Cold Stimulation Research Articles

‘’Brown adipose tissue in the form of innovative approach for polycystic ovary syndrome treatment-still long time to reach clinical arena: a narrative review’’

Brown adipose tissue(BAT)portrays a specialized tissue, possessing a crucial part in metabolism as well as energy expenditure(EE) via adaptive non shivering thermogenesis .Recently it has assumed a significant part in the treatment of obesity along with metabolic disease.The thermogenesis action of BAT is brought about by uncoupling protein1 (UCP1 ),that uncouples adenosine triphosphate (ATP) generation from oxidation of energy substrates.Having reviewed earlier various aspects pf Polycystic ovary syndrome (PCOS) pathophysiology,treatment,role in trans generational PCOS transferalong with role of BAT pathophysiology,beige/brite adipocytes in the treatment of obesity along with metabolic disease here we decided to further evaluate the possible part of BAT in PCOS. Thus anarrative review was carried out using the pubmed, Web of Science , Medline, Embase, Cochrane reviews, and Google Scholar, Search engine with the MeSH Terms;PCOS; impaired lipid metabolism; Brown Adipose tissue (BAT); White Adipose tissue(WAT); oxidative stress;inflammation;obesity ;T2DM); Type 1 diabetes (T1D); role of natural substances for PCOStherapy like rutin ,berberine;resveratrol ; weight reduction; browning of WAT ;Macrophage Polarization from 1990 till date in 2023.We found a total of 250 articles ,out of which we selected. 100 articles for this review. No meta-analysis was done. The endocrine action of brown Adipocytes impacts the energy balanceof glucose as well as lipid homeostasis thus impacting the correlation of BAT activity along with metabolic profile. PCOS mirrors a complicated reproductive as well asmetabolic condition of women in their reproductive age. Fcapital aberrations in adipose tissue have been illustrated in PCOS patients. Multiple studies have illustrated that BAT possesses the capacity of controlling the properties of PCOS as well as escalating BAT mass/activity were efficacious in the therapy of PCOS. Via cold stimulation, BAT transplantation as well as activationwith substances like rutin aypoglycemiaX along with as well as

Intermittent mild cold stimulation alleviates cold stress-induced pulmonary fibrosis by inhibiting the TGF-β1/Smad signaling pathway in broilers

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.

CXCL13 promotes thermogenesis in mice via recruitment of M2 macrophage and inhibition of inflammation in brown adipose tissue.

Brown adipose tissue (BAT) is mainly responsible for mammalian non-shivering thermogenesis and promotes energy expenditure. Meanwhile, similar to white adipose tissue (WAT), BAT also secretes a variety of adipokines to regulate metabolism through paracrine, autocrine, or endocrine ways. The chemokine C-X-C motif chemokine ligand-13 (CXCL13), a canonical B cell chemokine, functions in inflammation and tumor-related diseases. However, the role of CXCL13 in the adipose tissues is unclear. The expression of CXCL13 in BAT and subcutaneous white adipose tissue (SWAT) of mice under cold stimulation were detected. Local injection of CXCL13 into BAT of normal-diet and high-fat-diet induced obese mice was used to detect thermogenesis and determine cold tolerance. The brown adipocytes were treated with CXCL13 alone or in the presence of macrophages to determine the effects of CXCL13 on thermogenic and inflammation related genes expression in vitro. In this study, we discovered that the expression of CXCL13 in the stromal cells of brown adipose tissue significantly elevated under cold stimulation. Overexpression of CXCL13 in the BAT via local injection could increase energy expenditure and promote thermogenesis in obese mice. Mechanically, CXCL13 could promote thermogenesis via recruiting M2 macrophages in the BAT and, in the meantime, inhibiting pro-inflammatory factor TNFα level. This study revealed the novel role of adipose chemokine CXCL13 in the regulation of BAT activity and thermogenesis.

Intermittent cold stimulation affects energy metabolism and improves stress resistance in broiler heart

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.

Towards a central origin of nociceptive hypersensitivity in adult rats after a neonatal maternal separation.

