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Cold stimulation has been shown to regulate glucose, lipid, and amino acid metabolism, while also increasing heat production and energy expenditure in the body. Disordered energy metabolism is a key factor in the onset and progression of chronic metabolic conditiones such as diabetes, obesity, and cardiovascular disease. Recent research has unveiled the myriad pathways through which cold stimulation affects human energy metabolism. This article provides an overview of how cold stimulation affects energy metabolism across the three major metabolic pathways. Furthermore, it explores the implications and potential therapeutic applications of cold stimulation in the prevention and treatment of various metabolic diseases.

ABSTRACT: Improving immune function is an important indicator for establishing cold adaptation in broilers. In the study, to explore the effects and molecular mechanisms of intermittent and mild cold stimulation (IMCS) on the immune function of broilers, CIRP and TRPM8, induced by cold stimulation, as well as the NF-κB and MAPK pathways which play an important role in immune response, were selected to investigate. A total of 192 one-day-old broilers (Ross 308) were selected and randomly divided into the control group (CC) and the cold stimulation group (CS). The broilers in CC were raised at normal feeding temperature from d 1 to 43, while the broilers in CS were subjected to cold stimulation from day 15 to 35, with a temperature 3 °C below that of the CC group for 5 h, at 1 d intervals. The results showed that IMCS had little effect on the broiler hearts, and the myocardial structure was not damaged. On d 22, IMCS significantly increased the mRNA levels of CIRP, TRPM8, P65, P38, COX-2, TNF-α, IFN- γ, IL-6, IL-10, and the protein levels of CIRP, P65, P38, IL-1β and iNOS in the hearts, and the levels of CIRP and all cytokines in the serum (P ≤ 0.05). The mRNA and protein levels of IκB-α were significantly reduced (P ≤ 0.05). On d 36, the mRNA levels of TRPM8, P65, ERK, and IL-10 in the hearts and the content of COX-2 in the serum in CS were increased significantly (P ≤ 0.05), while the mRNA levels of IκB-α, P38, and IL-1β were decreased significantly (P ≤ 0.05). On d 43, IMCS significantly upregulated the mRNA levels of TRPM8, IFN- γ, IL-4, IL-6, IL-10, and the protein levels of IκB-α, P38, and the levels of iNOS, TNF-α, IL6 and IL10 in the serum (P ≤ 0.05); whereas it significantly downregulated CIRP, JNK, P38, iNOS, TNF-α mRNA levels, and CIRP, P65, ERK, JNK, IL1β and iNOS protein levels (P ≤ 0.05). Therefore, IMCS can enhance broiler immune function through co-regulation of CIRP and TRPM8 on the NF-κB and MAPK pathways, which facilitate the cold adaptation in broilers.

Cold stimulation has been linked to acute myocardial infarction and other cardiovascular diseases. Residents in the frigid zones, such Heilongjiang Province, experience a higher incidence of adverse cardiovascular events during winter, posing a significant health threat and increasing the overall medical burden. Cold stimulation serves as an detrimental stressor, inducing inflammation in the body. Therefore, understanding the role of inflammatory responses induced by cold stimulation in the occurrence and development of cardiovascular diseases is of paramount importance. Given the impact of cold on inflammation in cardiovascular diseases and the expanding array of anti-inflammatory methods for the treatment of cardiovascular diseases, delving into the inflammatory responses mediated by can significantly complement cardiovascular disease management. This review explorest the synergistic relationship between cold stimulation and inflammation induction, elucidating how this interplay influences the occurrence and progression of cardiovascular diseases.

Objective: To explore the difference in temperature recovery following cold stimulation between participants with and without diabetes mellitus (DM). Materials and Methods: The participants without (control group; n = 25) and with (DM group; n = 26) DM were subjected to local cold stimulation (10º C for 90 s). The thermal images of their hands were continuously captured using a thermal camera within 7 min following cold stimulation, and the highest temperature of each fingertip was calculated. According to the temperature values at different timepoints, the temperature recovery curves were drawn, and the baseline temperature (T‐base), initial temperature after cooling (T0), temperature decline amplitude (T‐range), and area under the temperature recovery curve > T0 (S) were calculated. Finally, symmetry differences between the two groups were analysed. Results: No statistical differences in the T‐base, T0, and T‐range were observed between the DM and control groups. After drawing the rewarming curve according to the temperature of the fingertips of the patients following cold stimulation, the S in the DM group was significantly lower than that in the control group (p < 0.05). Furthermore, the asymmetry of the base temperature of the hand was observed in the DM group. Conclusions: Following cold stimulation, the patients with DM exhibited a different rewarming pattern than those without DM. Thus, cold stimulation tests under infrared thermography may contribute to the early screening of diabetic peripheral neuropathy in future. [ABSTRACT FROM AUTHOR]

ABSTRACT: To investigate the potential protective effect of prior cold stimulation on broiler intestine induced by acute cold stress (ACS). A total of 384 one-day-old broilers were divided into control (CON), ACS, cold stimulation Ⅰ (CS3+ACS), and cold stimulation Ⅱ (CS9+ACS) groups. Broilers in CON and ACS groups were reared normally, and birds in CS3+ACS and CS9+ACS groups were reared at 3℃ and 9℃ below CON group for 5 h, respectively, on alternate days from d 15 to 35. Broilers in ACS, CS3+ACS, and CS9+ACS groups were subjected to 10℃ for 24 h on d 43. Eventually, small intestine tissues were collected for histopathological observation and indexes detection. The results showed that intestinal tissues in all ACS-broilers exhibited inflammatory cell infiltrates, microvilli disruption, reduced villus length in jejunum and increased crypt depth in jejunum and ileum. Whereas these phenomena were relatively light in CS3+ACS group. Compared to CON group, mRNA expression of the TLR4/MyD88/NF-κB pathway-related genes (TLR4, MyD88, NF-κBp65, COX-2, iNOS, PTGEs, TNF-α), Th1/Th17-derived cytokines (IL-1β, IL-2, IL-8, IL-12, IFN-γ, IL-17), and HSPs (HSP40, HSP60, HSP70, HSP90) was upregulated (P < 0.05), and that of Th2-deviated cytokines (IL-4, IL-6, IL-10, IL-13) and IκBα was downregulated (P < 0.05) in small intestine in almost all ACS-broilers. Compared to ACS group, mRNA expression of most of the TLR4/MyD88/NF-κB pathway-related genes, Th1/Th17-derived cytokines, and HSPs was downregulated and that of Th2-derived cytokines was upregulated in CS3+ACS group (P < 0.05). Protein expression levels of TLR4, MyD88, p-p65/p65, p-IκBα/IκBα, IKK, TNF-α, IL-1β, IL-10, and HSPs were similar to their mRNA expression. The concentration of sIgA and activities of CAT, SOD, and GSH-px were decreased and MDA and H2O2 were increased in ACS and CS9+ACS groups compared to CON group (P < 0.05). Therefore, cold stress caused oxidative stress and inflammation, leading to gut immune dysfunction; while mild cold stimulation at 3℃ below normal rearing temperature alleviated cold stress-induced intestinal injure and dysfunction by modulating the TLR4/MyD88/NF-κB pathway in broilers.

ABSTRACT: To investigate the effect of intermittent cold stimulation on cardiac energy metabolism and cold resistance of broilers, 288 broilers were divided into 3 groups: control group (CC) and 2 cold stimulation groups (CS3 and CS9). The CS3 and CS9 groups received cold stimulation at temperatures of 3°C and 9°C lower than CC group for 5 h from d 15 to 35. Three groups were subjected to acute cold stress (ACS) of 10°C for 12 and 24 h at 44 d. Performance, cardiac histopathological changes, heat shock proteins (HSPs), and lipid metabolism levels were measured. Results showed that the performance was not different among groups at 22 and 29 d (P > 0.05), but the mRNA levels of Acyl CoA synthase long-chain family member 1 (ACSL1) and acyl-coenzyme oxidase (ACO) in CS group were upregulated compared to CC group (P < 0.05). At 36 d, the performance of the CS3 group was better than the other 2 groups, myocardial structure was normal and other lipid metabolism indexes, except for peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) levels, were similar to those of CC group (P > 0.05). The myocardial fiber disorder, Triglyceride (TG), and leptin (LEP) contents were significantly lower in CS9 group than in CC and CS3 groups at 36 d (P < 0.05). The HSP protein levels were significantly higher in CS group than in CC group before ACS (P < 0.05). After 24 h of ACS, the mRNA of lipid metabolism genes, the protein levels of HSP40 and HSP60, and the contents of TG and LEP in the CS3 group were upregulated compared to other groups. The CC and CS9 groups showed myocardial structure was destroyed, with lower TG and LEP levels compared to before ACS (P < 0.05). Therefore, cold stimulation at 3°C lower than the normal feeding temperature for 5 h did not impair performance but can increase the resistance of broilers to ACS by promoting lipid metabolism.

