Nausea-induced suppression of feeding is mediated by central amygdala Dlk1-expressing neurons.

The motivation to eat is suppressed by satiety and aversive stimuli such as nausea. The neural circuit mechanisms of appetite suppression by nausea are not well understood. Pkcδ neurons in the lateral subdivision of the central amygdala (CeA) suppress feeding in response to satiety signals and nausea. Here, we characterized neurons enriched in the medial subdivision (CeM) of the CeA marked by expression of Dlk1. CeADlk1 neurons are activated by nausea, but not satiety, and specifically suppress feeding induced by nausea. Artificial activation of CeADlk1 neurons suppresses drinking and social interactions, suggesting a broader function in attenuating motivational behavior. CeADlk1 neurons form projections to many brain regions and exert their anorexigenic activity by inhibition of neurons of the parabrachial nucleus. CeADlk1 neurons are inhibited by appetitive CeA neurons, but also receive long-range monosynaptic inputs from multiple brain regions. Our results illustrate a CeA circuit that regulates nausea-induced feeding suppression.

Pharmacological and mechanistic aspects of quercetin in osteoporosis.

Osteoporosis (OP) is a bone disease associated with increasing age. Currently, the most common medications used to treat OP are anabolic agents, anti-resorptive agents, and medications with other mechanisms of action. However, many of these medications have unfavorable adverse effects or are not intended for long-term use, potentially exerting a severe negative impact on a patient's life and career and placing a heavy burden on families and society. There is an urgent need to find new drugs that can replace these and have fewer adverse effects. Quercetin (Que) is a common flavonol in nature. Numerous studies have examined the therapeutic applications of Que. However, a comprehensive review of the anti-osteoporotic effects of Que has not yet been conducted. This review aimed to describe the recent studies on the anti-osteoporotic effects of Que, including its biological, pharmacological, pharmacokinetic, and toxicological properties. The outcomes demonstrated that Que could enhance OP by increasing osteoblast differentiation and activity and reducing osteoclast differentiation and activity via the pathways of Wnt/ß-catenin, BMP/SMAD/RUNX2, OPG/RANKL/RANK, ERK/JNK, oxidative stress, apoptosis, and transcription factors. Thus, Que is a promising novel drug for the treatment of OP.

Ultrasensitive Eu-Based MOF Luminescence Sensor for Clenbuterol Visible Recognition.

Clenbuterol (CLB) as an illegal feed additive may cause a great security risk to food safety. However, convenient and efficient detection means for CLB in practical application remain a formidable challenge. Herein, a stable Eu-based organic framework {[H2N(CH3)2]2[Eu2(ttca)2]·H2O}n (compound 1) (H4ttca = [1,1':2',1″-terphenyl]-4,4',4″,5'-tetracarboxylic acid) has been harvested, exhibiting excellent chemical stability and thermal stability. Luminescence investigation reveals that compound 1 can sensitively and selectively detect CLB without being affected by different components from simulated serum and urine (limit detection: 22.7 nM). Furthermore, sensor 1 can also be applicable to CLB recognition in real swine feeds, presenting excellent anti-interference performance. The good cyclicity of compound 1 endows CLB determination with many advantages: low cost, high stability, and simplicity. Importantly, in view of the indication of the luminescence color (red to blue), test membranes were fabricated and employed for convenient and fast CLB detection, providing a valuable scheme for the visual monitoring of CLB in meat products. This work enriches rare earth metal compounds and luminescence sensor portfolios and breaks the concentration record (nM) for detecting CLB compared with reported complex materials, providing an effective monitoring platform for CLB visually.

Lipidomics-based analysis of lipid differences between dry skin of women aged 22-28 years and 29-35 years.

