a cellular homeostasis. At 18–24 months, ≥ moderate-HIE group manifested a significant language delay. [ABSTRACT FROM AUTHOR]

Steroid receptors form soluble heterocomplexes with the 90-kDa heat-shock protein (Hsp90) and other chaperones and co-chaperones. The assembly and composition of the oligomer is influenced by the presence and nature of the bound steroid. Although these receptors shuttle dynamically in and out of the nucleus, their primary localization in the absence of steroid can be mainly cytoplasmic, mainly nuclear, or partitioned into both cellular compartments. Upon steroid binding, receptors become localized to the nucleus via the transportosome, a retrotransport molecular machinery that comprises Hsp90, a high-molecular-weight immunophilin, and dynein motors. This molecular machinery, first evidenced in steroid receptors, can also be used by other soluble proteins. In this review, we dissect the complete model of this transport machinery system. The cytoplasmic movement of soluble proteins, such as steroid receptors, transcription factors, enzymes, and viral proteins, can be mediated by the transportosome, a molecular assembly that includes the chaperone Hsp90, a TPR-domain immunophilin, and dynein/dynactin motor proteins. In physiological conditions, the mature Hsp90-based heterocomplexes with client proteins show one TPR acceptor site, which creates a mutually excluded mechanism of TPR proteins for its occupancy. The relative abundance of each class of TPR-domain immunophilin determines the composition of the heterocomplex with the client factor and, consequently, its biological properties. Such a differential composition of the heterocomplex for a given client factor according to cell type may explain the pleiotropic effects observed for the same stimulus in cases such as the glucocorticoid receptor or NF-κB. [ABSTRACT FROM AUTHOR]

Protein misfolding is a major driver of ageing‐associated frailty and disease pathology. Although all cells possess multiple, well‐characterised protein quality control systems to mitigate the toxicity of misfolded proteins, how they are integrated to maintain protein homeostasis ('proteostasis') in health—and how their disintegration contributes to disease—is still an exciting and fast‐paced area of research. Under physiological conditions, the predominant route for misfolded protein clearance involves ubiquitylation and proteasome‐mediated degradation. When the capacity of this route is overwhelmed—as happens during conditions of acute environmental stress, or chronic ageing‐related decline—alternative routes for protein quality control are activated. In this review, we summarise our current understanding of how proteasome‐targeted misfolded proteins are retrafficked to alternative protein quality control routes such as juxta‐nuclear sequestration and selective autophagy when the ubiquitin–proteasome system is compromised. We also discuss the molecular determinants of these alternative protein quality control systems, attempt to clarify distinctions between various cytoplasmic spatial quality control inclusion bodies (e.g., Q‐bodies, p62 bodies, JUNQ, aggresomes, and aggresome‐like induced structures 'ALIS'), and speculate on emerging concepts in the field that we hope will spur future research—with the potential to benefit the rational development of healthy ageing strategies. [ABSTRACT FROM AUTHOR]

Climate change causes increased tree mortality leading to canopy loss and thus sun‐exposed forest floors. Sun exposure creates extreme temperatures and radiation, with potentially more drastic effects on forest organisms than the current increase in mean temperature. Such conditions might potentially negatively affect the maturation of mushrooms of forest fungi. A failure of reaching maturation would mean no sexual spore release and, thus, entail a loss of genetic diversity. However, we currently have a limited understanding of the quality and quantity of mushroom‐specific molecular responses caused by sun exposure. Thus, to understand the short‐term responses toward enhanced sun exposure, we exposed mushrooms of the wood‐inhabiting forest species Lentinula edodes, while still attached to their mycelium and substrate, to artificial solar light (ca. 30°C and 100,000 lux) for 5, 30, and 60 min. We found significant differentially expressed genes at 30 and 60 min. Eukaryotic Orthologous Groups (KOG) class enrichment pointed to defense mechanisms. The 20 most significant differentially expressed genes showed the expression of heat‐shock proteins, an important family of proteins under heat stress. Although preliminary, our results suggest mushroom‐specific molecular responses to tolerate enhanced sun exposure as expected under climate change. Whether mushroom‐specific molecular responses are able to maintain fungal fitness under opening forest canopies remains to be tested. [ABSTRACT FROM AUTHOR]

Gas plasma is a partially ionized gas increasingly recognized for targeting cancer. Several hypotheses attempt to explain the link between plasma treatment and cytotoxicity in cancer cells, all focusing on cellular membranes that are the first to be exposed to plasma-generated reactive oxygen species (ROS). One proposes high levels of aquaporins, membrane transporters of water and hydrogen peroxide, to mark tumor cell line sensitivity to plasma treatment. A second focuses on membrane-expression of redox-related enzymes such as NADPH oxidases (NOX) that may modify or amplify the effects of plasma-derived ROS, fueling plasma-induced cancer cell death. Another hypothesis is that the decreased cholesterol content of tumor cell membranes sensitizes these to plasma-mediated oxidation and subsequently, cytotoxicity. Screening 33 surface molecules in 36 tumor cell lines in correlation to their sensitivity to plasma treatment, the expression of aquaporins or NOX members could not explain the sensitivity but were rather associated with treatment resistance. Correlation with transporter or enzyme activity was not tested. Analysis of cholesterol content confirmed the proposed positive correlation with treatment resistance. Strikingly, the strongest correlation was found for baseline metabolic activity (Spearman r = 0.76). Altogether, these data suggest tumor cell metabolism as a novel testable hypothesis to explain cancer cell resistance to gas plasma treatment for further elucidating this innovative field's chances and limitations in oncology. [Display omitted] • Using a 33 surface marker screening in 38 human cell lines, three major hypothesis were tested on gas plasma cancer treatment. • Expression of aquaporins and redox-related enzymes correlated with plasma treatment resistance in cancer cells. • Basal metabolic activity showed the best correlation to gas plasma treatment resistance in tumor cells. [ABSTRACT FROM AUTHOR]

