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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]

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]

Abstract 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

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]

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]

Abstract 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. Graphical Abstract

Abstract 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.

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]

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 qRT-PCR 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^ (−ΔΔCt) 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.

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]

Abstract 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.

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]

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the mammalian central nervous system that has a significant beneficial effect on human health. Traditional microbial GABA synthesis requires continuous oxygen supplementation. Here, a new anaerobic platform for GABA production was established with engineered C. tyrobutyricum ATCC 25755, which is considered an ideal anaerobic microbial-cell factory for bioproduction. Glutamate decarboxylase (GAD) and Class I heat-shock proteins were screened and overexpressed, generating an excellent Ct-pMAG strain for monosodium-glutamate (MSG) tolerance and GABA production, with a GABA titer of 14.26 g/L in serum bottles with the mixed substrate of glucose and MSG. Fed-batch fermentation was carried out in a 5 L bioreactor, achieving 35.57 g/L and 122.34 g/L final titers of GABA by applying the pH-free strategy and the pH-control strategy, respectively using MSG. Finally, a two-stage strategy (growth stage and bioconversion stage) was applied using glutamate acid (L-Glu) and glucose as the substrate, obtaining a 400.32 g/L final titer of GABA with a productivity of 36.39 g/L/h. Overall, this study provides an anaerobic-fermentation platform for high-level bio-GABA production. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a food contaminant that poses serious threats to animal health, including birds. It is also an air pollutant with well-known neurotoxic effects on humans. However, knowledge on the neurotoxic effects of chronic Cd exposure on chicken is limited. Thus, this study assessed the neurotoxic effects of chronic Cd on chicken cerebellum. Chicks were exposed to 0 (control), 35 (low), and 70 (high) mg/kg of Cd for 90 days, and the expression of genes related to the heat-shock response was investigated. The chickens showed clinical symptoms of ataxia, and histopathology revealed that Cd exposure decreased the number of Purkinje cells and induced degeneration of Purkinje cells with pyknosis, and some dendrites were missing. Moreover, Cd exposure increased the expression of heat-shock factors, HSF1, HSF2, and HSF3, and heat-shock proteins, HSP60, HSP70, HSP90, and HSP110. These changes indicate that HSPs improve the tolerance of the cerebellum to Cd. Conversely, the expressions of HSP10, HSP25, and HSP40 were decreased significantly, which indicated that Cd inhibits the expression of small heat-shock proteins. However, HSP27 and HSP47 were upregulated following low-dose Cd exposure, but downregulated under high-dose Cd exposure. This work sheds light on the toxic effects of Cd on the cerebellum, and it may provide evidence for health risks posed by Cd. Additionally, this work also identified a novel target of Cd exposure in that Cd induces cerebellar injury by disrupting the heat-shock response. Cd can be absorbed into chicken's cerebellum through the food chain, which eventually caused cerebellar injury. This study provided a new insight that chronic Cd-induced neurotoxicity in the cerebellum is associated with alterations in heat-shock response–related genes, which indicated that Cd through disturbing heat-shock response induced cerebellar injury. [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]

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 + CD5 lo and CD3 + CD5 hi 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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bongani Motaung reports financial support was provided by National Research Foundation. Andre G Loxton reports financial support was provided by National Research Foundation. Andre G Loxton reports financial support was provided by European and Developing Countries Clinical Trials Partnership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Photothermal therapy is a novel and promising method for cancer treatment due to its controllable property, noninvasive nature, and high selectivity. Nevertheless, tumor recurrence of inflammatory response and tumor tolerance of heat shock protein over-expression remain serious challenges in current photothermal therapy. Additionally, the high dosage requirement of nanomaterial for optimal imaging and therapeutic effect would result in various side effects, organ excretion burdens, and long-term accumulation in the body. In this work, RD/Qu nanoplatform is designed and prepared with near-infrared (NIR) absorbance, high photothermal conversion efficiency, and great chemotherapy effect for synergetic cancer chemo/photothermal therapy at an ultralow-dose. More importantly, both in vitro and in vivo studies demonstrate that it could decrease the expression of HSP70 to fight hyperthermia tumor tolerance and inhibit inflammatory factor COX-2 to suppress tumor recurrence. Therefore, the RD/Qu nanoparticles show excellent outcome in tumor ablation at a quite low dosage, providing a promising avenue for cancer treatment., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier Inc.)