ABSTRACT: To investigate the potential protective effect of intermittent cold stimulation on lung tissues of broilers exposed to acute cold stress (ACS). A total of 384 one-day-old broilers were assigned to 4 experimental groups with 6 replicates of 16 birds each: control (CON) and ACS groups were reared at normal feeding temperature from d 1 to 42; cold treatment groups (CS3+ACS and CS9+ACS) were reared, respectively, at 3°C or 9°C for 5 h on alternate days below the CON group from d 15 to 35. Animals in CS3+ACS, CS9+ACS, and ACS groups were exposed at 10°C for 24 h on d 43. Subsequently, lung tissues were collected to perform histopathological examination and measurement of relevant indexes. The results showed that lung tissues in CS9+ACS and ACS groups exhibited increased inflammatory cell infiltrates and collagen deposition compared to the CON group, while this pathological phenomenon was less pronounced in the CS3+ACS group. Compared to CON group, H2O2 and MDA contents were increased, and the activities of antioxidant enzymes (CAT, SOD, GPx, T-AOC) were reduced in CS9+ACS and ACS group (P < 0.05); mRNA and protein levels of inhibitor of NF-κB, Smad7, matrix metallopeptidase (MMP)-2, MMP9, and antioxidant-related genes were downregulated, whereas mRNA and protein levels of genes related to NF-κB/NLRP3 pathway-regulated inflammation and TGF-β1/Smad pathway-regulated fibrosis were upregulated in cold-stressed broilers (P < 0.05). mRNA levels of heme oxygenase-1, NAD(P)H quinone oxidoreductase-1, and MMP9 were increased in CS3+ACS group (P < 0.05). Moreover, the expression of most antioxidant-related genes was increased, and that of inflammation- and fibrosis-related genes was reduced in CS3+ACS group (P < 0.05). Therefore, cold stress caused oxidative stress and inflammation, leading to pulmonary fibrosis in broilers, whereas intermittent mild cold stimulation at 3°C below normal rearing temperature alleviated fibrosis by inhibiting the TGF-β1/Smad pathway modulated by the Nrf2/HO-1 and NF-κB/NLRP3 signaling pathway. This study suggests that intermittent mild cold stimulation can be a potential strategy to reduce ACS-induced lung damage in broilers.

Incidence rate and mortality rate of acute cardiovascular disease(CVD), especially acute myocardial infarction(AMI)are significantly higher in cold environment. This may be closely related to sympathetic activation, blood viscosity change, coagulation activation, oxidative stress, inflammatory response and other factors affecting plaque stability by cold stimulation. Winter swimming is a kind of sports exposed to extreme cold pressure. People who often engage in winter swimming will have different degrees of cold adaptation, which may provide some protection to cardiovascular system against cold exposure.

The management of chronic kidney disease (CKD) patients in cold areas is an important task in the daily practice of primary medical and health institutions. An important way to reduce the burden of CKD is to achieve early identification of and implement timely intervention on the relevant risk factors. Studies have shown that diet, alcohol, tobacco, air, sedentary and other factors in cold areas have negative impacts on human kidneys; yet, our current understanding of the effect of cold stimulation on CKD remains blurry. This paper introduces the research progress of risk factors related to CKD in cold areas and analytically summarizes the pathogenesis of CKD caused by cold stimulation, aiming to provide a reference work for the prevention, screening, evaluation, and management of CKD in cold areas.

Cold stimulation from skin-fabric-environment system is one of the important factors that need to consider to design clothing for improving fabric comfort in different environments. In this paper, an innovative fabric heat performance testing instrument was built based on a parallel double hotplate system. The cold stimulation process when fabric covers the hotplate has been described at four stages. Subsequently, the maximum hotplate power (Pmax), the minimum hotplate temperature (Tmin) and the fabric equilibrium temperature (Tf) were used to reflect the transient cold stimulation and fabric equilibrium temperature with the different number of fabric layers, fabric water contents and fiber types. The results showed that as the number of fabric layers increased, the cold sensory of the fabric decreased, but the trend was reversed when the number of fabric layers reached five and the fabric equilibrium temperature was decreased as the number of fabric layers rose from one to five. A rise in fabric water content from 0 to 100% resulted in an increasing coldness. In addition, the equilibrium temperature of the fabric was arranged from high to low in the order of water content of 0% > 100% > 80% > 60% > 40% > 20%. For the different fabrics, fiber thermal conductivity helped to reflect its cold sensation, and the equilibrium temperature of the fabric were related to the fabric's thermal insulation properties. [ABSTRACT FROM AUTHOR]

Human brain metabolism is susceptible to temperature changes. It has been suggested that the supraclavicular brown adipose tissue (BAT) protects the brain from these fluctuations by regulating heat production through the presence of uncoupling protein 1 (UCP-1). It remains unsolved whether inter-individual variation in the expression of UCP-1, which represents the thermogenic capacity of the supraclavicular BAT, is linked with brain metabolism during cold stress. Ten healthy human participants underwent 18F-FDG PET scanning of the brain under cold stimulus to determine brain glucose uptake (BGU). On a separate day, an excision biopsy of the supraclavicular fat—the fat proximal to the carotid arteries supplying the brain with warm blood—was performed to determine the mRNA expression of the thermogenic protein UCP-1. Expression of UCP-1 in supraclavicular BAT was directly related to the whole brain glucose uptake rate determined under cold stimulation (rho = 0.71, p = 0.03). In sub-compartmental brain analysis, UCP-1 expression in supraclavicular BAT was directly related to cold-stimulated glucose uptake rates in the hypothalamus, medulla, midbrain, limbic system, frontal lobe, occipital lobe, and parietal lobe (all rho ≥ 0.67, p < 0.05). These relationships were independent of body mass index and age. When analysing gene expressions of BAT secretome, we found a positive correlation between cold-stimulated BGU and DIO2. These findings provide evidence of functional links between brain metabolism under cold stimulation and UCP-1 and DIO2 expressions in BAT in humans. More research is needed to evaluate the importance of these findings in clinical outcomes, for instance, in examining the supporting role of BAT in cognitive functions under cold stress. [ABSTRACT FROM AUTHOR]

Simple Summary: Animal welfare and health will be negatively impacted by cold stress, resulting in decreased production performance, immune imbalance, and decreased antioxidant capacity. Previous studies focused more on the side effects of low temperature, but animals have the ability to adapt to the environment by regulating metabolic and endocrine processes. The objective of this study was to compare cold resistant of broilers with and without cold stimulation training. By detecting the changes in immunoglobulins, cytokines, toll-like receptors, gut barrier genes, and heat shock proteins gene expression levels before and after acute cold stress, the optimal cold training method was finally determined. The results of our study show that cold stimulation training for 6 h with an interval of one day, at 3 °C lower than the conventional temperature, can change the immune function of broilers. This cold stimulation can also lessen the intestinal damage when subjected to acute cold stress. This research offers a theoretical foundation for the regulation of immune function in broilers raised in cold environments, as well as a scientific basis for the development of cold adaptation in broilers. Cold stress will have a negative impact on animal welfare and health. In order to explore the effect of intermittent cold stimulation training on the cold resistance of broilers. Immune-related and intestinal barrier genes were detected before and after acute cold stress (ACS), aiming to find an optimal cold stimulation training method. A total of 240 1-day-old Ross broilers (Gallus) were divided into three groups (G1, G2, and G3), each with 5 replicates (16 chickens each replicate). The broilers of G1 were raised at normal temperature, while the broilers of G2 and G3 were treated with cold stimulation at 3 °C lower than the G1 for 3 h and 6 h from 15 to 35 d, respectively, at one-day intervals. At 50 d, the ambient temperature for all groups was reduced to 10 °C for six hours. The results demonstrated that before ACS, IL6, IL17, TLR21, and HSP40 mRNA levels in G3 were apparently down-regulated (p < 0.05), while IL8 and Claudin-1 mRNA levels were significantly up-regulated compared with G1 (p < 0.05). After ACS, IL2, IL6, and IL8 expression levels in G3 were lower than those in G2 (p < 0.05). Compared to G2, Claudin-1, HSP90 mRNA levels, HSP40, and HSP70 protein levels were increased in G3 (p < 0.05). The mRNA levels of TLR5, Mucin2, and Claudin-1 in G2 and IL6, IL8, and TLR4 in G3 were down-regulated after ACS, while IL2, IL6, and IL17 mRNA levels in G2 and HSP40 protein levels in G3 were up-regulated after ACS (p < 0.05). Comprehensive investigation shows that cold stimulation at 3 °C lower than the normal feeding temperature for six hours at one day intervals can enhanced immune function and maintain the stability of intestinal barrier function to lessen the adverse effects on ACS in broilers. [ABSTRACT FROM AUTHOR]