Iron is an essential micronutrient for most organisms and fungi are no exception. Iron uptake by fungi is facilitated by receptor-mediated internalization of siderophores, heme and reductive iron assimilation (RIA). The RIA employs three protein groups: (i) the ferric reductases (Fre5 proteins), (ii) the multicopper ferroxidases (Fet3) and (iii) the high-affinity iron permeases (Ftr1). Phenotyping under different iron concentrations revealed detrimental effects on spore swelling and hyphal formation under iron depletion, but yeast-like morphology under iron excess. Since access to iron is limited during pathogenesis, pathogens are placed under stress due to nutrient limitations. To combat this, gene duplication and differential gene expression of key iron uptake genes are utilized to acquire iron against the deleterious effects of iron depletion. In the genome of the human pathogenic fungus L. corymbifera, three, four and three copies were identified for FRE5, FTR1 and FET3 genes, respectively. As in other fungi, FET3 and FTR1 are syntenic and co-expressed in L. corymbifera. Expression of FRE5, FTR1 and FET3 genes is highly up-regulated during iron limitation (Fe-), but lower during iron excess (Fe+). Fe- dependent upregulation of gene expression takes place in LcFRE5 II and III, LcFTR1 I and II, as well as LcFET3 I and II suggesting a functional role in pathogenesis. The syntenic LcFTR1 I–LcFET3 I gene pair is co-expressed during germination, whereas LcFTR1 IILcFET3 II is co-expressed during hyphal proliferation. LcFTR1 I, II and IV were overexpressed in Saccharomyces cerevisiae to represent high and moderate expression of intracellular transport of Fe3+, respectively. Challenge of macrophages with the yeast mutants revealed no obvious role for LcFTR1 I, but possible functions of LcFTR1 II and IVs in recognition by macrophages. RIA expression pattern was used for a new model of interaction between L. corymbifera and macrophages. [ABSTRACT FROM AUTHOR]

Yellowhorn (Xanthoceras sorbifolium Bunge) is a woody oil species that is widely distributed in northwestern China. To investigate the molecular mechanisms underlying the drought and heat tolerance response of yellowhorn seedlings, changes in protein abundance were analyzed via comparative proteomics. Drought and heat treatment of seedlings was applied in growth chamber, and the leaves were harvested after 7 days of treatment. The total protein was extracted, and comparative proteomic analysis was performed via isobaric tag for relative and absolute quantitation (iTRAQ). The abundance of most of the proteins associated with oxidative phosphorylation, NADH dehydrogenase and superoxide dismutase (SOD) was reduced. The differential proteins associated with photosynthesis enzymes indicated that stress had different effects on photosystem I (PSI) and photosystem II (PSII). After comprehensively analyzing the results, we speculated that drought and heat stress could hinder the synthesis of riboflavin, reducing NADH dehydrogenase content, which might further have an impact on energy utilization. Yellowhorn seedlings relied on Fe–Mn SOD enzymes rather than Cu/Zn SOD enzymes to remove reactive oxygen species (ROS). In addition, heat-shock proteins (HSPs) had significant increase and played a key role in stress response, which could be divided into two categories according to their transcription and translation efficiency. Over all, the results can provide a basis for understanding the molecular mechanism underlying resistance to drought and heat stress in yellowhorn and for subsequent research of posttranslational modification-related omics of key proteins. • Yellowhorn relied on Fe–Mn SOD rather than Cu/Zn SOD to remove ROS under drought heat stress. • Drought heat stress hindered riboflavin synthesis, reduced NADH dehydrogenase content, further influenced energy utilization. • Drought and heat stress had different effects on photosystem I (PSI) and photosystem II (PSII). • The transcription and translation efficiency of different heat shock proteins were different. [ABSTRACT FROM AUTHOR]

Background: Heat-shock protein B1 (HSPB1) is among the most well-known and versatile member of the evolutionarily conserved family of small heat-shock proteins. It has been implicated to serve a neuroprotective role against various neurological disorders via its modulatory activity on inflammation, yet its exact role in neuroinflammation is poorly understood. In order to shed light on the exact mechanism of inflammation modulation by HSPB1, we investigated the effect of HSPB1 on neuroinflammatory processes in an in vivo and in vitro model of acute brain injury.Methods: In this study, we used a transgenic mouse strain overexpressing the human HSPB1 protein. In the in vivo experiments, 7-day-old transgenic and wild-type mice were treated with ethanol. Apoptotic cells were detected using TUNEL assay. The mRNA and protein levels of cytokines and glial cell markers were examined using RT-PCR and immunohistochemistry in the brain. We also established primary neuronal, astrocyte, and microglial cultures which were subjected to cytokine and ethanol treatments. TNFα and hHSPB1 levels were measured from the supernates by ELISA, and intracellular hHSPB1 expression was analyzed using fluorescent immunohistochemistry.Results: Following ethanol treatment, the brains of hHSPB1-overexpressing mice showed a significantly higher mRNA level of pro-inflammatory cytokines (Tnf, Il1b), microglia (Cd68, Arg1), and astrocyte (Gfap) markers compared to wild-type brains. Microglial activation, and 1 week later, reactive astrogliosis was higher in certain brain areas of ethanol-treated transgenic mice compared to those of wild-types. Despite the remarkably high expression of pro-apoptotic Tnf, hHSPB1-overexpressing mice did not exhibit higher level of apoptosis. Our data suggest that intracellular hHSPB1, showing the highest level in primary astrocytes, was responsible for the inflammation-regulating effects. Microglia cells were the main source of TNFα in our model. Microglia isolated from hHSPB1-overexpressing mice showed a significantly higher release of TNFα compared to wild-type cells under inflammatory conditions.Conclusions: Our work provides novel in vivo evidence that hHSPB1 overexpression has a regulating effect on acute neuroinflammation by intensifying the expression of pro-inflammatory cytokines and enhancing glial cell activation, but not increasing neuronal apoptosis. These results suggest that hHSPB1 may play a complex role in the modulation of the ethanol-induced neuroinflammatory response. [ABSTRACT FROM AUTHOR]