The sweet potato whitefly, Bemisia tabaci (Gennadius), is one of the several species complexes of whitefly that are currently significant agricultural pests. Bemisia tabaci infests more than 600 plant species and thrives under a wide range of temperature conditions. In addition to the direct damage caused by sucking plant sap, it vectors several plant viruses. Heat-shock proteins play a pivotal role in enabling the insect to extend its geographical location, survival, and reproduction under different stress conditions. B. tabaci harbours several endosymbionts under the genera Portiera, Rickettsia, Hamiltonella, Wolbachia, Arsenophonus, Cardinium, and Fritschea that directly or indirectly affect its fitness. By accelerating cuticle biosynthesis and sclerotisation, symbiotic microbes can reduce or enhance tolerance to extreme temperatures and detoxify heavy metals. Thus, symbionts or microbial communities can expand or constrain the abiotic niche space of their host and affect its ability to adapt to changing conditions. The present study delineates the effect of thermal stress on the expression of heat-shock genes and endosymbionts in B. tabaci. Studies of the expression level of heat-shock proteins with the help of quantitative real-time polymerase chain reaction (qRT-PCR) showed that heat- and cold-shock treatment fuels the increased expression of heat-shock proteins (Hsp40 and Hsp70). However, Hsp90 was not induced by a heat- and cold-shock treatment. A significant decrease in the relative titre of secondary endosymbionts, such as Rickettsia, Arsenophonus, and Wolbachia, were recorded in B. tabaci upon heat treatment. However, the titre of the primary symbiont, C. Portiera, was relatively unaffected by both cold and heat treatments. These results are indicative of the fact that Hsp genes and endosymbionts in B. tabaci are modulated in response to thermal stress, and this might be responsible for the adaptation of whitefly under changing climatic scenario.

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]

Abstract 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.

A strategy for acquiring structural information from sparsely isotopically labeled large proteins is illustrated with an application to the E. coli heat-shock protein, HtpG (high temperature protein G), a 145 kDa dimer. It uses 13C-alanine methyl labeling in a perdeuterated background to take advantage of the sensitivity and resolution of Methyl-TROSY spectra, as well as the backbone-centered structural information from 1H-13C residual dipolar couplings (RDCs) of alanine methyl groups. In all, 40 of the 47 expected crosspeaks were resolved and 36 gave RDC data. Assignments of crosspeaks were partially achieved by transferring assignments from those made on individual domains using triple resonance methods. However, these were incomplete and in many cases the transfer was ambiguous. A genetic algorithm search for consistency between predictions based on domain structures and measurements for chemical shifts and RDCs allowed 60% of the 40 resolved crosspeaks to be assigned with confidence. Chemical shift changes of these crosspeaks on adding an ATP analog to the apo-protein are shown to be consistent with structural changes expected on comparing previous crystal structures for apo- and complex- structures. RDCs collected on the assigned alanine methyl peaks are used to generate a new solution model for the apo-protein structure.

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the mammalian central nervous system that has a significant beneficial effect on human health. Traditional microbial GABA synthesis requires continuous oxygen supplementation. Here, a new anaerobic platform for GABA production was established with engineered C. tyrobutyricum ATCC 25755, which is considered an ideal anaerobic microbial-cell factory for bioproduction. Glutamate decarboxylase (GAD) and Class I heat-shock proteins were screened and overexpressed, generating an excellent Ct-pMAG strain for monosodium-glutamate (MSG) tolerance and GABA production, with a GABA titer of 14.26 g/L in serum bottles with the mixed substrate of glucose and MSG. Fed-batch fermentation was carried out in a 5 L bioreactor, achieving 35.57 g/L and 122.34 g/L final titers of GABA by applying the pH-free strategy and the pH-control strategy, respectively using MSG. Finally, a two-stage strategy (growth stage and bioconversion stage) was applied using glutamate acid (L-Glu) and glucose as the substrate, obtaining a 400.32 g/L final titer of GABA with a productivity of 36.39 g/L/h. Overall, this study provides an anaerobic-fermentation platform for high-level bio-GABA production.

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]

Abstract 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.

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]