BACKGROUND: The skin condition of women is different at different ages, and skin surface lipids are also different. According to the "7-7 theory" of the Huangdi Neijing, the physiological condition of women changes significantly every 7 years, and women aged 22-28 are in the "4-7" stage as mentioned in the "7-7 theory" of the Huangdi Neijing. Women's skin is in different states at different ages and produces different lipids. OBJECTIVES: To explore the key lipids that contribute to skin differences between women aged 22-28 and 29-35 years, and to explore the relationship with physiological parameters and daily routine. METHODS: Differential lipids were detected and screened between 22-28 year old (group D1) and 29-35 year old (group D2) dry-skinned women using UPLC-Q-TOF-MS and correlated between the two groups with questionnaires and physiological parameters based on basic information, lifestyle habits, work situation, and emotional stress. RESULTS: The results showed that all of the eight major classes of lipids had the highest expression in the D2 group, with the largest differences in glycerophospholipids, glycerol esters, and fatty acids. The BMI value of D2 group was higher than that of D1 group, the skin elasticity index (R2) and brightness index (L, a, ITA values) were lower than that of D1 group, and Cer (d18:0/16:0) was positively correlated with the R2, L, a, and ITA, and LMSP01080056 (N,N-dimethyl-Safingol) was positively correlated with the b-value, the LMSPGP03020013, LMSPGP03020014, LMSP03020024 were significantly negatively correlated with R2. CONCLUSIONS: Cer(d18:0/16:0) is a neurosphingol that inhibits elastase expression. N,N-dimethyl-Safingol readily undergoes oxidation to form yellow-brown solids. The macromolecular structure and excessive carbonyl structure of [LMGP0302] are susceptible to cross-linking and carbonyl stress reactions, which accelerate skin aging and reduce skin elasticity, and thus, they may be key lipids contributing to skin differences between the two age groups.

Decoding the spatiotemporal regulation of transcription factors during human spinal cord development.

The spinal cord is a crucial component of the central nervous system that facilitates sensory processing and motor performance. Despite its importance, the spatiotemporal codes underlying human spinal cord development have remained elusive. In this study, we have introduced an image-based single-cell transcription factor (TF) expression decoding spatial transcriptome method (TF-seqFISH) to investigate the spatial expression and regulation of TFs during human spinal cord development. By combining spatial transcriptomic data from TF-seqFISH and single-cell RNA-sequencing data, we uncovered the spatial distribution of neural progenitor cells characterized by combinatorial TFs along the dorsoventral axis, as well as the molecular and spatial features governing neuronal generation, migration, and differentiation along the mediolateral axis. Notably, we observed a sandwich-like organization of excitatory and inhibitory interneurons transiently appearing in the dorsal horns of the developing human spinal cord. In addition, we integrated data from 10× Visium to identify early and late waves of neurogenesis in the dorsal horn, revealing the formation of laminas in the dorsal horns. Our study also illuminated the spatial differences and molecular cues underlying motor neuron (MN) diversification, and the enrichment of Amyotrophic Lateral Sclerosis (ALS) risk genes in MNs and microglia. Interestingly, we detected disease-associated microglia (DAM)-like microglia groups in the developing human spinal cord, which are predicted to be vulnerable to ALS and engaged in the TYROBP causal network and response to unfolded proteins. These findings provide spatiotemporal transcriptomic resources on the developing human spinal cord and potential strategies for spinal cord injury repair and ALS treatment.

Role of anthraquinones in combating insulin resistance.

Insulin resistance presents a formidable public health challenge that is intricately linked to the onset and progression of various chronic ailments, including diabetes, cardiovascular disease, hypertension, metabolic syndrome, nonalcoholic fatty liver disease, and cancer. Effectively addressing insulin resistance is paramount in preventing and managing these metabolic disorders. Natural herbal remedies show promise in combating insulin resistance, with anthraquinone extracts garnering attention for their role in enhancing insulin sensitivity and treating diabetes. Anthraquinones are believed to ameliorate insulin resistance through diverse pathways, encompassing activation of the AMP-activated protein kinase (AMPK) signaling pathway, restoration of insulin signal transduction, attenuation of inflammatory pathways, and modulation of gut microbiota. This comprehensive review aims to consolidate the potential anthraquinone compounds that exert beneficial effects on insulin resistance, elucidating the underlying mechanisms responsible for their therapeutic impact. The evidence discussed in this review points toward the potential utilization of anthraquinones as a promising therapeutic strategy to combat insulin resistance and its associated metabolic diseases.

Prediction of Nanoscale Water Meniscus Shape between Deliquescent KDP Crystal Optics and AFM Probe for Water-Dissolution Repairing.