We analyzed possible molecular mechanisms of central serotonergic trophic support of the retina and pathogenesis of retinitis pigmentosa (RP) in an experimental model on rabbits and in patients diagnosed with this pathology. Grave-degree experimental RP was induced in male rabbits through i.v. administration of monoiodoacetic acid (MIAA, 26 mg/kg body mass). With application of an indirect ELISA test, the levels of heat shock protein 70 kDa (HSP70) and rhodopsin in the retina and those of natural anti-SMAP autoantibodies in blood serum of the patients were measured. Serotoninmodulating anticonsolidation protein (SMAP, [5]) and anti-SMAP antibodies were administered to the animals with RP. Significant downregulation of the ERG amplitude elicited by light flashes of different intensities (P < 0.001), downregulation of the rhodopsin content (P < 0.001), and upregulation of HSP70 content (P < 0.001) in the retina of MIAA-administered rabbits were observed. Intravitreal injections of SMAP and anti-SMAP antibodies to MIAA-administered rabbits resulted in significant upregulation of the rhodopsin (P < 0.001) and HSP70 (P < 0.001) contents in the retina. Downregulation of titers of natural autoimmune anti-SMAP antibodies in blood serum of the RP-diagnosed patients relative to those in healthy persons of the same age (P < 0.01) was seen. Molecular mechanisms underlying the hypothalamic serotonergic trophic regulatory effects on retinal receptor cells through retrograde and anterograde axonal transports are discussed. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) is the most prevalent type of cancer in men worldwide. In Saudi Arabia, the rate of PC is increasing annually. The sex steroid hormones androgens and their receptors have critical roles in PC development and progression. Additionally, apoptosis-related proteins such as heat-shock proteins are vital molecules in PC development. Steroid hormone-deprivation therapies remain the essential treatment for patients with metastatic PCs; however, acquired resistance to hormone deprivation and the transition to PC androgen independence is a major health obstacle. In this review, we aim to detail the roles of androgens, androgen receptors and sex steroid hormones in inducing apoptosis in PC. [ABSTRACT FROM AUTHOR]

Background: The blood-feeding behavior evolved multiple times in Insecta lineages and it represents an excellent opportunity to study patterns of convergent molecular evolution regarding this habit. In insects the expansion of some gene families is linked with blood-feeding behavior, but a wide study comparing the evolution of these gene families among different lineages is still missing. Here we gathered genomic data from six independently-evolved hematophagous lineages, aiming to identify convergent expansions and/or contractions of gene families in hematophagous lineages of insects. Results: We found four rapidly evolving gene families shared by at least two hematophagous independently-evolved lineages, including a heat-shock and a chemosensory protein. On the expression of these four rapidly evolving gene families we found more genes expressed in mated individuals compared with virgin individuals in rapidly-expanded families and more genes expressed in non-blood-feeding individuals compared with blood-feeding individuals in rapidly-contracted families. Conclusion: Our results reveal a new set of candidate genes to be explored in further analysis to help the development of new strategies to deal with blood-feeding vectors and also presents a new perspective to study the evolution of hematophagy identifying convergent molecular patterns. [ABSTRACT FROM AUTHOR]

The Van fish are a cyprinid species endemic to Turkey's largest soda lake, Lake Van, and have great economic value because they are a food source. Once a year, the fish take part in reproductive migration to the fresh waters flowing into the lake. The fish migrate from an extreme environment with high salinity (2.2%) and high pH (9.8). These fish are unable to reproduce in this alkaline environment and must migrate to fresh water during their breeding season. The aim of the present study is to report the presence of the myxosporean parasites on the gills and the pathological changes. Changes in gill histopathology, mucocytes, mitochondria-rich cells, expression of Heat Shock Protein 70 (Hsp70), and ATPase (NKA) were observed in the gill tissue. As a result of the histopathological changes in gills, infected fish had abundant plasmodia with different sizes. Plasmodia were found on gill filaments inside white ovoid-shaped structures. It was observed that plasmodia were contained on the primary filament which changed the histological structure of the gill tissue to a large extent. It was determined that the density and size of mucocytes in the infected areas of the gill tissue increased, whereas the number of mitochondria-rich cells decreased. Hsp70, an indicator of stress, was not different between normal and infected fish. [ABSTRACT FROM AUTHOR]

The negative effects of the current agricultural practices include erosion, acidification, loss of soil organic matter (dehumification), loss of soil structure, soil contamination by risky elements, reduction of biological diversity and land use for non-agricultural purposes. All these effects are a huge risk to the further development of soil quality from an agronomic point of view and its resilience to projected climate change. Organic matter has a crucial role in it. Relatively significant correlations with the quality or the health of soil parameters and the soil organic matter or some fraction of the soil organic matter have been found. In particular, Ctot, Cox, humic and fulvic acids, the C/N ratio, and glomalin. Our work was focused on glomalin, a glycoprotein produced by the hyphae and spores of arbuscular mycorrhizal fungi (AMF), which we classify as Glomeromycota. Arbuscular mycorrhiza, and its molecular pathways, is not a well understood phenomenon. It appears that many proteins are involved in the arbuscular mycorrhiza from which glomalin is probably one of the most significant. This protein is also responsible for the unique chemical and physical properties of soils and has an ecological and economical relevance in this sense and it is a real product of the mycorrhiza. Glomalin is very resistant to destruction (recalcitrant) and difficult to dissolve in water. Its extraction requires specific conditions: high temperature (121°C) and a citrate buffer with a neutral or alkaline pH. Due to these properties, glomalin (or its fractions) are very stable compounds that protect the soil aggregate surface. In this review, the actual literature has been researched and the importance of glomalin is discussed. [ABSTRACT FROM AUTHOR]