Early life adversities influence a nervous system still in development with long-term consequences for later life. These include nociceptive circuit alterations critical to shape an adaptive pain response to protect the organism from potential damage. Adult rats with a history of neonatal maternal separation (NMS) display visceral and somatic nociceptive hypersensitivity and inefficient analgesic responses to stress. In this study, we have characterized the consequences of NMS on wide dynamic range neurons (WDR) in the spinal cord of anaesthetized adult rats during the nociceptive processing of hot and cold noxious information. We found that WDR neurons of NMS rats display an excessive coding of mechanical and thermal information applied at the rat's hindpaws. This nicely explains the hypernociceptive behaviours seen after noxious mechanical, cold and hot peripheral stimulation. A peripheral change in the expression of molecular transducers for these stimuli (i.e., TRPV1, TRPM8 and TRPA1) does not seem to account for this general hyperexcitability. Instead, a decreased chloride-mediated inhibitory tone on WDR neurons may play a role as indicated by the abnormal elevation of the type 1 Na-K-Cl cotransporter transcripts. Altogether, we propose that long-term consequences of NMS are associated with reduced spinal cord inhibition favouring the expression of pain hypersensitivity. We cannot exclude that this phenomenon is also present at supraspinal sites, as other NMS-associated symptoms include excessive anxiety and impaired sociability.

FAM210A is essential for cold-induced mitochondrial remodeling in brown adipocytes

Cold stimulation dynamically remodels mitochondria in brown adipose tissue (BAT) to facilitate non-shivering thermogenesis in mammals, but what regulates mitochondrial plasticity is poorly understood. Comparing mitochondrial proteomes in response to cold revealed FAM210A as a cold-inducible mitochondrial inner membrane protein. An adipocyte-specific constitutive knockout of Fam210a (Fam210aAKO) disrupts mitochondrial cristae structure and diminishes the thermogenic activity of BAT, rendering the Fam210aAKO mice vulnerable to lethal hypothermia under acute cold exposure. Induced knockout of Fam210a in adult adipocytes (Fam210aiAKO) does not affect steady-state mitochondrial structure under thermoneutrality, but impairs cold-induced mitochondrial remodeling, leading to progressive loss of cristae and reduction of mitochondrial density. Proteomics reveals an association between FAM210A and OPA1, whose cleavage governs cristae dynamics and mitochondrial remodeling. Mechanistically, FAM210A interacts with mitochondrial protease YME1L and modulates its activity toward OMA1 and OPA1 cleavage. These data establish FAM210A as a key regulator of mitochondrial cristae remodeling in BAT and shed light on the mechanism underlying mitochondrial plasticity in response to cold.

Skin Cold Stimulation Can Modulate the Perceptual Rating of Musical Chords.

We studied the effect of cutaneous cold stimulus on the perceptual rating of musical chords. Despite the shown influence of music and tactile stimuli on human psychological evaluation, the effect of a cold stimulus on sound perception remains underexplored. We examined the effect of a cold stimulus on four psychological measures (frisson, arousal, pleasantness, and valence) as participants listened to two-note chords (consonance and dissonance). The cold-stimulus condition involved an experimenter touching the back of the participant's neck with a cooling device while listening to the sounds, while the control condition used a cooling device with the power off. For the frisson and arousal measures, the main effect of the stimulus condition was significant, showing that the cold stimulus increased the frisson and arousal measures. For the pleasantness and valence measures, there was a significant main effect of two-note chords, showing that a consonance was perceived as more pleasant than a dissonance; however, there was no significant main effect of stimulus condition, showing that the cold stimulus did not affect pleasantness and valence ratings. The results showed that a cold stimulus could bias frisson and arousal without affecting pleasantness and valence ratings when listening to musical sound.

Effect of gut microbiota homeostasis on hematopoiesis in a neonatal rat model of necrotizing enterocolitis

To study the effect of gut microbiota on hematopoiesis in a neonatal rat model of necrotizing enterocolitis (NEC). Neonatal Sprague-Dawley rats were randomly divided into a control group and a model group (NEC group), with 6 rats in each group. Formula milk combined with hypoxia and cold stimulation was used to establish a neonatal rat model of NEC. Hematoxylin and eosin staining was used to observe the pathological changes of intestinal tissue and hematopoiesis-related organs. Routine blood tests were conducted for each group. Immunohistochemistry was used to observe the changes in specific cells in hematopoiesis-related organs. Flow cytometry was used to measure the changes in specific cells in bone marrow. 16S rDNA sequencing was used to observe the composition and abundance of gut microbiota. Compared with the control group, the NEC group had intestinal congestion and necrosis, damage, atrophy, and shedding of intestinal villi, and a significant increase in NEC histological score. Compared with the control group, the NEC group had significantly lower numbers of peripheral blood leukocytes and lymphocytes (P<0.05), nucleated cells in the spleen, thymus, and bone marrow, and small cell aggregates with basophilic nuclei in the liver (P<0.05). The NEC group had significant reductions in CD71+ erythroid progenitor cells in the liver, CD45+ lymphocytes in the spleen and bone marrow, CD3+ T lymphocytes in thymus, and the proportion of CD45+CD3-CD43+SSChi neutrophils in bone marrow (P<0.05). There was a significant difference in the composition of gut microbiota between the NEC and control groups, and the NEC group had a significant reduction in the abundance of Ligilactobacillus and a significant increase in the abundance of Escherichia-Shigella (P<0.05), which replaced Ligilactobacillus and became the dominant flora. Multi-lineage hematopoietic disorder may be observed in a neonatal rat model of NEC, which may be associated with gut microbiota dysbiosis and abnormal multiplication of the pathogenic bacteria Escherichia-Shigella.