KDP (KH2PO4) crystal optics are the key elements for megajoule laser facilities. Nanoscale surface defects would cause laser-induced damage when the optics are irradiated by a high-fluence laser (over 10 J/cm2). Dip-pen nanolithography (DPN) could be used to repair the nanoscale surface defects in the KDP optics by the water meniscus. The high humidity required for high-efficiency and soft KDP surfaces penetrated by the AFM probe brings challenges for accurately predicting the water meniscus shape to evaluate the effectiveness of the DPN water-dissolution repairing. The multisolutions of the Young-Laplace and Kelvin equations also lead to the wrong water meniscus shape. A theoretical model that takes the high humidity and the penetration of the AFM probes into account is developed. The parametrization Young-Laplace equations are adopted for the zero contact angle of the water films, and the AFM probe is treated as the combination of the cone and sphere for the water meniscus whose size is larger than the AFM tip radius under high humidity. The penetration of the AFM probe is modeled by Hertz theory. Both the water films (3.3 nm thickness at 99% relative humidity) and indentations (1.46 nm depth at 300 nN contact force) are non-negligible for the nanoscale water meniscus between the KDP surface and the AFM probe. Moreover, the rough-fine two-step method is proposed to lock the correct solution of the Young-Laplace and Kelvin equations. The effectiveness of the proposed model is verified by comparison with reported ESEM images and pull-off forces. In addition, the overgrowth dots on the KDP surface are compared with the water meniscus. The linear growth of the water meniscus would cause the linear growth of the overgrowth dot, which proves the proposed model could be used to guide the DPN water-dissolution repairing for the nanoscale surface defects in the KDP optics.

Circulating Concentrations of advanced Glycation end Products, Carboxymethyl Lysine and Methylglyoxal are Associated With Renal Function in Individuals With Diabetes.

OBJECTIVE: Diabetic kidney disease (DKD) is one of the most severe chronic complications of diabetes and is associated with higher level of advanced glycation end products (AGEs). The aim of this study was to investigate the diagnostic potential of combined detection of multiple serum AGEs in diagnosing DKD. METHODS: Serum AGEs, Nε-(carboxymethyl) lysine (CML), Nε-(carboxyethyl) lysine, and methylglyoxal (MGO) levels were measured by enzyme-linked immunosorbent assay in 176 individuals with type 2 diabetes. Participants were classified into normoalbuminuria, microalbuminuria, and macroalbuminuria group according to their urinary albumin to creatinine ratio (UACR). RESULTS: Higher serum AGEs levels were found to be positively correlated with U-Alb, UACR, and blood urea nitrogen in the study of 176 individuals with type 2 diabetes. CML and MGO levels were positively correlated with U-Alb, UACR, blood urea nitrogen, Scr, and uric acid, and negatively correlated with estimated glomerular filtration rate (P < .05). Multivariate logistic regression analysis showed that elevated levels of AGEs, CML, and MGO were independent risk factors for the progression of DKD (odds ratio = 1.861, 1.016, 7.607, P < .01). The sensitivity, specificity, and area under receiver operating characteristic curve of combined detection of AGEs, MGO, and CML were higher than those of three individual detections (area under the curve = 0.952, 0.772, 0.868, 0905, respectively, P < .05). CONCLUSION: The combined detection of AGEs, CML, and MGO may improve the reliability of early diagnosis of DKD.

Oral administration of kynurenic acid delays the onset of type 2 diabetes in Goto-Kakizaki rats.

Kynurenic acid (KYNA) is an endogenous catabolite of tryptophan that has been found to demonstrate neuroprotective properties in psychiatric disorders. Recently, accumulating data have suggested that KYNA may also play a significant role in various metabolic diseases by stimulating energy metabolism in adipose tissue and muscle. However, whether KYNA can serves as an anti-diabetes agent has yet to be studied. In this study, we investigated the potential anti-diabetic effects of administering KYNA orally through drinking water in pre-diabetic Goto-Kakizaki rats and examined how this treatment may influence energy metabolism regulation within the liver. We found that hyperglycemic Goto-Kakizaki rats showed lower plasmatic KYNA levels compared to normal rats. Oral administration of KYNA significantly delayed the onset of diabetes in Goto-Kakizaki rats compared to untreated animals. Moreover, we found that KYNA treatment significantly increased respiration exchange ratio and promoted the energy expenditure by stimulating the expression of uncoupling protein (UCP). We confirmed that KYNA stimulated the UCP expression in HepG2 cells and mouse hepatocytes at mRNA and protein levels. Our study reveals that KYNA could potentially act as an anti-diabetic agent and KYNA-induced UCP upregulation is closely associated with the regulation of energy metabolism. These results provide further evidence for the therapeutic potential of KYNA in diabetes.