A photothermal bacterium (PTB) is reported for tumor‐targeted photothermal therapy (PTT) by using facultative anaerobic bacterium Shewanella oneidensis MR‐1 (S. oneidensis MR‐1) to biomineralize palladium nanoparticles (Pd NPs) on its surface without affecting bacterial activity. It is found that PTB possesses superior photothermal property in near infrared (NIR) regions, as well as preferential tumor‐targeting capacity. Zeolitic imidazole frameworks‐90 (ZIF‐90) encapsulating photosensitizer methylene blue (MB) are hybridized on the surface of living PTB to further enhance PTT efficacy. MB‐encapsulated ZIF‐90 (ZIF‐90/MB) can selectively release MB at mitochondria and cause mitochondrial dysfunction by producing singlet oxygen (1O2) under light illumination. Mitochondrial dysfunction further contributes to adenosine triphosphate (ATP) synthesis inhibition and heat shock proteins (HSPs) down‐regulated expression. The PTB‐based therapeutic platform of PTB@ZIF‐90/MB demonstrated here will find great potential to overcome the challenges of tumor targeting and tumor heat tolerance in PTT. [ABSTRACT FROM AUTHOR]

The negative effects of the current agricultural practices include erosion, acidification, loss of soil organic matter (dehumification), loss of soil structure, soil contamination by risky elements, reduction of biological diversity and land use for non-agricultural purposes. All these effects are a huge risk to the further development of soil quality from an agronomic point of view and its resilience to projected climate change. Organic matter has a crucial role in it. Relatively significant correlations with the quality or the health of soil parameters and the soil organic matter or some fraction of the soil organic matter have been found. In particular, Ctot, Cox, humic and fulvic acids, the C/N ratio, and glomalin. Our work was focused on glomalin, a glycoprotein produced by the hyphae and spores of arbuscular mycorrhizal fungi (AMF), which we classify as Glomeromycota. Arbuscular mycorrhiza, and its molecular pathways, is not a well understood phenomenon. It appears that many proteins are involved in the arbuscular mycorrhiza from which glomalin is probably one of the most significant. This protein is also responsible for the unique chemical and physical properties of soils and has an ecological and economical relevance in this sense and it is a real product of the mycorrhiza. Glomalin is very resistant to destruction (recalcitrant) and difficult to dissolve in water. Its extraction requires specific conditions: high temperature (121°C) and a citrate buffer with a neutral or alkaline pH. Due to these properties, glomalin (or its fractions) are very stable compounds that protect the soil aggregate surface. In this review, the actual literature has been researched and the importance of glomalin is discussed. [ABSTRACT FROM AUTHOR]

Paracoccidioidomycosis (PCM) is a systemic mycosis autochthonous to Latin America and endemic to Brazil, which has the majority of the PCM cases. PCM is acquired through the inhalation of propagules of fungi from genus Paracoccidioides spp. and mainly affects the lungs. We have previously shown that P. brasiliensis -infected mice treated with single-dose of recombinant 60-kDa-heat shock protein from P. brasiliensis (rPbHsp60) had a worsening infection in comparison to animals only infected. In this study, we investigate whether the treatment of infected mice with PB_HSP60 gene cloned into a plasmid (pVAX1- PB_HSP60) would result in efficient immune response and better control of the disease. The harmful impact of single-dose therapy with protein was not seen with plasmid preparations. Most importantly, three doses of pVAX1- PB_HSP60 and protein induced a beneficial effect in experimental PCM with a reduction in fungal load and lung injury when compared with infected mice treated with pVAX1 or PBS. The increase of the cytokines IFN-γ, TNF, and IL-17 and the decrease of IL-10 observed after treatment with three doses of pVAX1- PB_HSP60 appears to be responsible for the control of infection. These results open perspectives of the therapeutic use of Hsp60 in PCM. [ABSTRACT FROM AUTHOR]

Abstract Heat-stress exposure increased the expression of heat-shock proteins (HSPs), B-cell lymphoma 2 (BCL-2) and anti-oxidative enzymes to maintain normal cellular function by attenuating the oxidative reaction and apoptosis. Reducing the stress response or enhancing anti-stress capability is an important goal in animal production. Our previous study indicated a protective role of flavangenol, a pine bark extract, in chicks after three hours of high-temperature exposure. However, the cellular mechanism of flavangenol was not clarified ex vivo. In the current study, we investigated the effect of flavangenol on cellular apoptosis and oxidation in heat-stressed treated chick brain cells (mixed neurons and glia cells). The primary brain cells were isolated from the diencephalon of 14-day-old chicks and cultured at 41.5 °C (to mimic the body temperature of young chicks), and were treated with flavangenol from day 3 of isolation to day 8. Cells were kept bathed in the cell culture dish under a high temperature (HT: 45 °C, 20 or 60 min) on day 8 and were then collected for analysis of cell viability as well as for HSP and other related gene expression. Flavangenol treatment significantly increased cell viability and BCL-2 mRNA expression, and attenuated HSP-70 and BCL-2-associated X protein mRNA expression. Moreover, flavangenol treatment elevated the mRNA expression of glutathione peroxidase in the HT group, which indicates that cellular anti-oxidative ability was strengthened by flavangenol. In conclusion, flavangenol may play a protective role in cells damaged or killed by heat stress by increasing cellular anti-oxidative pathways. Highlights • Flavangenol attenuated the mRNA expression of HSPs induced by heat stress. • Flavangenol increased the BCL-2 and GPX mRNA expression under heat stress. • Flavangenol have beneficial effect against heat stress induced cellular damage. • Flavangenol enhanced the cellular anti-oxidative ability. [ABSTRACT FROM AUTHOR]