The Contribution of TRPA1 to Corneal Thermosensitivity and Blink Regulation in Young and Aged Mice.

The role of TRPA1 in the thermosensitivity of the corneal cold thermoreceptor nerve endings was studied in young and aged mice. The contribution of the TRPA1-dependent activity to basal tearing and thermally-evoked blink was also explored. The corneal cold thermoreceptors' activity was recorded extracellularly in young (5-month-old) and aged (18-month-old) C57BL/6WT (WT) and TRPA1-/- knockout (TRPA1-KO) mice at basal temperature (34 °C) and during cooling (15 °C) and heating (45 °C) ramps. The blink response to cold and heat stimulation of the ocular surface and the basal tearing rate were also measured in young animals using orbicularis oculi muscle electromyography (OOemg) and phenol red threads, respectively. The background activity at 34 °C and the cooling- and heating-evoked responses of the cold thermoreceptors were similar in WT and TRPA1-KO animals, no matter the age. Similar to the aged WT mice, in the young and aged TRPA1-KO mice, most of the cold thermoreceptors presented low frequency background activity, a low cooling threshold, and a sluggish response to heating. The amplitude and duration of the OOemg signals correlated with the magnitude of the induced thermal change in the WT but not in the TRPA1-KO mice. The basal tearing was similar in the TRPA1-KO and WT mice. The electrophysiological data suggest that the TRPA1-dependent nerve activity, which declines with age, contributes to detecting the warming of the ocular surface and also to integrating the thermally-evoked reflex blink.

Preliminary study of finger temperature recovery in patients with diabetes mellitus following cold stimulation.

To explore the difference in temperature recovery following cold stimulation between participants with and without diabetes mellitus (DM). The participants without (control group; n=25) and with (DM group; n=26) DM were subjected to local cold stimulation (10º C for 90s). The thermal images of their hands were continuously captured using a thermal camera within 7min 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. 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. 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.

Brown adipose tissue in the form of innovative approach for polycystic ovary syndrome treatmentstill long time to reach clinical arena: a narrative review

Brown adipose tissue(BAT)portrays a specialized tissue, possessing a crucial part in metabolism as well as energy expenditure(EE) via adaptive non shivering thermogenesis .Recently it has assumed a significant part in the treatment of obesity along with metabolic disease.The thermogenesis action of BAT is brought about by uncoupling protein1 (UCP1 ),that uncouples adenosine triphosphate (ATP) generation from oxidation of energy substrates.Having reviewed earlier various aspects of Polycystic ovary syndrome (PCOS) pathophysiology,treatment,role in trans generational PCOS transferalong with role of BAT pathophysiology,beige/brite adipocytes in the treatment of obesity along with metabolic disease here we decided to further evaluate the possible part of (BAT in PCOS. Thus anarrative review was carried out using the pubmed, Web of Science , Medline, Embase, Cochrane reviews, and Google Scholar, Search engine with the MeSH Terms;PCOS; impaired lipid metabolism; Brown Adipose tissue (BAT); White Adipose tissue(WAT); oxidative stress;inflammation;obesity ;T2DM); Type 1 diabetes (T1D); role of natural substances for PCOStherapy like rutin ,berberine;resveratrol ; weight reduction; browning of WAT ;Macrophage Polarization from 1990 till date in 2023.We found a total of 250 articles ,out of which we selected 100 articles for this review.No meta-analysis was done.The endocrine action of brown Adipocytes impacts the energy balanceof glucose as well as lipid homeostasis thus impacting the correlation of BAT activity along with metabolic profile . PCOS mirrors a , complicated reproductive as well asmetabolic condition of women in their reproductive age . functional aberrations in adipose tissue have been illustrated in PCOS patients .Multiple studies have illustrated that BAT possesses the capacity of controlling the properties of PCOS as well as escalating BAT mass/activity were efficacious in the therapy of PCOS. Via cold stimulation,BAT transplantation as well as activationwith substances like rutin hypoglycemia can be attained.