• 1.NACs, AP2/ERFs, WRKYs, and bHLHs can help D. nobile resist cold stress. • 2. TPP6, DPE1, PGMP, BAM3 genes participate in the synthesis of polysaccharides. • 3. bHLH, MYB and WRKY play a key role in the accumulation of polysaccharides. • 4. Treatment at 0 °C for 4 days can increase the content of flavonoids and polyphenols in D. nobile Temperature affects the growth and accumulation of carbohydrate in plants. To study the response of Dendrobium nobile to cold stimulation, by using room temperature as the control, four low-temperature gradients (8 °C, 4 °C, 0 °C, −4 °C) were set to investigate the physiological changes and polysaccharide content of D. nobile. The results showed that under −4 °C treatment, the plant suffered severe damage and normal physiological activities were inhibited, resulting in inability to grow normally. Meanwhile, treatment at 0 °C for 4 d significantly increased the accumulation of polysaccharides in D. nobile (an increase of 56.18 % compared to CK), and the plant can grow normally after relieving cold stimulation. To explore the mechanism of its promoting polysaccharide accumulation, we conducted transcriptome analysis of D. nobile in this treatment. The results showed that TPP6, DPE1, PGMP, BAM3 genes in the starch and subcrosse metropolis; The pel gene in pentose and glucose conversions and transcription factors such as bHLH, MYB, and WRKY were significantly upregulated, thereby promoting the accumulation of polysaccharides in D. nobile. This study provides new perspective into the low-temperature adaptability of D. nobile and lays the foundation for further research on the biosynthetic pathways of D. nobile polysaccharides. [Display omitted] [ABSTRACT FROM AUTHOR]

Improving immune function is an important indicator for establishing cold adaptation in broilers. In the study, to explore the effects and molecular mechanisms of intermittent and mild cold stimulation (IMCS) on the immune function of broilers, CIRP and TRPM8, induced by cold stimulation, as well as the NF-κB and MAPK pathways which play an important role in immune response, were selected to investigate. A total of 192 one-day-old broilers (Ross 308) were selected and randomly divided into the control group (CC) and the cold stimulation group (CS). The broilers in CC were raised at normal feeding temperature from d 1 to 43, while the broilers in CS were subjected to cold stimulation from day 15 to 35, with a temperature 3 °C below that of the CC group for 5 h, at 1 d intervals. The results showed that IMCS had little effect on the broiler hearts, and the myocardial structure was not damaged. On d 22, IMCS significantly increased the mRNA levels of CIRP, TRPM8, P65, P38, COX-2, TNF-α, IFN- γ, IL-6, IL-10 , and the protein levels of CIRP, P65, P38, IL-1β and iNOS in the hearts, and the levels of CIRP and all cytokines in the serum (P ≤ 0.05). The mRNA and protein levels of IκB-α were significantly reduced (P ≤ 0.05). On d 36, the mRNA levels of TRPM8, P65, ERK, and IL-10 in the hearts and the content of COX-2 in the serum in CS were increased significantly (P ≤ 0.05), while the mRNA levels of IκB-α, P38, and IL-1β were decreased significantly (P ≤ 0.05). On d 43, IMCS significantly upregulated the mRNA levels of TRPM8, IFN- γ, IL-4, IL-6, IL-10 , and the protein levels of IκB-α, P38, and the levels of iNOS, TNF-α, IL6 and IL10 in the serum (P ≤ 0.05); whereas it significantly downregulated CIRP, JNK, P38, iNOS, TNF-α mRNA levels, and CIRP, P65, ERK, JNK, IL1β and iNOS protein levels (P ≤ 0.05). Therefore, IMCS can enhance broiler immune function through co-regulation of CIRP and TRPM8 on the NF-κB and MAPK pathways, which facilitate the cold adaptation in broilers. [ABSTRACT FROM AUTHOR]

While osteoporosis is a chronic disease caused by multiple factors, it is also a risk factor for fractures. At present, numerous risk factors for osteoporosis and secondary fractures have been identified, including sunlight, physical fitness, gender, age, trauma, dietary habits, tobacco, alcohol, drugs, air quality, and genetics. Despite that factors such as long winters, short daylight hours, less daily physical activity, air pollution, low calcium and high salt diet, and sedentary lifestyle could negatively impact the bones of residents in the alpine regions of northern China, the direct effect of low-temperature stimulation on bone growth and development remains unclear. In this study, by reviewing current research progress related to osteoporosis and fracture risk in northern China, we proposed appropriate preventive measures for different risk factors to reduce the occurrence of osteoporosis and fracture in cold areas of northern China.

Objective: Bell's palsy, also referred to as clinical manifestations of unilateral facial nerve palsy, encompasses downward angling of the corners of the mouth, the absence of forehead creases, and unilateral incomplete eyelid closure. The incidence of Bell's palsy has increased progressively in recent years, but the underlying mechanism of its occurrence remains unknown; therefore, it is essential to investigate both the cause and treatment of Bell's palsy. Member 2 of the Subfamily V Transient Receptor Potential Cation Channel is a mechanically and thermally sensitive ion channel that plays a crucial role in neural growth and development. Using a novel modeling technique, we endeavored to develop an animal model of Bell's palsy and determine whether TRPV2 expression is altered throughout the course of a facial nerve injury., Materials and Methods: The rats were categorized into 3 groups, and their facial nerve function was assessed using RT-qPCR, WB, and pathologic testing, respectively, after undergoing unilateral cold air stimulation for 1, 3, and 7 days. TRPV2 expression was identified using these techniques., Results: In response to cold stimulation, rats exhibited facial nerve paralysis symptoms, demyelinating lesions in the facial nerve, and increased TRPV2 expression., Conclusions: Extended cold stimulation of the facial nerve in rats may lead to an imbalance in facial nerve homeostasis and increased TRPV2 expression. These findings will contribute to the understanding of the potential mechanism by which cold stimulation affects the facial nerve. Moreover, this finding implies that TRPV2 could possibly function as an additional diagnostic marker or therapeutic target in the context of Bell's palsy., Competing Interests: Declaration of competing interest The authors 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 Masson SAS.. All rights reserved.)

ABSTRACT: This study aims to assess the effect of intermittent and mild cold stimulation (IMCS) on thymus function and the ability of 1-day-old male Ross 308 broilers to withstand cold. Four hundred broilers were reared under normal and mild cold temperatures at 3°C below the normal feeding temperature and were subjected to acute cold stress (ACS) at 10°C on d 50 at 7 am for 6 h, 12 h, and 24 h. We determined the expression levels of toll-like receptors (TLRs), cytokines and avian β-defencins (AvBDs), encoding genes in thymus of broilers at 22, 36, 43, and 50 d of age, and the serum ACTH and cortisol (CORT) levels at 50 d of age. At D22 and D36, the mRNA expression levels of TLRs and AvBDs genes in CS groups were generally significantly decreased (P < 0.05). The lowest expression levels were found in birds submitted to intermittent and mild cold stimulation training for 5 h (CS5 group) on d 22 and 36 of development (P < 0.05). At D43 and D49 after IMCS, mRNA expression levels of most TLRs and AvBDs were significantly lower than those in CC group (P < 0.05), and that mRNA expression levels of all TLRs and most AvBDs in CS5 group had the same change trend with age as those in CC group (P > 0.05). At D22 and D36, mRNA expression levels of different cytokines in each CS groups were different (P < 0.05). mRNA expression levels of IL-2, IL-4, IL-6, IL-8, IL-17, and IFN-α all reached the highest values in the CS5 group at D36 (P < 0.05). The levels of ACTH and CORT in all IMCS-treated birds changed in varying degrees after ACS, but there was no significant change in CS5 group (P > 0.05). Collectively, different cold stimulation schemes could modulate thymus immune function of broilers by maintaining homeostasis and enhancing cold resistance. In particular, the optimal cold adaptation scheme was at 3°C below the conventional feeding temperature for 5 h.