Recently, we found that in ovo feeding of L-leucine (L-Leu) stimulated the metabolism of lipids and afforded thermotolerance in male Chunky broiler chicks. In this study, we investigated the effects of feeding L-Leu in ovo on the metabolism of amino acids and on the cellular stress response mainly in the central and peripheral tissues in neonatal male broiler chicks and partly in embryonic tissues. Chicks (9 d old) were exposed to high ambient temperature (HT : 35 ± 1°C) or control thermoneutral temperature (CT : 28 ± 1°C) for 180 min. The ambient temperatures were based on our recent reports and the recommendation of the Chunky broiler manual in which 28°C has been suggested as a normal ambient temperature for 5 to 9-d-old broiler chicks. In ovo feeding of L-Leu caused a significant (P < 0.05) decline in diencephalic arginine concentrations but it increased the diencephalic and plasma lysine concentrations when compared with the control chicks under HT. Notably, in ovo feeding of L-Leu significantly (P < 0.05) attenuated the increment of hepatic arginine compared with the control chicks under HT. Interestingly, in ovo feeding of L-Leu significantly (P < 0.05) attenuated the diencephalic gene expression of heat-shock protein (HSP) −70 and −90 in heat-exposed chicks. The gene expressions of mammalian target of rapamycin (mTOR) and its downstream genes (ribosomal protein S6 kinase (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1)) in the central and peripheral tissues were not influenced in the chicks under heat stress. We found that the gene expressions of mTOR, S6K1, and 4E-BP1 were significantly (P < 0.05) stimulated only in the embryonic breast muscle, and not in the other embryonic tissues, by in ovo feeding of L-Leu. In conclusion, in ovo feeding of L-Leu caused a change in the metabolism of amino acids in response to heat stress in broiler chicks. Attenuated gene expressions of HSP-70 and −90 under heat stress further suggests that in ovo feeding of L-Leu may afford thermotolerance in broilers. [ABSTRACT FROM AUTHOR]

Key message: OsHSP50.2, an HSP90 family gene up-regulated by heat and osmotic stress treatments, positively regulates drought stress tolerance probably by modulating ROS homeostasis and osmotic adjustment in rice.Abstract: Heat-shock proteins (HSPs) serve as molecular chaperones for a variety of client proteins in abiotic stress response and play pivotal roles in protecting plants against stress, but the molecular mechanism remains largely unknown. Here, we report an HSP90 family gene, OsHSP50.2, which acts as a positive regulator in drought stress tolerance in rice (Oryza sativa). OsHSP50.2 was ubiquitously expressed and its transcript level was up-regulated by heat and osmotic stress treatments. Overexpression of OsHSP50.2 in rice reduced water loss and enhanced the transgenic plant tolerance to drought and osmotic stresses. The OsHSP50.2-overexpressing plants exhibited significantly lower levels of electrolyte leakage and malondialdehyde (MDA) and less decrease of chlorophyll than wild-type plants under drought stress. Moreover, the OsHSP50.2-overexpressing plants had significantly higher SOD activity under drought stress compared with the wild type. These results imply that OsHSP50.2 positively regulates drought stress tolerance in rice, probably through the modulation of reactive oxygen species (ROS) homeostasis. Additionally, the OsHSP50.2-overexpressing plants accumulated significantly higher content of proline than the wild type under drought stress, which contributes to the improved protection ability from drought stress damage via osmotic adjustment. Our findings reveal that OsHSP50.2 plays a crucial role in drought stress response, and it may possess high potential usefulness in drought tolerance improvement of rice. [ABSTRACT FROM AUTHOR]

The production performance of livestock is influenced by short-term variation in weather pattern. Goat adapts to varied ecological conditions and maintains productivity; however, wide variation has been observed among individual animals in response to environmental stimuli in a population. The objective of the present study was to identify the contrasting phenotypes on the basis of the physiological response in goats during heat stress. The study utilised 138 Jamunapari and 242 Barbari goats during peak heat-stress period and 82 Jamunapari and Barbari goats under thermo-neutral conditions. The physiological response of goats to different environmental conditions was evaluated by recording various parameters such as rectal temperature (RT), respiration rate (RR) and heart rate (HR). The temperature humidity index varied from 85.36 to89.8G and from 65.32 to 73.12 during heat-stress and thermo-neutral assessments respectively. There was direct increase in HR and RR (≥25%) due to heat stress in the animals, as compared with those in thermo-neutral conditions. On the basis of the distribution of RR and HR values across the breed in the population, the individuals having a RR of ≥50 and a HR of ≥ 130 are recognised as heat stress-susceptible phenotypes and those having a RR of ≤30 and a HR of ≤100 are recognised as heat stress-tolerant individuals. Different biomarkers were analysed in plasma, while heat-shock proteins and leptin were analysed in tissue extracts by ELISA. C-reactive protein and HSP90 concentrations were significantly (P < 0.05) different between heat stress-susceptible and heat stress-tolerant individuals. Heat-shock proteins HSP70, HSP 90, and C-reactive protein and triiodothyronine were reliable indicators of long-term heat stress. Identification of contrasting phenotypes in regard to heat stress is necessary so as to evaluate the expression pattern at a cellular level, as well as physiological and biochemical parameters. [ABSTRACT FROM AUTHOR]