Main conclusion: The proteome and its time-dependent effects reveal the importance of stress response (including expression regulation of heat-shock proteins) and fatty acid metabolism in cold adaptation and preservation of Hami melon. To better understand the molecular mechanism of how Hami melons respond to low-temperature stress, this study investigated the relevant physiological characteristics, catalytic antibody activity, and quantitative proteomics of Hami melon (Jiashi muskmelon) during low-temperature storage. Jiashi muskmelon was stored inside two refrigerators set at 21 °C (control group) and 3 °C, respectively, for 24 days. Low-temperature storage led to a significantly reduced decay rate, weight loss rate, and loss of relative conductivity. It also maintained fruit firmness, inhibited the production rate of malondialdehyde and H2O2, and induced over-expression of antioxidant enzyme and ATPase. A total of 1064 differentially expressed proteins (DEPs) were identified during low-temperature storage. Stimulation response was the main process in response to low-temperature. To further verify the proteome data, we selected four heat-shock proteins (HSP) displaying relatively high expression levels. Real-time fluorescence PCR results confirmed that HmHSP90 I, HmHSP90 II, HmHSP70, and HmsHSP were significantly up-regulated upon low-temperature induction. These proteins may protect the Hami melon from physiological and cellular damage due to the low-temperature stress by acting alone or synergistically. Additionally, the main enrichment term of the fatty acid metabolism-related DEPs was fatty acid beta oxidation at 21 °C in contrast to fatty acid biosynthesis processes at 3 °C. It is speculated that Hami melon enhances low-temperature adaptability by slowing down the oxidative degradation of fatty acids and synthesizing new fatty acids at low temperatures. This study provides new insights into the mechanism of low-temperature adaptation and preservation in post-harvest Hami melon during cold storage. [ABSTRACT FROM AUTHOR]

Abstract 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 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.

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.

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.

The management of insect pests under fluctuating temperatures has become an interesting area of study due to their ability to stimulate defense mechanisms against heat stress. Therefore, understanding insect's physiological and molecular response to heat stress is of paramount importance for pest management. Aphids are ectothermic organisms capable of surviving in different climatic conditions. This study aimed to determine the effects of short-time heat stress on green peach aphid Myzus persicae under controlled conditions. In this study, short-time heat stress treatments at different temperatures 27, 30, 33, and 36°C with exposure times of 1, 3, 6, and 10 h, respectively, on the activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and oxidants, such as malondialdehyde (MDA) and hydrogen peroxide (H2O2), were determined. The results showed that the short-time heat stress significantly increased the content of MDA of M. persicae by 71, 78, 81, and 86% at 36°C for the exposure times of 1, 3, 6, and 10 h, respectively, compared with control. The content of H2O2 increased by 75, 80, 85, and 88% at 36°C for the exposure times of 1, 3, 6, and 10 h, respectively, compared with the control. The SOD, POD, and CAT activities increased by 61, 76, and 77% for 1 h, 72, 83, and 84% for 3 h, 80, 85, and 86% for 6 h, and 87, 87.6, and 88% for 10 h at 36°C, respectively, compared with control. Again, under short-time heat stress, the transcription levels of Hsp22 , Hsp23 , Hsp27 , SOD , POD , and CAT genes were upregulated compared with control. Our results suggest that M. persicae increased the enzymatic antioxidant activity and heat-shock gene expression as one of the defensive mechanisms in response to heat stresses. [ABSTRACT FROM AUTHOR]

The management of insect pests under fluctuating temperatures has become an interesting area of study due to their ability to stimulate defense mechanisms against heat stress. Therefore, understanding insect’s physiological and molecular response to heat stress is of paramount importance for pest management. Aphids are ectothermic organisms capable of surviving in different climatic conditions. This study aimed to determine the effects of short-time heat stress on green peach aphid Myzus persicae under controlled conditions. In this study, short-time heat stress treatments at different temperatures 27, 30, 33, and 36°C with exposure times of 1, 3, 6, and 10 h, respectively, on the activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and oxidants, such as malondialdehyde (MDA) and hydrogen peroxide (H2O2), were determined. The results showed that the short-time heat stress significantly increased the content of MDA of M. persicae by 71, 78, 81, and 86% at 36°C for the exposure times of 1, 3, 6, and 10 h, respectively, compared with control. The content of H2O2 increased by 75, 80, 85, and 88% at 36°C for the exposure times of 1, 3, 6, and 10 h, respectively, compared with the control. The SOD, POD, and CAT activities increased by 61, 76, and 77% for 1 h, 72, 83, and 84% for 3 h, 80, 85, and 86% for 6 h, and 87, 87.6, and 88% for 10 h at 36°C, respectively, compared with control. Again, under short-time heat stress, the transcription levels of Hsp22, Hsp23, Hsp27, SOD, POD, and CAT genes were upregulated compared with control. Our results suggest that M. persicae increased the enzymatic antioxidant activity and heat-shock gene expression as one of the defensive mechanisms in response to heat stresses.