Peripheral nerves allow a bidirectional communication between brain and adipose tissues, and many studies have clearly demonstrated that a loss of the adipose nerve supply results in tissue dysfunction and metabolic dysregulation. Neuroimmune cells closely associate with nerves in many tissues, including subcutaneous white adipose tissue (scWAT). However, in scWAT, their functions beyond degrading norepinephrine in an obese state remain largely unexplored. We previously reported that a myeloid-lineage knockout (KO) of brain-derived neurotrophic factor (BDNF) resulted in decreased innervation of scWAT, accompanied by an inability to brown scWAT after cold stimulation, and increased adiposity after a high-fat diet. These data underscored that adipose tissue neuroimmune cells support the peripheral nerve supply to adipose and impact the tissue's metabolic functions. We also reported that a subset of myeloid-lineage monocyte/macrophages (Ly6c+CCR2+Cx3cr1+) is recruited to scWAT in response to cold, a process known to increase neurite density in adipose and promote metabolically healthy processes. These cold-induced neuroimmune cells (CINCs) also expressed BDNF. Here we performed RNAseq on CINCs from cold-exposed and room temperature-housed mice, which revealed a striking and coordinated differential expression of numerous genes involved in neuronal function, including neurotrophin signaling and axonal guidance, further supporting that CINCs fulfill a nerve-supporting role in adipose. The increased expression of leukocyte transendothelial migration genes in cold-stimulated CINCs also confirms prior evidence that they are recruited to scWAT and are not tissue resident. We now provide whole-depot imaging of scWAT from LysM-BDNF KO mice, revealing a striking reduction of innervation across the depot fitting with their reduced energy expenditure phenotype. By contrast, Cx3cr1-BDNF KO mice (a macrophage subset of LysM+ cells) exhibited increased thermogenesis and energy expenditure, with compensatory increased food intake and no change in adiposity or body weight. While these KO mice also exhibit a significantly reduced innervation of scWAT, especially around the subiliac lymph node, they displayed an increase in small fiber sympathetic neurite branching, which may underlie their increased thermogenesis. We propose a homeostatic role of scWAT myeloid-lineage neuroimmune cells together in nerve maintenance and neuro-adipose regulation of energy expenditure. [ABSTRACT FROM AUTHOR]

Human brain metabolism is susceptible to temperature changes. It has been suggested that the supraclavicular brown adipose tissue (BAT) protects the brain from these fluctuations by regulating heat production through the presence of uncoupling protein 1 (UCP-1). It remains unsolved whether inter-individual variation in the expression of UCP-1, which represents the thermogenic capacity of the supraclavicular BAT, is linked with brain metabolism during cold stress. Ten healthy human participants underwent 18F-FDG PET scanning of the brain under cold stimulus to determine brain glucose uptake (BGU). On a separate day, an excision biopsy of the supraclavicular fat—the fat proximal to the carotid arteries supplying the brain with warm blood—was performed to determine the mRNA expression of the thermogenic protein UCP-1. Expression of UCP-1 in supraclavicular BAT was directly related to the whole brain glucose uptake rate determined under cold stimulation (rho = 0.71, p = 0.03). In sub-compartmental brain analysis, UCP-1 expression in supraclavicular BAT was directly related to cold-stimulated glucose uptake rates in the hypothalamus, medulla, midbrain, limbic system, frontal lobe, occipital lobe, and parietal lobe (all rho ≥ 0.67, p < 0.05). These relationships were independent of body mass index and age. When analysing gene expressions of BAT secretome, we found a positive correlation between cold-stimulated BGU and DIO2. These findings provide evidence of functional links between brain metabolism under cold stimulation and UCP-1 and DIO2 expressions in BAT in humans. More research is needed to evaluate the importance of these findings in clinical outcomes, for instance, in examining the supporting role of BAT in cognitive functions under cold stress.

Enhanced brown adipose tissue (BAT) mass and activity have been demonstrated to promote the expenditure of excess stored energy and reduce prevalence of obesity. Cold is known as a potent stimulator of BAT and activates BAT primarily through the β3- adrenergic-cAMP signaling. Here, we performed RNA-sequencing to identify differential miRNAs in mouse BAT upon cold exposure and a total of 20 miRNAs were validated. With the treatment of CL-316,243 (CL) and forskolin (Fsk) in mouse a nd human differentiated brown adipocyte cells in vitro, miR-23b-5p, miR-133a-3p, miR-135-5p, miR-491-5p, and miR-150-3p expression decreased and miR-455-5p expression increased. Among these deferentially expressed miRNAs, miR-23b-5p expression was differentially regulated in activated and aging mouse BAT and negatively correlated with Ucp1 expression. Overexpression of miR-23b-5p in the precursor cells from BAT re vealed no significant effects on lipid accumulation, but diminished mitochondrial func tion and decreased expression of BAT specific markers. Though luciferase reporter a ssays did not confirm the positive association of miR-23b-5p with the 3′UTRs of the predicted target Ern1, miR-23b-5p overexpression may affect brown adipocyte thermogenic capacity mainly through regulating genes expression involving in lipolysis and fatty acid β-oxidation pathways. Our results suggest that miRNAs are involved in cold-mediated BAT thermogenic activation and further acknowledged miR-23b-5p as a negative regulator in controlling thermogenic programs, further providing potential molecular therapeutic targets to increase surplus energy and treat obesity.

ABSTRACT: The effects of long-term cold stimulation on the immune function of ileum and adaptability to cold stress in broilers were examined. A total of 360 Arbor Acres broilers was divided into 3 groups and four replicates per group. C (control) was reared in normal thermal environment. C-3 and C-12 (treatments) were kept in cold condition of 3 or 12°C lower than the temperature of C from days 8 to 42. At day 42, all the groups were exposed to an acute cold stress challenge, designated as S, S-3, and S-12. The mRNA levels of immune molecules and heat shock proteins as well as oxidative stress-related indicators in ileum tissues, and immunoglobulins contents in serum were examined at 14, 42, and 43 d of age. The C-3 regimen had no adverse effect on production performance, whereas the C-12 regimen reduced the production performance relative to C (P < 0.05). At day 42, C-3 had higher levels of immune indexes (P < 0.05), whereas C-12 had lower levels than C (P < 0.05). No differences in levels of oxidative stress-related indicators were found between C and C-3 at day 42 (P > 0.05). S-3 had higher levels of immune indexes and lower levels of oxidative stress-related indicators (P < 0.05), as compared to S and S-12. The results suggest that 34 d of cold stimulation at 3°C lower than the normal temperature had no adverse impacts on production performance but enhanced the immunity of ileum and adaptability to acute cold challenge in broilers.

Cold stress will have a negative impact on animal welfare and health. In order to explore the effect of intermittent cold stimulation training on the cold resistance of broilers. Immune-related and intestinal barrier genes were detected before and after acute cold stress (ACS), aiming to find an optimal cold stimulation training method. A total of 240 1-day-old Ross broilers (Gallus) were divided into three groups (G1, G2, and G3), each with 5 replicates (16 chickens each replicate). The broilers of G1 were raised at normal temperature, while the broilers of G2 and G3 were treated with cold stimulation at 3 °C lower than the G1 for 3 h and 6 h from 15 to 35 d, respectively, at one-day intervals. At 50 d, the ambient temperature for all groups was reduced to 10 °C for six hours. The results demonstrated that before ACS, IL6, IL17, TLR21, and HSP40 mRNA levels in G3 were apparently down-regulated (p < 0.05), while IL8 and Claudin-1 mRNA levels were significantly up-regulated compared with G1 (p < 0.05). After ACS, IL2, IL6, and IL8 expression levels in G3 were lower than those in G2 (p < 0.05). Compared to G2, Claudin-1, HSP90 mRNA levels, HSP40, and HSP70 protein levels were increased in G3 (p < 0.05). The mRNA levels of TLR5, Mucin2, and Claudin-1 in G2 and IL6, IL8, and TLR4 in G3 were down-regulated after ACS, while IL2, IL6, and IL17 mRNA levels in G2 and HSP40 protein levels in G3 were up-regulated after ACS (p < 0.05). Comprehensive investigation shows that cold stimulation at 3 °C lower than the normal feeding temperature for six hours at one day intervals can enhanced immune function and maintain the stability of intestinal barrier function to lessen the adverse effects on ACS in broilers.