Molecular chaperones or heat shock proteins are a large protein family with important functions in every cellular organism. Among all types of the heat shock proteins, information on the ER-localized HSP90 protein (HSP90B) and its encoding gene is relatively scarce in the literature, especially in photosynthetic organisms. In this study, expression profiles as well as promoter sequence of the HSP90B gene were investigated in the model green alga Chlamydomonas reinhardtii . We have found that HSP90B is strongly induced by heat and ER stresses, while other short-term exposure to abiotic stresses, such as salinity, dark-to-light transition or light stress does not appear to affect the expression. Promoter truncation analysis as well as chromatin immunoprecipitation using the antibodies recognizing histone H3 and acetylated histone H3, revealed a putative core constitutive promoter sequence between −1 to −253 bp from the transcription start site. Our results also suggested that the nucleotides upstream of the core promoter may contain repressive elements such as putative repressor binding site(s). [ABSTRACT FROM AUTHOR]

Heat-shock proteins (HSPs), one of the evolutionarily conserved protein families, are widely found in various organisms, and play important physiological functions. Nevertheless, HSPs have not been systematically analyzed in esophageal squamous cell carcinoma (ESCC). In this study, we applied the protein-protein interaction (PPI) network methodology to explore the characteristics of HSPs, and integrate their expression in ESCC. First, differentially expressed HSPs in ESCC were identified from our previous RNA-seq data. By constructing a specific PPI network, we found differentially expressed HSPs interacted with hundreds of neighboring proteins. Subcellular localization analyses demonstrated that HSPs and their interacting proteins distributed in multiple layers, from membrane to nucleus. Functional enrichment annotation analyses revealed known and potential functions for HSPs. KEGG pathway analyses identified four significant enrichment pathways. Moreover, three HSPs (DNAJC5B, HSPA1B, and HSPH1) could serve as promising targets for prognostic prediction in ESCC, suggesting these HSPs might play a significant role in the development of ESCC. These multiple bioinformatics analyses have provided a comprehensive view of the roles of heat-shock proteins in esophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Molecular hydrogen exerts its effect on multiple pathologies, including oxidative stress, inflammation, and apoptosis. However, its molecular mechanisms have not been fully elucidated. In order to explore the effects of molecular hydrogen, we meta-analysed gene expression profiles modulated by molecular hydrogen. We performed microarray analysis of the mouse liver with or without drinking hydrogen water. We also integrated two previously reported microarray datasets of the rat liver into meta-analyses. We used two categories of meta-analysis methods: the cross-platform method and the conventional meta-analysis method (Fisher’s method). For each method, hydrogen-modulated pathways were analysed by (i) the hypergeometric test (HGT) in the class of over-representation analysis (ORA), (ii) the gene set enrichment analysis (GSEA) in the class of functional class scoring (FCS), and (iii) the signalling pathway impact analysis (SPIA), pathway regulation score (PRS), and others in the class of pathway topology-based approach (PTA). Pathways in the collagen biosynthesis and the heat-shock response were up-regulated according to (a) HGT with the cross-platform method, (b) GSEA with the cross-platform method, and (c) PRS with the cross-platform method. Pathways in cell cycles were down-regulated according to (a) HGT with the cross-platform method, (b) GSEA with the cross-platform method, and (d) GSEA with the conventional meta-analysis method. Because the heat-shock response leads to up-regulation of collagen biosynthesis and a transient arrest of cell cycles, induction of the heat-shock response is likely to be a primary event induced by molecular hydrogen in the liver of wild-type rodents. [ABSTRACT FROM AUTHOR]

The 'intermediate seed' category was defined in the early 1990s using coffee (Coffea arabica) as a model. In contrast to orthodox seeds, intermediate seeds cannot survive complete drying, which is a major constraint for seed storage and has implications for both biodiversity conservation and agricultural purposes. However, intermediate seeds are considerably more tolerant to drying than recalcitrant seeds, which are highly sensitive to desiccation. To gain insight into the mechanisms governing such differences, changes in desiccation tolerance (DT), hormone contents, and the transcriptome were analysed in developing coffee seeds. Acquisition of DT coincided with a dramatic transcriptional switch characterised by the repression of primary metabolism, photosynthesis, and respiration, and the up-regulation of genes coding for late-embryogenesis abundant (LEA) proteins, heat-shock proteins (HSPs), and antioxidant enzymes. Analysis of the heat-stable proteome in mature coffee seeds confirmed the accumulation of LEA proteins identified at the transcript level. Transcriptome analysis also suggested a major role for ABA and for the transcription factors CaHSFA9, CaDREB2G, CaANAC029, CaPLATZ, and CaDOG-like in DT acquisition. The ability of CaHSFA9 and CaDREB2G to trigger HSP gene transcription was validated by Agrobacterium-mediated transformation of coffee somatic embryos. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor deficits induced by dopaminergic neuronal death in the substantia nigra (SN). Finding a successful neuroprotective therapy is still challenging despite improved knowledge of the etiology of PD and a variety of medications intended to reduce symptoms. Lapatinib (LAP), an FDA-approved anti-cancer medication, has been stated to exert its effect through the modulation of oxidative stress. Furthermore, recent studies display the neuroprotective effects of LAP in epilepsy, encephalomyelitis, and Alzheimer's disease in rodent models through the modulation of oxidative stress and ferroptosis. Nevertheless, it is questionable whether LAP exerts neuroprotective effects in PD. In the current study, administration of 100 mg/kg LAP in rotenone-treated rats for 21 days ameliorates motor impairment, debilitated histopathological alterations, and revived dopaminergic neurons by increasing tyrosine hydroxylase (TH) expression in SN, along with increased dopamine level. LAP remarkably restored the antioxidant defense mechanism system, GPX4/GSH/NRF2 axis, inhibiting oxidative markers, including iron, TfR1, PTGS2, and 4-HNE, along with suppression of p-EGFR/c-SRC/PKCβII/PLC-γ/ACSL-4 pathway. Moreover, LAP modulates HSP90/CDC37 chaperone complex, regulating many key pathological markers of PD, including LRRK2, c-ABL, and α-syn. It is concluded that LAP has neuroprotective effects in PD via modulation of many key parameters implicated in PD pathogenesis. Taken together, the current study offers insights into the potential repositioning of LAP as a disease-modifying drug in PD. [Display omitted] • Lapatinib inhibits rotenone-induced parkinsonism in rats. • Lapatinib restores antioxidant NRF2/GPX4/GSH system. • HSP90/CDC37 controls parkinsonism by regulating many clients' functions and stability. • Lapatinib inhibits HSP90/CDC37 which regulates key factors in PD. • Lapatinib, an anti-cancer drug, may be a potential disease-modifying agent for PD. [ABSTRACT FROM AUTHOR]