Transcriptomics reveals amygdala neuron regulation by fasting and ghrelin thereby promoting feeding.

The central amygdala (CeA) consists of numerous genetically defined inhibitory neurons that control defensive and appetitive behaviors including feeding. Transcriptomic signatures of cell types and their links to function remain poorly understood. Using single-nucleus RNA sequencing, we describe nine CeA cell clusters, of which four are mostly associated with appetitive and two with aversive behaviors. To analyze the activation mechanism of appetitive CeA neurons, we characterized serotonin receptor 2a (Htr2a)-expressing neurons (CeAHtr2a) that comprise three appetitive clusters and were previously shown to promote feeding. In vivo calcium imaging revealed that CeAHtr2a neurons are activated by fasting, the hormone ghrelin, and the presence of food. Moreover, these neurons are required for the orexigenic effects of ghrelin. Appetitive CeA neurons responsive to fasting and ghrelin project to the parabrachial nucleus (PBN) causing inhibition of target PBN neurons. These results illustrate how the transcriptomic diversification of CeA neurons relates to fasting and hormone-regulated feeding behavior.

Fractal Analysis on Machined Surface Morphologies of Soft-Brittle KDP Crystals Processed by Micro Ball-End Milling.

The micro-defects on KH2PO4 (KDP) optic surfaces are mainly repaired by the micro-milling technique, while it is very easy to introduce brittle cracks on repaired surfaces, as KDP is soft and brittle. To estimate machined surface morphologies, the conventional method is surface roughness, but it fails to distinguish ductile-regime machining from brittle-regime machining directly. To achieve this objective, it is of great significance to explore new evaluation methods to further characterize machined surface morphologies. In this study, the fractal dimension (FD) was introduced to characterize the surface morphologies of soft-brittle KDP crystals machined by micro bell-end milling. The 3D and 2D fractal dimensions of the machined surfaces and their typical cross-sectional contours have been calculated, respectively, based on Box-counting methods, and were further discussed comprehensively by combining the analysis of surface quality and textures. The 3D FD is identified to have a negative correlation with surface roughness (Sa and Sq), meaning the worse the surface quality the smaller the FD. The circumferential 2D FD could quantitively characterize the anisotropy of micro-milled surfaces, which could not be analyzed by surface roughness. Normally, there is obvious symmetry of 2D FD and anisotropy on the micro ball-end milled surfaces generated by ductile-regime machining. However, once the 2D FD is distributed asymmetrically and the anisotropy becomes weaker, the assessed surface contours would be occupied by brittle cracks and fractures, and corresponding machining processes will be in a brittle regime. This fractal analysis would facilitate the accurate and efficient evaluation of the repaired KDP optics by micro-milling.

Transcriptome and Pathway Analysis Reveals that Adipose-derived Stem Cells Target Inflammatory Factors and Delay the Progression of Diabetic Liver Disease.

BACKGROUND: Diabetic liver disease is one of the main complications that leads to the aggravation of diabetes, but it has not received sufficient attention. This study aimed to provide a better understanding of the altered molecular networks in in diabetic rats with liver damage after stem cell therapy. To a certain extent, our research would be instructive, since almost no studies of this kind have been performed on patients with diabetic liver disease after stem cell therapy. METHODS: Streptozotocin-induced diabetic rats were treated with adipose-derived stem cells. RNA-Seq analysis was performed on the liver tissues of these animals, and key pathway factors were further identified and validated. RESULTS: RNA-Seq analysis revealed numerous affected signaling pathways and functional categories. The results showed that the network of dual specificity phosphatase 1 (DUSP1), an oxidative stress-related gene, was prominently activated in the liver after stem cell therapy, and the enrichment of genes associated with liver damage, steatosis and fibrosis was also detected. The extracellular regulated protein kinase (ERK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway may be involved in this process by regulating the nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. CONCLUSIONS: These data provide novel insights into liver biology, suggest common alterations in the molecular networks during diabetic liver damage, and show the advantages of stem cell therapy, indicating its further application potential for early treatment of diabetic liver damage and delaying the progression of liver fibrosis in the later stage.