Comparison of Cerebral Blood Volume during Cold and Warm Stimulation in Elderly and Young Subjects.

Dementia involves a neuronal loss in the primary somatosensory cortex of the parietal lobe, causing dementia patients to perceive pain stimuli hardly. The function of temperature sensation declines. Studies measuring brain blood volume using near-infrared light have reported that patients suffering from dementia have less activation than healthy elderly people. However, the majority of these studies used tests related to cognitive function and the frontal lobe, and few have examined thermal sensation. The present study aimed to investigate the effect of cold and warm stimulation on cerebral blood volume in elderly and young subjects. This observational study measured changes in oxygenated hemoglobin concentrations in the frontal cortex during cold and warm stimulation in elderly and young subjects using a near-infrared light device. The mean and standard deviation of the change in oxygenated hemoglobin concentration before and after cold and warm stimulation, as well as the center-of-gravity values, were compared between the young and the elderly. During warm stimulation, the younger subjects showed an increase in blood oxygenated hemoglobin levels; however, the difference was not significant. For the elderly, no change was observed during the task. The center of gravity values was lower in the young compared to the elderly which was similar to the reaction threshold. No significant changes were observed during cold stimulation. Thermal sensation thresholds were impaired in the elderly compared to the young; however, cerebral blood volume changes were unclear.

The effects of cold stimulation and exercise on human health

Abstract Cold stimulation and exercise are two independent stimulus variables, each yielding unique impacts on human health. However, in many cases, individuals often encounter both factors simultaneously, particularly in colder regions where outdoor physical activity is prevalent. Despite numerous studies exploring the effects of cold exposure and exercise independently, only a limited number of comprehensive reviews have evaluated their combined influence on health. This review aims to bridge this gap by meticulously examining the potential benefits and detriments of both cold stimulation and exercise on human health. Specifically, the review focuses on their impacts on cardiovascular, respiratory, and immune function, as well as the favorable effects of moderate exercise on the human body. While evidence suggests that cold exposure can enhance health outcomes in certain disease contexts, it also poses risks, particularly for vulnerable populations. Furthermore, while moderate exercise is generally beneficial, engaging in physical activity in cold weather conditions can increase the risk of hypothermia, frostbite, and other cold-related injuries. Consequently, there is an urgent need to develop safe and effective guidelines for exercising in cold weather, particularly for individuals living in colder regions. This review emphasizes the necessity for further research on the combined effects of cold stimulation and exercise, with the goal of informing public health policies and guidelines for physical activity in cold weather conditions.

Anesthetic Spread of Ultrasound-Guided Paraspinal Blocks in Video-Assisted Thoracoscopic Surgery: A Three-Dimensional Reconstruction Image Study

BACKGROUND: Anesthetic spread of ultrasound-guided paraspinal blocks is still unknown. OBJECTIVES: To compare the drug diffusion qualities of intertransverse process block (ITPB) and erector spinae plane block (ESPB) in clinical practice. STUDY DESIGN: Prospective computed tomography (CT)-3-dimensional (3D) reconstruction image study. SETTING: Operation room in hospital. METHODS: Twenty patients undergoing thoracoscopic pulmonary wedge resection or segmentectomy were enrolled. These procedures require localization of pulmonary nodules using CT-guided needle puncture immediately before surgery. The patients were divided into 2 groups, each consisting of 10 patients. Group I underwent ITPB, while group E underwent ESPB. These interventions were performed 30 minutes before surgery using 20 mL of 0.25% bupivacaine with 2 mL iohexol. Sensory loss of the thoracic dermatomes was assessed using cold stimulation before general anesthesia. Patients’ CT localization images were used for 3D reconstruction after surgery, and the diffusion of the drug in each cross-section of the CT images was evaluated. RESULTS: Three-dimensional imaging of the drug showed that in group E, drug diffusion was improved in the cephalocaudal area compared to group I (10 vs 4.5 segments). Drug diffusion in group I was improved anteriorly and laterally ([10/10, 100%] in the paravertebral and intercostal spaces) and reached the front of the vertebral body along the thoracic fascia in certain segments (6/10, 60%). In group E, very few segments of the drug reached the paravertebral (2/10, 20%) and intercostal (3/10, 30%) spaces. All patients in group I had clear signs of loss of cold sensation on the lateral and anterior chest walls, with an average of 4 thoracic dermatomes. In group E, 3 patients had definite lateral and anterior chest wall cold stimulation signs, the thoracic dermatome was discontinuous, and the effect was only present between 1-2 segments. The blocking effect of the paraspinal zone was excellent (100%) in both groups. LIMITATIONS: However, this study has some limitations. First, the sample size was small, and clinical trials with larger samples are required to further verify the effects of ITPB and ESPB. Second, the same local anesthetic drug concentration and volume were used for both techniques in this study, and the effect of volume or concentration on drug diffusion was not further explored. CONCLUSIONS: Compared with ESPB, ITPB yielded increased stability in lateral and anterior chest wall block with improved anterior and intercostal spread, but reduced cephalocaudal spread. KEY WORDS: Erector spinae plane block, intertransverse process block, 3-dimensional imaging, paraspinal block, drug diffusion, video-assisted, thoracoscopic surgery, 3D reconstruction