Procyanidin B2 (PB2), a naturally occurring flavonoid abundant in a wide range of fruits, has been shown to exert antioxidant, anti‐inflammatory and anticancer properties. However, the role of PB2 in the prevention of cold stimulation (CS)‐induced liver injury. The present study was undertaken to determine the effects of PB2 on liver injury induced by cold stimulation and its potential molecular mechanisms. The present study results showed that treatment with PB2 significantly reduced CS‐induced liver injury by alleviating histopathological changes and serum levels of alanine transaminase and aspartate transaminase. Moreover, treatment with PB2 inhibited secretion of inflammatory cytokines and oxidative stress in cold‐stimulated mice. PB2 reduced cold stimulation‐induced inflammation by inhibiting TLR4/NF‐κB and Txnip/NLRP3 signalling. Treatment with PB2 reduced oxidative stress by activating Nrf‐2/Keap1, AMPK/GSK3β signalling pathways and autophagy. Furthermore, simultaneous application of Shh pathway inhibitor cyclopamine proved that PB2 targets the Hh pathway. More importantly, co‐treatment with PB2 and cyclopamine showed better efficacy than monotherapy. In conclusion, our findings provide new evidence that PB2 has protective potential against CS‐induced liver injury, which might be closely linked to the inhibition of Shh signalling pathway. [ABSTRACT FROM AUTHOR]

To investigate the potential protective effect of prior cold stimulation on broiler intestine induced by acute cold stress (ACS). A total of 384 one-day-old broilers were divided into control (CON), ACS, cold stimulation Ⅰ (CS3+ACS), and cold stimulation Ⅱ (CS9+ACS) groups. Broilers in CON and ACS groups were reared normally, and birds in CS3+ACS and CS9+ACS groups were reared at 3℃ and 9℃ below CON group for 5 h, respectively, on alternate days from d 15 to 35. Broilers in ACS, CS3+ACS, and CS9+ACS groups were subjected to 10℃ for 24 h on d 43. Eventually, small intestine tissues were collected for histopathological observation and indexes detection. The results showed that intestinal tissues in all ACS-broilers exhibited inflammatory cell infiltrates, microvilli disruption, reduced villus length in jejunum and increased crypt depth in jejunum and ileum. Whereas these phenomena were relatively light in CS3+ACS group. Compared to CON group, mRNA expression of the TLR4/MyD88/NF-κB pathway-related genes (TLR4, MyD88, NF-κBp65, COX-2, iNOS, PTGEs, TNF-α), Th1/Th17-derived cytokines (IL-1β, IL-2, IL-8, IL-12, IFN-γ, IL-17), and HSPs (HSP40, HSP60, HSP70, HSP90) was upregulated (P < 0.05), and that of Th2-deviated cytokines (IL-4, IL-6, IL-10, IL-13) and IκBα was downregulated (P < 0.05) in small intestine in almost all ACS-broilers. Compared to ACS group, mRNA expression of most of the TLR4/MyD88/NF-κB pathway-related genes, Th1/Th17-derived cytokines, and HSPs was downregulated and that of Th2-derived cytokines was upregulated in CS3+ACS group (P < 0.05). Protein expression levels of TLR4, MyD88, p-p65/p65, p-IκBα/IκBα, IKK, TNF-α, IL-1β, IL-10, and HSPs were similar to their mRNA expression. The concentration of sIgA and activities of CAT, SOD, and GSH-px were decreased and MDA and H 2 O 2 were increased in ACS and CS9+ACS groups compared to CON group (P < 0.05). Therefore, cold stress caused oxidative stress and inflammation, leading to gut immune dysfunction; while mild cold stimulation at 3℃ below normal rearing temperature alleviated cold stress-induced intestinal injure and dysfunction by modulating the TLR4/MyD88/NF-κB pathway in broilers. [ABSTRACT FROM AUTHOR]

Background: Brown adipose tissue (BAT) is essential to maintain body temperature. Its ability to convert chemical energy in glucose and free fatty acids to heat is conferred by a unique protein, UCP‐1. BAT activity is greatest in children and adolescents, declining through adulthood. Blood glucose concentrations outside the normal nondiabetic range are common in type 1 diabetes and hyperglycaemia leads to insulin resistance in muscle and white adipose tissue, but whether this applies to BAT, is not known. Method: To investigate the effect of type 1 diabetes on BAT activity, we measured the supraclavicular temperature of 20 children with type 1 diabetes and compared them to 20 age‐matched controls, using infrared thermography. Results: The diabetes group had lower stimulated supraclavicular temperatures (diabetes group: 35.03 (34.76–35.30)°C; control group: 35.42 (35.16–35.69)°C; p = 0.037) and a reduced response in relative temperature following cold stimulation, after adjusting for BMI (diabetes group: 0.11 (0.03–0.18)°C; control group: 0.22 (0.15–0.29)°C; p = 0.034). In the diabetes group, there was no association between glycaemic measures and supraclavicular temperatures, but the method of insulin delivery may significantly affect the change in supraclavicular temperature with stimulation (injections: 0.01 (−0.07–0.09)°C; pump: 0.15 (0.04–0.26)°C; p = 0.028). Conclusions: While further work is needed to better understand the glucose‐insulin‐BAT relationship, one possible explanation for the reduced supraclavicular temperature is that exogenous, unlike endogenous, insulin, is not suppressed by the activity of the sympathetic nervous system, preventing lipolysis‐driven activation of BAT. [ABSTRACT FROM AUTHOR]

In this study, we investigated the effects of menthol application on the cortical and cutaneous silent period (CSP/cutSP). Both the cutSP and CSP were assessed while participants (n = 11, young adults) exerted a light contraction with the right thumb. In the 1st block of trials, SPs were measured after the application of a Neutral gel (Aloe Vera) to the dorsal aspect of the hand. In the 2nd block, the same measures were repeated following a Menthol gel (4%) application. Subjective ratings of cooling sensations were obtained for each block. The Neutral gel was consistently perceived as slightly cool by participants, wheres the Menthol gel elicited sensations from cool to very cold. Paired t-tests showed no difference in the cutSP duration between the two conditions, whereas a significant increase in the CSP was detected with the Menthol condition. No correlation was found between changes in the CSP and those of the cutSP. These results highlight the difference between the cutSP and the CSP, as inhibitory phenomena, and point to a cortical contribution to the soothing effects associated with topical menthol applications. [ABSTRACT FROM AUTHOR]

Bell's palsy is the most common condition involving a rapid and unilateral onset of peripheral paresis/paralysis of the seventh cranial nerve. It affects 11.5–53.3 per 100,000 individuals a year across different populations. Bell's palsy is a health issue causing concern and has an extremely negative effect on both patients and their families. Therefore, diagnosis and prompt cause determination are key for early treatment. However, the etiology of Bell's palsy is unclear, and this affects its treatment. Thus, it is critical to determine the causes of Bell's palsy so that targeted treatment approaches can be developed and employed. This article reviews the literature on the diagnosis of Bell's palsy and examines possible etiologies of the disorder. It also suggests that the diagnosis of idiopathic facial palsy is based on exclusion and is most often made based on five factors including anatomical structure, viral infection, ischemia, inflammation, and cold stimulation responsivity. [ABSTRACT FROM AUTHOR]

The effect of cold stress on blood pressure, heart rate, and heart rate variability (HRV) was studied in 80 young men with normal pressure and prehypertensive status from different geographical areas: Ukraine, West Africa, Arab countries, and India. It was found that under cold stress systolic, diastolic pressure and heart rate increased simultaneously only in prehypertensive Ukrainians and Indians. Thus, they significantly increased the activity of the sympathetic nervous system and/or had hyperreactivity of the cardiovascular system and lack of baroreflex regulation. In Africans and Arabs, the response of the cardiovascular system and HRV to the cold pressor test were not statistically significant, which may be a manifestation of decreased sensitivity of cold and pain receptors or inhibition of another part of cardiovascular reflex regulation. In normotensive Indians the high- and low-frequency power of the HRV spectrum increased from 6.558 ± 0.464 and 6.518 ± 0.382 to 7.246 ± 0.429 and 7.005 ± 0.322 Lnms2, respectively. This indicates an increase of the activity of parasympathetic nervous system and a tendency to increase the activity of barorefex during the cold test. [ABSTRACT FROM AUTHOR]

To investigate the potential protective effect of intermittent cold stimulation on lung tissues of broilers exposed to acute cold stress (ACS). A total of 384 one-day-old broilers were assigned to 4 experimental groups with 6 replicates of 16 birds each: control (CON) and ACS groups were reared at normal feeding temperature from d 1 to 42; cold treatment groups (CS3+ACS and CS9+ACS) were reared, respectively, at 3°C or 9°C for 5 h on alternate days below the CON group from d 15 to 35. Animals in CS3+ACS, CS9+ACS, and ACS groups were exposed at 10°C for 24 h on d 43. Subsequently, lung tissues were collected to perform histopathological examination and measurement of relevant indexes. The results showed that lung tissues in CS9+ACS and ACS groups exhibited increased inflammatory cell infiltrates and collagen deposition compared to the CON group, while this pathological phenomenon was less pronounced in the CS3+ACS group. Compared to CON group, H 2 O 2 and MDA contents were increased, and the activities of antioxidant enzymes (CAT, SOD, GPx, T-AOC) were reduced in CS9+ACS and ACS group (P < 0.05); mRNA and protein levels of inhibitor of NF-κB, Smad7, matrix metallopeptidase (MMP)-2, MMP9, and antioxidant-related genes were downregulated, whereas mRNA and protein levels of genes related to NF-κB/NLRP3 pathway-regulated inflammation and TGF-β1/Smad pathway-regulated fibrosis were upregulated in cold-stressed broilers (P < 0.05). mRNA levels of heme oxygenase-1, NAD(P)H quinone oxidoreductase-1, and MMP9 were increased in CS3+ACS group (P < 0.05). Moreover, the expression of most antioxidant-related genes was increased, and that of inflammation- and fibrosis-related genes was reduced in CS3+ACS group (P < 0.05). Therefore, cold stress caused oxidative stress and inflammation, leading to pulmonary fibrosis in broilers, whereas intermittent mild cold stimulation at 3°C below normal rearing temperature alleviated fibrosis by inhibiting the TGF-β1/Smad pathway modulated by the Nrf2/HO-1 and NF-κB/NLRP3 signaling pathway. This study suggests that intermittent mild cold stimulation can be a potential strategy to reduce ACS-induced lung damage in broilers. [ABSTRACT FROM AUTHOR]