Effect of Pre-Existing Micro-Defects on Cutting Force and Machined Surface Quality Involved in the Ball-End Milling Repairing of Flawed KDP Crystal Surfaces.

When serving in extremely high-power laser conditions, KH2PO4 (KDP) surfaces are susceptible to incur laser damage points (also known as defects). Using micro-ball end milling cutters to repair and remove the pre-existing damage points on the flawed KDP crystal surface is the most effective method to control the growth of laser damage points on KDP crystal surfaces and prolong their service life. However, there are various forms of micro-defects (such as pits, scratches and brittle fractures) around the laser damage points on KDP crystal surfaces which possess remarkable effects on the micro-milling repair process and consequently deteriorate the repair quality. In this work, combined with nano-indentation experiments, elastic-plastic mechanics and fracture mechanics theory, a constitutive model considering the anisotropic property of KDP crystals and a three-dimensional (3D) finite element model (FEM) were established to simulate the cutting force and surface topography involved in the ball-end milling repairing of flawed KDP crystal surfaces. Besides, the micro-milling experiments were conducted to evaluate the change of cutting force and machined surface quality in the presence of micro-defects with various feed rates. The results show that micro-defects would induce the fluctuation of cutting force and a change of the undeformed cutting thickness (UCT) in the process of repairing the damage points on the crystal surface, which would lead to the brittle-ductile transition (BDT) and affect the machined surface quality. The machined surface quality was found to be deteriorated by the pre-existing micro-defects when the UCT was small (the UCT was less than 375 nm). On the contrary, brittle mode cutting in the local area can be transformed into ductile mode cutting, resulting in an improvement of repaired surface quality that is exhibited by the cutting force and microtopography. This work has great theoretical significance and engineering practical value for the promotion and application of micro-milling repairing technology in the practical manufacturing and operation of KDP optics applied to high-power laser systems.

Determination of intrinsic defects of functional KDP crystals with flawed surfaces and their effect on the optical properties.

A practically nonlinear optical material, the functional KH2PO4 (KDP) crystal, has an extremely low laser-induced damage threshold (LIDT) due to manufacturing-induced surface defects. The low LIDT induced by these surface defects of KDP crystals hinders their application in laser fusion facilities. Herein, the effect of intrinsic point defects introduced by manufacturing-induced lateral cracks on laser damage was particularly investigated by a combination of spectral detection (i.e., photoluminescence, Raman and Fourier transformed infrared spectra) and first-principles calculation. It was determined that the manufacturing-induced lateral cracks would introduce more hydrogen vacancy and oxygen vacancy intrinsic defects than the ideal surface. These intrinsic defects would form cluster-type defects, lowering the LIDT to 6.600 J cm-2 by introducing two defect levels of 2.83 eV and 4.89 eV within the band gap of the KDP crystal. To further investigate the effect of intrinsic defects introduced by lateral cracks on laser-induced damage growth, the transformation of charge states of intrinsic defects under laser irradiation was calculated. Combined with the spectral information of the lateral crack-induced laser damage site and the laser damage growth experiments, it was found that the intrinsic defects of lateral cracks have a large amount of evolution, making the crystal prone to severe damage growth. Overall, the avoidance of such lateral cracks with a large number of intrinsic defects is very beneficial for improving the laser damage resistance of KDP crystals.

Analysis on the difference of skin surface lipids during blue light therapy for acne by lipidomics.