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]

Three new sesquiterpenes, valerianaterpenes I–III, and eight known compounds have been isolated from the methanol extract of the rhizomes and roots of Valeriana fauriei. The chemical structures of the three new sesquiterpenes were elucidated based on chemical and spectroscopic evidence. The absolute stereochemistry of valerianaterpene I was determined using X-ray crystallography. The cell death-inducing activity of isolated compounds alone or combination with Adriamycin (ADR) was observed by time-lapse cell imaging. Although the isolated compounds did not affect the number of mitotic entry cells and dead cells alone, kessyl glycol, kessyl glycol diacetate, and iso-teucladiol significantly increased the number of dead cells on ADR treated human cervical cancer cells. One of the mechanisms of cell death-inducing activity for the kessyl glycol acetate was suggested to be the inhibition of heat-shock protein 105 (Hsp105) expression level. This paper first deals with the naturally occurring compounds as Hsp105 inhibitor. [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]

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]

Abstract Background Calcific aortic valve disease (CAVD) is an atheroinflammatory process; finally it leads to progressive calcification of the valve. There is no effective pharmacological treatment for CAVD and many of the underlying molecular mechanisms remain unknown. We conducted a proteomic study to reveal novel factors associated with CAVD. Methods We compared aortic valves from patients undergoing valvular replacement surgery due to non-calcified aortic insufficiency (control group, n = 5) to a stenotic group (n = 7) using two-dimensional difference gel electrophoresis (2D-DIGE). Protein spots were identified with mass spectrometry. Western blot and immunohistochemistry were used to validate the results in a separate patient cohort and Ingenuity Pathway Analysis (IPA) was exploited to predict the regulatory network of CAVD. Results We detected an upregulation of complement 9 (C9), serum amyloid P-component (APCS) and transgelin as well as downregulation of heat shock protein (HSP90), protein disulfide isomerase A3 (PDIA3), annexin A2 (ANXA2) and galectin-1 in patients with aortic valve stenosis. The decreased protein expression of HSP90 was confirmed with Western blot. Conclusions We describe here a novel data set of proteomic changes associated with CAVD, including downregulation of the pro-inflammatory cytosolic protein, HSP90.

Abstract Background Taenia multiceps is a harmful tapeworm and its larval form (coenurus cerebralis) is the causative agent of coenurosis, a disease affecting the health of herbivores, resulting in great economic loss to animal husbandry. Heat-shock proteins (HSPs), expressed in all prokaryotes and eukaryotes, act as molecular chaperones and can affect pathogenicity. Methods Herein, cDNAs of T. multiceps genes Tm-HSP60 and Tm-p36 were cloned and molecularly characterised by bioinformatics analyses. The immunogenicity and immunoreactivity of recombinant rTm-HSP60 and rTm-p36 proteins were investigated by immunoblotting and indirect ELISA was established to evaluate their serodiagnostic potential. Tissue localisation and transcriptional level at different life stages of T. multiceps were determined by immunohistochemical and quantitative real-time PCR analyses. Result The 533 residue rTm-HSP60 and the 314 residue rTm-p36 proteins share typical highly conserved features of HSPs. Tm-p36 shares structural characteristics with metazoan small HSPs, with two N-terminal α-crystallin domains. Compared with Tm-p36, Tm-HSP60 displayed stronger immunogenicity, and the indirect ELISA based on rTm-HSP60 exhibited a sensitivity of 83.3% and a specificity of 87.5%, while rTm-p36 was not suitable to develop indirect ELISA. Tm-HSP60 was widely distributed in all stages of T. multiceps, albeit at relatively low levels, while Tm-p36 was specifically distributed in the protoscolex and oncosphere. Conclusions The sequence, structural and functional analyses of these two HSPs indicates that they may play important roles in the life-cycle of T. multiceps as molecular chaperones. Tm-HSP60 displayed stronger immunogenicity compare to Tm-p36, and has the potential for antibody detection. Tm-p36 was strongly associated with the activation of oncospheres and has potential interest for vaccination.

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]

IntroductionRight now, we are facing a global pandemic caused by the coronavirus SARS-CoV-2 that causes the highly contagious human disease COVID-19. The number of COVID-19 cases is increasing at an alarming rate, more and more people suffer from it, and the death toll is on the rise since December 2019, when COVID-19 has presumably appeared. We need an urgent solution for the prevention, treatment, and recovery of the involved patients.MethodsModulated electro-hyperthermia (mEHT) is known as an immuno-supportive therapy in oncology. Our proposal is to apply this method to prevent the progression of the disease after its identification, to provide treatment when necessary, and deliver rehabilitation to diminish the fibrotic—often fatal—consequences of the infection.HypothesisThe effects of mEHT, which are proven for oncological applications, could be utilized for the inactivation of the virus or for treating the fibrotic consequences. The hypothesized mEHT effects, which could have a role in the antiviral treatment, it could be applied for viral-specific immune-activation and for anti-fibrotic treatments.