To investigate the effect of intermittent cold stimulation on cardiac energy metabolism and cold resistance of broilers, 288 broilers were divided into 3 groups: control group (CC) and 2 cold stimulation groups (CS3 and CS9). The CS3 and CS9 groups received cold stimulation at temperatures of 3°C and 9°C lower than CC group for 5 h from d 15 to 35. Three groups were subjected to acute cold stress (ACS) of 10°C for 12 and 24 h at 44 d. Performance, cardiac histopathological changes, heat shock proteins (HSPs), and lipid metabolism levels were measured. Results showed that the performance was not different among groups at 22 and 29 d (P > 0.05), but the mRNA levels of Acyl CoA synthase long-chain family member 1 (ACSL1) and acyl-coenzyme oxidase (ACO) in CS group were upregulated compared to CC group (P < 0.05). At 36 d, the performance of the CS3 group was better than the other 2 groups, myocardial structure was normal and other lipid metabolism indexes, except for peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) levels, were similar to those of CC group (P > 0.05). The myocardial fiber disorder, Triglyceride (TG), and leptin (LEP) contents were significantly lower in CS9 group than in CC and CS3 groups at 36 d (P < 0.05). The HSP protein levels were significantly higher in CS group than in CC group before ACS (P < 0.05). After 24 h of ACS, the mRNA of lipid metabolism genes, the protein levels of HSP40 and HSP60, and the contents of TG and LEP in the CS3 group were upregulated compared to other groups. The CC and CS9 groups showed myocardial structure was destroyed, with lower TG and LEP levels compared to before ACS (P < 0.05). Therefore, cold stimulation at 3°C lower than the normal feeding temperature for 5 h did not impair performance but can increase the resistance of broilers to ACS by promoting lipid metabolism. [ABSTRACT FROM AUTHOR]

Acclimation can alleviate the damage caused by adverse environmental factors. To investigate the effects of cold stimulation on immunity in tracheal of broilers, 360 one‐day‐old chicks were raised at normal temperatures during 1–7 days. From 8 day, G1 (control) continued to be raised at normal temperatures, whereas G2 and G3 (treatment groups) were cold‐stimulated at 3°C and 12°C below the temperature of G1, respectively. At 42 day, all the groups were subjected to a 24‐hr acute cold stress, designated as S1, S2, and S3. Tracheal tissues were collected to detect gene levels of immunoglobulins, antimicrobial peptides, Hsps, and cytokines, and oxidative stress‐related indicators at 14 day, 42 day, and 43 day, and protein levels of Hsps and proinflammatory cytokines as well as morphology changes at 42 day and 43 day. The results showed that, compared with 42G1, tracheal structure of 42G2 was basically intact, and gene levels of immunoglobulins and antimicrobial peptides increased (p < 0.05), whereas tracheal structure of 42G3 was destroyed, with decreased levels of immunoglobulins (p < 0.05), and increased levels of Hsps and proinflammatory cytokines (p < 0.05). At 43 day, tracheal damage was visible and gene levels of immunoglobulins and antimicrobial peptides decreased in S1 (p < 0.05). Tracheal structure was relatively intact and gene levels of antimicrobial peptides increased in S2 (p < 0.05). Compared with S1 and S3, immune‐related gene levels in S2 were higher, and Hsps and proinflammatory cytokines levels were lower. The results demonstrate that cold stimulation of lower 3°C from 8 to 42 day led to cold acclimation, which improved immunity of tracheal mucosa and resistance to cold stress in broilers. We found that cold stimulation environment of 3°C lower than normal from 8 to 42 days of age could make the chicken establish cold acclimation. Cold acclimation improved immune function of trachea and the resistance to cold stress of the birds to a certain extent Cold acclimation effectively alleviated oxidative stress induced by cold stress and reduced levels of heat shock proteins, which may be a protective mechanism of cold acclimation. [ABSTRACT FROM AUTHOR]

Objective: Here, we wanted to investigate the role of cold stimulation in regulating fat tissue browning and whole body lipid metabolism in mice. Methods: The mice were maintained at 4 ℃ for 1 week. Mice body weight was measured. Fat tissues were collected and fixed for HE staining. Serum levels of TAG, FFA and glycerol were measured. Fat tissue TAG content and protein expression profile were analyzed. Results: Compared to control mice, the body weight of mice was reduced after cold-stimulation for 1 week.The serum levels of triglyceride, free fatty acids and glycerol were decreased. The TAG contents in SWAT(subcutaneous white adipose tissue), GWAT(gonadal visceral white adipose tissue) and BAT(brown adipose tissue) were dramatically reduced in cold-stimulated mice, especially nearly 50 % reduction in SWAT and BAT. Browning phenotype was observed in SWAT of cold-stimulated mice with the appearance of adipocytes with multilocular lipid droplets and high expression of UCP1(uncoupling protein 1) and Cidea. Lipid droplets in GWAT were still unilocular under cold stimulation. The size of lipid droplet was reduced in GWAT with 14% reduction in TAG content under cold stimulation. The expression of UCP1 and Cidea was not significant induced in GWAT, indicating that browning did not occur in GWAT. The BAT of cold-stimulated mice had smaller lipid droplets and higher expression of UCP1. Higher expression of CPT1(Carnitine palmitoyltransferase I) in SWAT, GWAT and BAT of cold-stimulated mice was observed. Conclusion: Cold stimulation could dramatically affect the lipid metabolism status of mice. Whole body fat accumulation was dramatically reduced in cold-stimulated mice. Browning occurred in SWAT with the induction expression of UCP1 and Cidea. All fat tissue showed elevated expression of CPT1, a mitochondrial related protein. [ABSTRACT FROM AUTHOR]

Acclimation can alleviate the negative impacts of adverse environmental factors on an organism. To investigate the effects of prior cold stimulation on inflammatory and immune regulation in ileum of cold-stressed broilers, 360 1-d-old chicks (Arbor Acres) were divided into 3 groups (G1, G2, G3) and raised at normal (thermal comfort) temperatures during 1 to 7 d. From 8 d, G1 (control) continued to be raised at normal temperatures, whereas G2 and G3 (treatments) were cold-stimulated at 3°C and 12°C, respectively, below the temperature of G1, but not below 17°C (reached at 32 d in G2 and 14 d in G3). At 42 d, all the groups were subjected to a 24-h acute cold stress of 7°C, designated as S1, S2, and S3. Ileum tissues and serum of the birds were collected at 42 d and 43 d to detect the levels of pro-inflammatory and immune-related factors as well as morphology changes. At 42 d, ileum of G1 and G2 had intact morphological structure and clear outline, with no differences in levels of iNOS, NF-κB, COX-2, PTGEs, TNF-α, IFN-γ, or IL-4 (P > 0.05). G3 ileum suffered inflammatory injuries, with levels of iNOS, COX-2, PTGEs, TNF-α, and IL-4 being higher than those of G1 (P < 0.05). At 43 d, compared with G1, S1 had severely damaged ileum, increased levels of iNOS, NF-κB, COX-2, PTGEs, TNF-α, and IL-4 (P < 0.05), but decreased level of IFN-γ (P < 0.05). The morphological structure of S2 was intact, and there were no differences between G2 and S2 in levels of NF-κB, PTGEs, TNF-α, IFN-γ, or IL-4 (P > 0.05). Compared with S1, S2 had decreased levels of iNOS, NF-κB, COX-2, PTGEs, TNF-α, and IL-4 (P < 0.05), but increased level of IFN-γ (P < 0.05). There were no differences between G1 and S2 in levels of NF-κB, PTGEs, TNF-α, IFN-γ, or IL-4 (P > 0.05). The results demonstrate that a 3°C-lower-than-normal temperature stimulation of the broilers from 8 to 42 d led to cold acclimation. This prior cold acclimation effectively alleviated elevation of pro-inflammatory cytokines and Th1/Th2 imbalance of the birds induced by subsequent cold stress. [ABSTRACT FROM AUTHOR]