Acne is a chronic inflammatory skin disease of the sebaceous glands of the hair follicles, caused by a variety of factors and tends to recur, causing skin damage and psychological stress to patients. Blue light (415nm) is a popular physical therapy for acne, however, studies on the effects of blue light on skin surface lipids (SSL) have not been exhaustively reported. So, we want to investigate the difference in SSL before and after acne treatment with blue light and to reveal the potential mechanism of acne treatment with blue light from the lipid level. SSL samples were collected and physiological indicators (moisture content, transepidermal water loss (TEWL), sebum content and pH) were measured. By using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) with multivariate data analysis methods to obtain specific information on the lipid composition. Analysis of the physiological index data showed a significant increase in moisture content (p = 0.042), pH (p = 0.000) and a significant decrease in sebum content(p = 0.008) in the after treatment area (AT group), while there was no significant change in TEWL values. A total of 2398 lipids were detected by lipidomics analysis and 25 differential lipids were screened. Triradylglycerols (TGs), isoprenoids and hopanoids being the potential differential lipids. Among the lipids associated with the skin barrier, only monounsaturated fatty acids (MUFA) (p = 0.045) were significantly increased. This study revealed significant changes in SSL after blue light treatment for acne, suggesting that blue light exposure may cause changes in the relative lipid content and redistribution of lipid components, and that whether it damages the skin barrier requires further study.

Adipose-derived stem cells alleviate liver injury induced by type 1 diabetes mellitus by inhibiting mitochondrial stress and attenuating inflammation.

BACKGROUND: Type 1 diabetes mellitus (T1D) is a worldwide health priority due to autoimmune destruction and is associated with an increased risk of multiorgan complications. Among these complications, effective interventions for liver injury, which can progress to liver fibrosis and hepatocellular carcinoma, are lacking. Although stem cell injection has a therapeutic effect on T1D, whether it can cure liver injury and the underlying mechanisms need further investigation. METHODS: Sprague-Dawley rats with streptozotocin (STZ)-induced T1D were treated with adipose-derived stem cell (ADSC) or PBS via the tail vein formed the ADSC group or STZ group. Body weights and blood glucose levels were examined weekly for 6 weeks. RNA-seq and PCR array were used to detect the difference in gene expression of the livers between groups. RESULTS: In this study, we found that ADSCs injection alleviated hepatic oxidative stress and injury and improved liver function in rats with T1D; potential mechanisms included cytokine activity, energy metabolism and immune regulation were potentially involved, as determined by RNA-seq. Moreover, ADSC treatment altered the fibroblast growth factor 21 (FGF21) and transforming growth factor ß (TGF-ß) levels in T1D rat livers, implying its repair capacity. Disordered intracellular energy metabolism, which is closely related to mitochondrial stress and dysfunction, was inhibited by ADSC treatment. PCR array and ingenuity pathway analyses suggested that the ADSC-induced suppression of mitochondrial stress is related to decreased necroptosis and apoptosis. Moreover, mitochondria-related alterations caused liver inflammation, resulting in liver injury involving the T lymphocyte-mediated immune response. CONCLUSIONS: Overall, these results improve our understanding of the curative effect of ADSCs on T1D complications: ADSCs attenuate liver injury by inhibiting mitochondrial stress (apoptosis and dysfunctional energy metabolism) and alleviating inflammation (inflammasome expression and immune disorder). These results are important for early intervention in liver injury and for delaying the development of liver lesions in patients with T1D.

The relationship between adolescent risk perception and emotions during the COVID-19: a short-term longitudinal study.

This study explores the relationship between adolescents' perceptions of epidemic risk and their emotions through three follow-up surveys during the early stages of the COVID-19 pandemic on February 11th (T1), 18th (T2), and 25th (T3), 2020. Three hundred and four adolescents in different academic stages (junior high middle school, senior high middle school, and university) participated in the online survey, and cross-lag analysis was used to examine the causal relationship between epidemic risk perceptions and positive and negative emotions. The results found that the individual's positive emotions were significantly higher than the negative emotions in T1, T2 and T3. Cross-lag analysis found that for positive emotions, T2 positive emotions could negatively predict T3 epidemic risk perceptions, and T2 epidemic risk perceptions could negatively predict the individual's T3 positive emotions. For negative emotions, risk perceptions at T1 could positively predict negative emotions at T2, and at the same time, negative emotions at T1 could also positively predict epidemic risk perceptions at T2. This indicates that during the early stages of the COVID-19 pandemic, there was a causal relationship between the perceptions of epidemic risk and the emotions of adolescents, and this relationship had high stability among groups of different genders and academic stages.