Topical Oxaliplatin Produces Gain- and Loss-of-Function in Multiple Classes of Sensory Afferents

The platinum chemotherapeutic oxaliplatin produces dose-limiting pain, dysesthesia, and cold hypersensitivity in most patients immediately after infusion. An improved understanding of the mechanisms underlying these symptoms is urgently required to facilitate the development of symptomatic or preventative therapies. In this study, we have used skin-saphenous nerve recordings in vitro and behavioral experiments in mice to characterize the direct effects of oxaliplatin on different types of sensory afferent fibers. Our results confirmed that mice injected with oxaliplatin rapidly develop mechanical and cold hypersensitivities. We further noted profound changes to A fiber activity after the application of oxaliplatin to the receptive fields in the skin. Most oxaliplatin-treated Aδ- and rapidly adapting Aβ-units lost mechanical sensitivity, but units that retained responsiveness additionally displayed a novel, aberrant cold sensitivity. Slowly adapting Aβ-units did not display mechanical tachyphylaxis, and a subset of these fibers was sensitized to mechanical and cold stimulation after oxaliplatin treatment. C fiber afferents were less affected by acute applications of oxaliplatin, but a subset gained cold sensitivity. Taken together, our findings suggest that direct effects on peripheral A fibers play a dominant role in the development of acute oxaliplatin-induced cold hypersensitivity, numbness, and dysesthesia. PerspectiveThe chemotherapeutic drug oxaliplatin rapidly gives rise to dose-limiting cold pain and dysesthesia. Here, we have used behavioral and electrophysiological studies of mice to characterize the responsible neurons. We show that oxaliplatin directly confers aberrant cold responsiveness to subsets of A-fibers while silencing other fibers of the same type.

Modern and Non-Invasive Methods of Fat Removal.

Adipocytes accumulate triacylglycerols as an energy store, thereby causing an increase in the adipose tissue volume. Weight gain can be prevented through damage to the adipocyte structure or an increase in the body's metabolic rate. Commonly used methods to disintegrate the cell membrane of adipocytes include injection lipolysis, cryolipolysis, ultrasonic lipolysis, radiofrequency lipolysis, laser lipolysis, carboxytherapy, and lipolysis using an electromagnetic field. The names of these methods suggest which substances are being used, and their main advantages are a very low invasiveness, as well as effectiveness. However, new discoveries in medicine, along with individuals' desire to improve their appearance, have resulted in numerous studies on more ways of reducing body fat. Great potential is seen in beige adipocytes, which can be transformed, i.e., "recruited" from white adipocytes, or synthesized de novo; they also show thermogenic properties. One of the stimuli inducing the formation of beige adipocytes is cold and B3-adrenergic stimulation. Based on these findings, the researchers created, for example, cooling clothing. Additionally, curcumin and natural anthocyanins have proven to be helpful in the treatment of obesity and diabetes, by stimulating the secretion of glucagon-like peptide-1, and inducing the formation of beige adipocytes. Another study showed that the conversion of white adipose tissue is indirectly influenced by interleukin-6 secreted by the muscles, the expression of which is increased in people actively exercising. Moreover, there is potential in adenosine analogs, fenoldopam, rhubarb, the herbal extract Ephedra sinica Stapf, electroacupuncture simulation, and the drug CBL-514. Despite knowledge and experience, the ideal method for a quick and noticeable, but safe and non-invasive reduction of body fat has not been found yet. The research conducted nowadays may bring us closer to the development of a universal method, and turn out to be a breakthrough in the fight against overweight and obesity.