Plants growing under field conditions are constantly exposed, either simultaneously or sequentially, to more than one abiotic stress factor. Plants have evolved sophisticated sensory systems to perceive a number of stress signals that allow them to activate the most adequate response to grow and survive in a given environment. Recently, cross-stress tolerance (i.e. tolerance to a second, strong stress after a different type of mild primary stress) has gained attention as a potential means of producing stress-resistant crops to aid with global food security. Heat or cold priming-induced cross-tolerance is very common in plants and often results from the synergistic co-activation of multiple stress signalling pathways, which involve reactive nitrogen species (RNS), reactive oxygen species (ROS), reactive carbonyl species (RCS), plant hormones and transcription factors. Recent studies have shown that the signalling functions of ROS, RNS and RCS, most particularly hydrogen peroxide, nitric oxide (NO) and methylglyoxal (MG), provide resistance to abiotic stresses and underpin cross-stress tolerance in plants by modulating the expression of genes as well as the post-translational modification of proteins. The current review highlights the key regulators and mechanisms underlying heat or cold priming-induced cross-stress tolerance in plants, with a focus on ROS, MG and NO signalling, as well as on the role of antioxidant and glyoxalase systems, osmolytes, heat-shock proteins (HSPs) and hormones. Our aim is also to provide a comprehensive idea on the topic for researchers using heat or cold priming-induced cross-tolerance as a mechanism to improve crop yields under multiple abiotic stresses. [ABSTRACT FROM AUTHOR]

Dysregulated microglial responses are central in neurodegenerative proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar disease (FTLD). Pathologic TDP-43, which is typically found in intracellular inclusions, is a misfolding protein with emerging roles in ALS and FTLD. Recently, TDP-43 species have been found in extracellular fluids of patients; however, the overall implications of TDP-43-mediated signaling linked to neuroinflammation are poorly understood. Our work--the first, to our knowledge, to focus on innate immunity responses to TDP-43 aggregates--shows that such species are internalized by microglia and cause abnormal mobilization of endogenous TDP-43. Exposure to TDP-43 aggregates elicited not only IL-1ß, but also NLRP3-dependent and noncanonical IL-18 processing. Moreover, we report a link between TDP-43 and neuronal loss via the apoptosis-independent emerging roles of caspase-3 in neurotoxic inflammation. Our results further support the view of noncell autonomous neurodegenerative mechanisms in ALS. Remarkably, we demonstrate that TDP-43 aggregates bind to and colocalize with MAPK/MAK/MRK overlapping kinase (MOK) and show that its phosphorylation status is disrupted. Finally, we show that this TDP-43-caused activation state can be altered by exogenous Hsp27 and Hsp70 chaperones. Our study provides new insight into the immune phenotype, mechanisms, and signaling pathways that operate in microglial neurotoxic activation in ALS. [ABSTRACT FROM AUTHOR]

Mitochondria Ca 2+ overload has long been recognized as a cell death trigger. Unexpectedly, we demonstrated a signaling complex composed of Calmodulin (CaM), Arabidopsis thaliana Bcl-2-associated athanogene 5 (AtBAG5) and Heat-shock cognate 70 protein (Hsc70) within Arabidopsis thaliana mitochondria which transduces mitochondria Ca 2+ elevations to suppress leaf senescence. Gain- and loss-of-function AtBAG5 mutant plants revealed that, mitochondria Ca 2+ elevation significantly increase chlorophyll retention and decrease H 2 O 2 level in dark-induced leaf senescence assay. Based on our findings, we proposed a molecular mechanism in which chronic mitochondria Ca 2+ elevation reduced ROS levels and thus inhibits leaf senescence. [ABSTRACT FROM AUTHOR]

Mechanistic trade-offs between traits under selection can shape and constrain evolutionary adaptation to environmental stressors. However, our knowledge of the quantitative and qualitative overlap in the molecular machinery among stress tolerance traits is highly restricted by the challenges of comparing and interpreting data between separate studies and laboratories, as well as to extrapolating between different levels of biological organization. We investigated the expression of the constitutive proteome (833 proteins) of 35 Drosophila melanogaster replicate populations artificially selected for increased resistance to six different environmental stressors. The evolved proteomes were significantly differentiated from replicated control lines. A targeted analysis of the constitutive proteomes revealed a regime-specific selection response among heat-shock proteins, which provides evidence that selection also adjusts the constitutive expression of these molecular chaperones. Although the selection response in some proteins was regime specific, the results were dominated by evidence for a 'common stress response.' With the exception of high temperature survival, we found no evidence for negative correlations between environmental stress resistance traits, meaning that evolutionary adaptation is not constrained by mechanistic trade-offs in regulation of functional important proteins. Instead, standing genetic variation and genetic trade-offs outside regulatory domains likely constrain the evolutionary responses in natural populations. [ABSTRACT FROM AUTHOR]