Appropriate cold stimulation can improve immune function and stress tolerance in broilers. In order to investigate the effect of intermittent mild cold stimulation on the intestinal immunity of broilers, 240 healthy one-day-old Ross 308 chickens were randomly divided into three groups: the control group (CC) housed in climatic chambers under usual rearing ambient temperature with a gradual 3.5 °C decrease per week; group II (C3) and group III (C6) to which cold stimulation at 3 °C below the temperature used in CC was applied every two days for 3 and 6 h, respectively, from day 15 to 35, and at the same temperature used in CC from day 35 to 43. The mRNA expression levels of immunoglobulins (IgA and IgG), cytokines (IL2, IL6, IL8, IL17, and IFNγ), and Toll-like receptors (TLR2, TLR4, TLR5, TLR7, and TLR21) were investigated in duodenum, jejunum, and ileum tissue samples on days 22, 29, 35, and 43. From day 15 to 35, mRNA expression of IL2 and IFNγ was increased in the intestine of broilers. After one week of cold stimulation on day 43, mRNA levels of immunoglobulins, cytokines, and Toll-like receptors (TLRs) stabilized. Collectively, the findings indicate that cold stimulation at 3 °C below the usual rearing temperature had a positive impact on intestinal immunity of broilers.

Cold stress causes growth performance to decrease and increases production costs. Cold adaptation can enhance immune function and alleviate the negative impact caused by the stress condition. The study investigated the effect of intermittent and mild cold stimulation on the immune function of the bursa of Fabricius in broilers. A total of 400 healthy one-day-old broilers were divided into the control group (CC) and cold stimulation (CS) groups. The CC group was raised at a conventional raising temperature of broilers, while the CS groups were raised at 3°C below the temperature of the CC for three-, four-, five-, or six-hour periods at one-day intervals from 15 to 35 days of age (D35), denoted CS3, CS4, CS5, and CS6, respectively. Subsequently, they were raised at 20°C from 36 to 49 days of age (D49). The expression levels of TLRs, cytokines, and AvBDs were determined to access the immune function of bursa in broilers. After 21-day IMCS (at D36), the expression levels of TLR1, TLR15 and TLR21, interleukin (IL)-8, and interferon (IFN)-γ, as well as AvBD8 in CS groups, were lower than those in CC (p < 0.05). The expression levels of TLR3, TLR4 and TLR7, were decreased in the CS3, CS5, and CS6 groups (p < 0.05), but there were no significant differences in both the CC and CS4 groups (p > 0.05). When the IMCS ended for 14 days (at D49), the expression levels of TLR2, TLR3, TLR5, TLR7, TLR15, and TLR21, and IL-8, as well as AvBD2, AvBD4 and AvBD7 in CS groups, were lower than those in CC (p < 0.05). In addition to CS4, the expression levels of TLR1, IFN-γ, and AvBD8 in CS3, CS5, and CS6 were still lower than those in CC (p < 0.05). We concluded that the intermittent and mild cold stimulation could regulate immunoreaction by modulating the production of TLRs, cytokines, and AvBDs in the bursa, which could help broilers adapt to low ambient temperature and maintain homeostasis.

To investigate the effects of acute cold stress (ACS) on chicken heart after cold stimulation, female broilers were raised in either normal (C) or gradually decreasing temperatures (CS I and CS II) for 34 days followed by a 24 h ACS at 7°C. Cardiac tissues were collected from the pre-ACS and ACS time points to analyze the histopathological changes, antioxidant status and the expression of heat shock proteins, inflammatory factors and immune-related cytokines. The CS II heart tissues showed shrunken cell membranes and nuclei, disordered or ruptured myocardial fibers, higher MDA content and upregulation in HSP27, HSP40, HSP70, NF-κB, COX-2, PTGEs, iNOS, TNF-α and IL-4 mRNAs, and in protein levels of HSP40, NF-κB and iNOS and reduction in CAT, GSH-px and SOD activity, as well as HSP90 and IFN-γ levels compared to the control tissues before ACS. In contrast, the HSPs were significantly increased, and the inflammatory and immune related factors were unaltered prior to the ACS in the CS I compared to the C group. Following ACS, MDA content was significantly increased and antioxidant activity was significantly decreased in the CS I and CS II groups compared to the C group. The levels of HSP27, HSP70, HSP90, inflammatory factors and IL-4 were significantly reduced and that of IFN-γ was significantly increased in CS I broiler hearts; the reverse trends were seen in CS II relative to CS I. Compared to the pre-ACS levels, that of HSP27, HSP40, HSP60, inflammatory factors and IL-4 were increased and IFN-γ was decreased in the C and CS II groups after ACS. Therefore, cold stimulation at drastically lower temperatures induced cardiac damage, which was further aggravated by ACS. In contrast, cold stimulation at only 3°C lower than normal temperature improved the adaptability of the broilers to ACS.

To investigate the effects of acute cold stress (ACS) on chicken heart after cold stimulation, female broilers were raised in either normal (C) or gradually decreasing temperatures (CS I and CS II) for 34 days followed by a 24 h ACS at 7°C. Cardiac tissues were collected from the pre-ACS and ACS time points to analyze the histopathological changes, antioxidant status and the expression of heat shock proteins, inflammatory factors and immune-related cytokines. The CS II heart tissues showed shrunken cell membranes and nuclei, disordered or ruptured myocardial fibers, higher MDA content and upregulation in HSP27, HSP40, HSP70, NF-κB, COX-2, PTGEs, iNOS, TNF-α and IL-4 mRNAs, and in protein levels of HSP40, NF-κB and iNOS and reduction in CAT, GSH-px and SOD activity, as well as HSP90 and IFN-γ levels compared to the control tissues before ACS. In contrast, the HSPs were significantly increased, and the inflammatory and immune related factors were unaltered prior to the ACS in the CS I compared to the C group. Following ACS, MDA content was significantly increased and antioxidant activity was significantly decreased in the CS I and CS II groups compared to the C group. The levels of HSP27, HSP70, HSP90, inflammatory factors and IL-4 were significantly reduced and that of IFN-γ was significantly increased in CS I broiler hearts; the reverse trends were seen in CS II relative to CS I. Compared to the pre-ACS levels, that of HSP27, HSP40, HSP60, inflammatory factors and IL-4 were increased and IFN-γ was decreased in the C and CS II groups after ACS. Therefore, cold stimulation at drastically lower temperatures induced cardiac damage, which was further aggravated by ACS. In contrast, cold stimulation at only 3°C lower than normal temperature improved the adaptability of the broilers to ACS. [ABSTRACT FROM AUTHOR]

Color polymorphism is an ecologically important trait, which is related to local adaptation and ecological speciation. The pea aphid Acyrthosiphon pisum shows color polymorphism: the red and green color morphs where differences in ecological adaptation have been observed. Here, we measured genome-wide gene expression profiles of two color morphs in natural populations of A. pisum to explore the genetic basis of differentiated ecological adaptation. The results showed that only 32 genes were significantly differentially expressed between the two morphs, of which 18 had functional annotations. Among them, 13 genes were up-regulated [e.g. genes encoding protoheme IX farnesyltransferase (LOC100570971), carotene dehydrogenase ( tor ) and V-type proton ATPase subunit B (LOC100169462)] and 5 genes were down-regulated in the red morph (e.g. genes encoding transcription factors and heat shock proteins). To assess the functional importance of these differentially expressed genes (DEGs), we selected three highly expressed DEGs (LOC100169462, LOC100570971 and tor ) with functional annotations and analyzed their expression levels in the red morph under three low temperatures (1 °C, 4 °C, and 8 °C) for 24 h. These three DEGs showed an interesting expression response to the cold acclimating conditions which resulted in an obvious phenotypic change of the red individuals to be greenish variants. This study suggests a link between gene expressions and body color polymorphisms in the pea aphid and provides important clues for further studying molecular mechanisms of ecological adaptation in aphids. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the simultaneous effect of individual and physiological characteristics of subjects on the hands thermal response under severe cold stimulation. So, the hands' transient thermal responses of 89 male students was evaluated by thermography imaging technique. Then, by applying statistical analysis methods, experimental relationships have been developed to estimate the thermal response time of the subjects with different individual and physiological conditions. The results showed that among the 9 individual and physiological parameters (age, vascular fat, muscle percentage, fat percentage, body mass index, systolic blood pressure, diastolic blood pressure, heart rate and fasting time), only there are four independent parameters of internal fat, body mass index, systolic blood pressure and fasting time have a significant relation with the response time. Also, using a multivariate linear regression, a relationship has been developed to estimate the thermal response time of the subjects against cold stimulation. This relationship indicates that the response time of the obese can be up to 20% higher than that of the lean subjects. In addition, the results shows that for each one hour after the last meal, the thermal response of the body is slower about 1%. [ABSTRACT FROM AUTHOR]