Cold stimulation causes oxidative stress, inflammatory response and apoptosis in broiler heart via regulating Nrf2/HO-1 and NF-κB pathway

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 H2O2 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.

The First Discovery of a Microstructure in Black Plaster and Its Performance Characterization.

Black plaster is one of the classic dosage forms of traditional Chinese medicine for external use and has been widely utilized since the Tang and Song Dynasties. In this paper, we take Goupi Gao as the research object and discuss the scientific characteristics of the black plaster dosage form. Goupi Gao ointment is a plaster for external use of traditional Chinese medicine. Methods for the morphological and quantitative characterization of black plaster's microstructure, based on FESEM-IPP (Field Emission Scanning Electron Microscope IPP Image Processing) technology, were established. According to the actual operating temperature of Goupi Gao, three temperatures were selected: 28°C, 35°C, and 45°C. A UPLC analysis method was applied to the cinnamaldehyde and eugenol in Goupi Gao, and the release behavior of Goupi Gao from three samples at three temperatures was investigated using the paddle over disk method. Preparation of rabbit model of knee osteoarthritis of cold blood stasis type by cold stimulation combined with drug induction. In terms of morphology, Goupi Gao and the blank black plaster matrix both formed a double continuous phase system with a thicker vegetable oil phase and crossed "branched" soap crystal fibers. Based on the IPP image quantification parameters, the pore area (A) was highly positively correlated with temperature. After the 28 °C treatment, A1 = (216.8±59.5) μm2; after the 35 °C treatment, A2 = (259.7±52.8) μm2; after the 45 °C treatment, A3 = (408.0±57.7) μm2, and there were no significant differences in other pore parameters. The black plaster matrix's unique structure makes it highly applicable in numerous medications; it exhibits slow-release and performs well in extreme temperatures, with good adhesion and peeling properties.

NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis

BackgroundMacrophages are involved in various immune inflammatory disease conditions. This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis (NEC).MethodsCD68, nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3), cysteine aspartate-specific protease-1 (caspase-1), and interleukin-1β (IL-1β) in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry, immunofluorescence, and western blot. Hypertonic pet milk, hypoxia and cold stimulation were used to establish a mouse (wild type and Nlrp3−/−) model of NEC. The mouse macrophage (RAW 264.7) and rat intestinal epithelial cell-6 lines were also cultured followed by various treatments. Macrophages, intestinal epithelial cell injuries, and IL-1β release were determined.ResultsCompared to the gut “healthy” patients, the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3, caspase-1, and IL-1β levels. Furthermore, in vivo, the survival rate of Nlrp3−/− NEC mice was dramatically improved, the proportion of intestinal macrophages was reduced, and intestinal injury was decreased compared to those of wild-type NEC mice. NLRP3, caspase-1, and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell injuries.ConclusionsMacrophage activation may be essential for NEC development. NLRP3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development, and all these may be therapeutic targets for developing treatments for NEC.

Intermittent and Mild Cold Stimulation Maintains Immune Function Stability through Increasing the Levels of Intestinal Barrier Genes of Broilers.

In order to improve the adaptability of broilers to low-temperature environments and their ability to resist acute cold stress (ACS), 240 one-day-old broilers were selected and randomly divided into three groups. The control treatment (CC) group was raised at the conventional feeding temperature from 1-43 days (d), the cold stimulation treatment (CS) group was kept at 3 °C below the temperature of CC at 1 d intervals for 3 and 6 h from 15 to 35 d, namely, CS3 and CS6, respectively. Then, all broilers were kept at 20 °C from 36 to 43 d. ACS was then carried out at 44 d, and the ambient temperature was dropped to 10 °C for 6 h. The study investigated the production performance, as well as levels of intestinal barrier genes (including Claudin-1, E-cadherin, Occludin, ZO-1, ZO-2 and Mucin2), secretory IgA in duodenum and jejunum, and immunoglobulins (IgA and IgG) in serum. The results showed that IMCS could increase the daily weight gain and decrease the feed conversion ratio. During IMCS, the expression levels of intestinal barrier genes were up-regulated and the content of secretory IgA was increased. When IMCS ceased for one week, the level of immunoglobulins in serum stabilized, and the expression levels of Occludin, ZO-2 and Mucin2 still maintained high levels. After ACS, broilers that received IMCS training maintained high levels of intestinal barrier genes and secretory IgA.