Hsp47, a collagen-specific molecular chaperone that localizes in the endoplasmic reticulum (ER), is indispensable for molecular maturation of collagen. Hsp47, which is encoded by the SERPINH1 gene, belongs to the serpin family and has the serpin fold; however, it has no serine protease inhibitory activity. Hsp47 transiently binds to procollagen in the ER, dissociates in the cis -Golgi or ER–Golgi intermediate compartment (ERGIC) in a pH-dependent manner, and is then transported back to the ER via its RDEL retention sequence. Hsp47 recognizes collagenous (Gly-Xaa-Arg) repeats on triple-helical procollagen and can prevent local unfolding and/or aggregate formation of procollagen. Gene disruption of Hsp47 in mice causes embryonic lethality due to impairments in basement membrane and collagen fibril formation. In Hsp47 -knockout cells, the type I collagen triple helix forms abnormally, resulting in thin and frequently branched fibrils. Secretion of type I collagens is slow and plausible in making aggregates of procollagens in the ER of hsp47-knocked out fibroblasts, which are ultimately degraded by autophagy. Mutations in Hsp47 are causally associated with osteogenesis imperfecta. Expression of Hsp47 is strongly correlated with expression of collagens in multiple types of cells and tissues. Therefore, Hsp47 represents a promising target for treatment of collagen-related disorders, including fibrosis of the liver, lung, and other organs. [ABSTRACT FROM AUTHOR]

We investigated the thermal effects of radiofrequency electromagnetic fields (RFEMFs) on the variation in core temperature and gene expression of some stress markers in rats. Sprague- Dawley rats were exposed to 2.14 GHz wideband code division multiple access (W-CDMA) RF signals at a whole-body averaged specific absorption rate (WBA-SAR) of 4 W/kg, which causes behavioral disruption in laboratory animals, and 0.4 W/kg, which is the limit for the occupational exposure set by the International Commission on Non-Ionizing Radiation Protection guideline. It is important to understand the possible in vivo effects derived from RF-EMF exposures at these intensities. Because of inadequate data on real-time core temperature analyses using free-moving animal and the association between stress and thermal effects of RF-EMF exposure, we analyzed the core body temperature under nonanesthetic condition during RF-EMF exposure. The results revealed that the core temperature increased by approximately 1.5°C compared with the baseline and reached a plateau till the end of RF-EMF exposure. Furthermore, we analyzed the gene expression of heat-shock proteins (Hsp) and heat-shock transcription factors (Hsf) family after RF-EMF exposure. At WBA-SAR of 4 W/kg, some Hsp and Hsf gene expression levels were significantly upregulated in the cerebral cortex and cerebellum following exposure for 6 hr/day but were not upregulated after exposure for 3 hr/day. On the other hand, there was no significant change in the core temperature and gene expression at WBA-SAR of 0.4 W/kg. Thus, 2.14-GHz RF-EMF exposure at WBA-SAR of 4 W/kg induced increases in the core temperature and upregulation of some stress markers, particularly in the cerebellum. [ABSTRACT FROM AUTHOR]

Trypanosome evolution was so far essentially studied on the basis of phylogenetic analyses of small subunit ribosomal RNA (SSU-rRNA) and glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) genes. We used for the first time the 70 kDa heat-shock protein gene ( hsp 70) to investigate the phylogenetic relationships among 11 Trypanosoma species on the basis of 1380 nucleotides from 76 sequences corresponding to 65 strains. We also constructed a phylogeny based on combined datasets of SSU-rDNA, gGAPDH and hsp 70 sequences. The obtained clusters can be correlated with the sections and subgenus classifications of mammal-infecting trypanosomes except for Trypanosoma theileri and Trypanosoma rangeli . Our analysis supports the classification of Trypanosoma species into clades rather than in sections and subgenera, some of which being polyphyletic. Nine clades were recognized: Trypanosoma carassi , Trypanosoma congolense , Trypanosoma cruzi , Trypanosoma grayi , Trypanosoma lewisi , T. rangeli , T. theileri , Trypanosoma vivax and Trypanozoon . These results are consistent with existing knowledge of the genus' phylogeny. Within the T. cruzi clade, three groups of T. cruzi discrete typing units could be clearly distinguished, corresponding to TcI, TcIII, and TcII + V + VI, while support for TcIV was lacking. Phylogenetic analyses based on hsp 70 demonstrated that this molecular marker can be applied for discriminating most of the Trypanosoma species and clades. [ABSTRACT FROM AUTHOR]

Accumulating evidence has established that periodontitis was an independent risk factor for coronary heart disease (CAD). Porphyromonus gingivalis (P. gingivalis), a major periodontal pathogen, has already been shown to have a significant role in the inflammatory response of CAD in vivo. The aim of the present study was to identify whether P. gingivalis heat-shock protein 60 (HSP60) induced the dysfunction of human umbilical vein endothelial cells (HUVECs) in vitro. HUVECs were stimulated with a range of P. gingivalis HSP60 concentrations (1, 10 and 100 ng/l) at different time-points. The levels of vascular endothelial (VE)-cadherin, endothelial nitric oxide synthase (eNOS) and cysteinyl aspartate-specific protease-3 (caspase-3) were measured using western blot analysis. The apoptotic rate of HUVECs was detected using flow cytometry. P. gingivalis HSP60 at a concentration of 10 ng/l significantly decreased the expression levels of VE-cadherin and eNOS protein at 24 h stimulation, whereas no difference in these proteins was identified following a low dose of P. gingivalis HSP60 (1 ng/l). P. gingivalis HSP60 at 100 ng/l significantly downregulated the expression levels of VE-cadherin and eNOS protein at 12 h in HUVECs. However, the cleavage of caspase-3 showed an opposing change at different concentrations. Consistently, P. gingivalis HSP60 induced apoptosis of HUVECs in a concentration-dependent manner. These results indicated that P. gingivalis HSP60 may induce dysfunction and apoptosis in HUVECs via downregulating the expression levels of VE-cadherin and eNOS, and promoting the cleavage of caspase-3. [ABSTRACT FROM AUTHOR]