To investigate the effect of cold stimulation on heart, 300 1-day-old female broilers were divided into control (CON) and two cold stimulation (CS3 and CS9) groups. Birds in CON group were reared in normal ambient temperature during day 1–43; while birds in CS3 and CS9 groups were reared at 3 °C and 9 °C below CON group for 5 h at 1-day intervals from day 15 to day 35, respectively. Heart tissues were collected at day 22, 29, 36, and 43 to determine the indexes related to oxidative stress, inflammation and apoptosis. The H&E staining displayed that inflammatory cell infiltration and myocardial fiber break were obviously observed in CS9 group, and cardiac pathological score in CS9 group was higher than CON and CS3 groups (P < 0.05) at day 22, 36, and 43. Overall, compared to CON group, the concentrations of MDA and H 2 O 2 were elevated, the activities of SOD, CAT, GPx, and T-AOC were reduced, and mRNA expression of CAT, GPx, SOD, nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) was downregulated in CS9 group at each time-point (P < 0.05). Compared to CON group, mRNA expression of NF-κBp65, COX-2, iNOS, PTGEs, TNF-α, and IL-1β, and mRNA and protein expression of Bax, Bak, Cyt-c, caspase-3, and caspase-9 were increased, while Bcl-2 and Bcl-2/Bax ratio were decreased in CS9 group (P < 0.05) at the most detected time-points. There were no significant differences in the levels of indexes associated with oxidative stress, Nrf2/HO-1 antioxidant system, inflammation, and apoptosis between CON and CS3 groups at the most detected time-points (P > 0.05). Therefore, this study suggests that severe cold stimulation at 9 °C below normal rearing temperature induces cardiomyocyte inflammation and apoptosis by regulating Nrf2/HO-1 pathway-related oxidative stress in broilers, and mild cold stimulation of CS3 group can improve the adaptability of hearts to cold environment. [Display omitted] • Severe cold stimulation induces oxidative stress in broiler heart. • Severe cold stimulation activates NF-κB signaling-mediated inflammation. • Severe cold stimulation causes cardiomyocyte apoptosis. • Mild cold stimulation has no significant adverse effect on broiler heart. [ABSTRACT FROM AUTHOR]

ObjectiveTo use an established biomechanical approach to quantify reflex and non-reflex responses from spastic–paretic elbow flexors in response to controlled cold and heat stimulation.MethodsThirteen spastic–hemiplegic stroke subjects were tested in the experiment. The spastic elbow joint was stretched into extension for 50° at two speeds (5°/s and 100°/s) in a customized apparatus. Thermal stimulation (HEAT at heat pain threshold, COLD at 0°C, or BASELINE at room temperature) was applied to the thenar eminence of the contralateral hand immediately prior to stretching for at least 30 s.ResultsTotal torque was greater at 100°/s than at 5°/s. Total torque was significantly increased after COLD, but not HEAT as compared to BASELINE. When normalized to total torque at baseline, HEAT decreased total torque by 6.3%, while COLD increased total torque by 11.0%. There was no significant difference in the reflex torque among three thermal conditions.ConclusionThe findings demonstrate differentiated effects of cold stimulation on the total resistance from spastic muscles. They provide objective evidence for anecdotal clinical observations of increased muscle spasticity by cold exposure.

Background: Nonallergic vasomotor rhinitis (NAVMR) has been considered a diagnosis by exclusion due to unknown mechanisms or lack of diagnostic biomarkers. Methods: To determine clinical responses and biological pathways in NAVMR subjects challenged to cold dry air (CDA) in an environmental exposure chamber (EEC) pre- and posttreatment with azelastine/fluticasone (AzeFlu), 30 NAVMR subjects, prescreened for CDA-induced symptoms (approx. 14 ° C, <15% relative humidity, ×1 h) were randomized to treatment with AzeFlu ( n = 20) or placebo ( n = 10) for 2 weeks. Total nasal symptoms scores, minimum cross-sectional area, cough, and conjunctival redness were recorded at visit 1 (pretreatment) and visit 2 (posttreatment) before, during, and after CDA challenge. At both visits, nasal lavage fluid (NLF) and nasal scrapings (NS) were collected pre- and post- CDA challenge. Substance P, neurokinin-A, and calcitonin gene-related peptide concentrations in NLF were analyzed pre- and postchallenge at each visit. Their relationship with CDA-induced symptoms was determined by statistical analysis. MicroRNA sequencing from NS determined differentially expressed miRNA between the treatment groups post- CDA challenge at each visit. Results: The minimum crosssectional area ( p < 0.05), cough count ( p < 0.05), and substance P ( p < 0.01) improved posttreatment with AzeFlu versus placebo. Gene targets for differentially expressed miRNAs at visit 1 were enriched for biological pathways regulating epithelial ciliogenesis and cell integrity that were modified in the AzeFlu-treated group versus placebo posttreatment. Conclusions: This study demonstrated the feasibility of an EEC model to investigate CDA-induced clinical responses and pathobiology in NAVMR subjects pre- and posttreatment with AzeFlu. NAVMR disease mechanisms for other nonallergic triggers can be investigated similarly. [ABSTRACT FROM AUTHOR]

This study extends our previous work by examining the effects of alpha2-adrenoceptors under cold stimulation involving the increase of myogenic vascular oscillations as increases of very-low-frequency and low-frequency of the blood pressure variability. Forty-eight adult male Sprague-Dawley rats were randomly divided into four groups: vehicle; yohimbine; hexamethonium+yohimbine; guanethidine+yohimbine. Systolic blood pressure, heart rate, power spectral analysis of spontaneous blood pressure and heart rate variability and spectral coherence at very-low-frequency (0.02 to 0.2 Hz), low-frequency (0.2 to 0.6 Hz), and high-frequency (0.6 to 3.0 Hz) regions were monitored using telemetry. Key findings are as follows: 1) Cooling-induced pressor response was attenuated by yohimbine and further attenuated by hexamethonium+yohimbine and guanethidine+yohimbine, 2) Cooling-induced tachycardia response of yohimbine was attenuated by hexamethonium+yohimbine and guanethidine+yohimbine, 3) Different patterns of power spectrum reaction and coherence value compared hexamethonium+yohimbine and guanethidine+yohimbine to yohimbine alone under cold stimulation. The results suggest that sympathetic activation of the postsynaptic alpha2-adrenoceptors causes vasoconstriction and heightening myogenic vascular oscillations, in turn, may increase blood flow to prevent tissue damage under stressful cooling challenge. [ABSTRACT FROM AUTHOR]

A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists (trans-cinnamaldehyde/L-menthol, respectively), on histamine-induced itch, wheals and neurogenic inflammation in 13 healthy volunteers. Histamine 1% was applied to the volar forearms using skin prick-test lancets. Recorded outcomeparameters were itch intensity, wheal reactions, and neurogenic inflammation (measured by laser-speckle perfusion-imaging). Homotopic thermal counter-irritation was performed with 6 temperatures, ranging from 4°C to 37°C, using a 3 x 3-cm thermal stimulator. Chemical "cold-like" counter-irritation was conducted with 40% L-menthol and 10% trans-cinnamaldehyde, while 5% doxepin was used as a positive antipruritic control/comparator. Cold counter-irritation stimuli from 4°C to 22°C inhibited itch in a stimulus-intensitydependent manner (p < 0.05) and, to a lesser extent, also wheal reactions and neurogenic inflammation. Chemical "cold-like" counter-irritation with both Lmenthol and trans-cinnamaldehyde had antipruritic efficacy similar to doxepin (p < 0.05). Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value. [ABSTRACT FROM AUTHOR]

Phalangeal microgeodic syndrome is a rare but benign disorder that affects the fingers of children. Ultrasonographic imaging was performed on an 11-year-old female presenting with a 3-week history of pain and swelling in the fourth and fifth right-hand fingers. Small bone erosions on the middle phalanx of swollen fingers were detected in the gray scale image, and increased blood flow signal was found in the bone erosion area and soft tissue with power Doppler. Ultrasonography is more convenient and less expensive than imaging modalities such as magnetic resonance imaging. Ultrasonography has utility in diagnosis of phalangeal microgeodic syndrome. [ABSTRACT FROM AUTHOR]