Long non-coding RNA HOXA11 antisense RNA upregulates spermatogenesis-associated serine-rich 2-like to enhance cisplatin resistance in laryngeal squamous cell carcinoma by suppressing microRNA-518a.

Long noncoding RNAs (LncRNAs) are closely associated with the chemoresistance of laryngeal squamous cell carcinoma (LSCC). Previous studies indicated that HOXA11-AS could function as a vital regulator in human cancers. However, the regulatory mechanisms of HOXA11-AS in the chemoresistance of LSCC remain unclear. In this study, it was found that HOXA11-AS expression was upregulated in cisplatin (CDDP)-resistant LSCC tissues and cells. Loss-of-function assays revealed that HOXA11-AS knockdown inhibited the viability, migration, and invasion, but promoted the apoptosis of CDDP-resistant LSCC cells. Meanwhile, we identified miR-518a as a downstream gene of HOXA11-AS in LSCC, and miR-518a silencing reversed the promotive effect of HOXA11-AS knockdown on CDDP sensitivity of LSCC cells. In addition, miR-518a could inhibit spermatogenesis-associated serine-rich 2-like (SPATS2L) expression by direct interaction, and upregulation of SPATS2L abrogated the inhibitory effect of HOXA11-AS silencing or miR-518a overexpression on CDDP resistance of CDDP-resistant LSCC cells. In sum, our results demonstrated that HOXA11-AS enhanced CDDP resistance of LSCC via miR-518a/SPATS2L axis, which might offer novel therapeutic strategies for CDDP-resistant LSCC.

Study of the protective effects of cosmetic ingredients on the skin barrier, based on the expression of barrier-related genes and cytokines.

BACKGROUND: Sensitive skin is the result of a complex process that is closely linked to the damage of the skin barrier. There are no recognized methods for evaluating the efficacy of anti-allergy products. METHODS: In this study, a model of skin barrier damage was created by treating HaCaT cells with 60 µg/ml of sodium dodecyl sulfate for 48 h. The protective effects of nine cosmetic ingredients, including oat extract (S1), on the skin barrier were investigated based on the gene expression levels of aquaporin3 (AQP3), filaggrin (FLG), caspase-14 (CASP14), and human tissue kallikrein7 (KLK7), as well as those of various interleukins (IL) and vascular endothelial growth factor (VEGF). RESULTS: Among the nine ingredients, S1 had a good protective effect on the function of the skin barrier. It promoted the expression of AQP3, FLG, and CASP14, while inhibiting the expression of KLK7 in HaCaT cells, at a concentration of 0.06%. It also maintained IL-6, IL-8, and VEGF at appropriate levels while promoting the proliferation and differentiation of HaCaT cells. CONCLUSIONS: The above indicators allow for the preliminary establishment of a method to evaluate the efficacy of the barrier protection ability of sensitive skin.

Effects of Probiotic Supplementation on Inflammatory Markers and Glucose Homeostasis in Adults With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Background: Several studies have revealed the effect of probiotic supplementation in patients with type 2 diabetes (T2DM) on the amelioration of low-grade inflammation, which plays an important role in the pathogenesis of T2DM. However, the effects of the clinical application of probiotics on inflammation in individuals with T2DM remain inconsistent. This study aims to investigate the comprehensive effects of probiotics on inflammatory markers in adults with T2DM. Methods: PubMed, Embase, Cochrane Library, and the Web of Science were searched to identify randomized controlled trials (RCTs) exploring the effect of probiotic supplementation on inflammatory markers in individuals with T2DM through March 11, 2021. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. We used a random-effects model to calculate the standardized mean difference (SMD) between the probiotic supplementation and control groups. Results: Seventeen eligible studies were selected with a total of 836 participants, including 423 participants in probiotic supplementation groups and 413 participants in control groups. Our study demonstrated that compared with the control condition, probiotic intake produced a beneficial effect in reducing the levels of plasma inflammation markers, including tumour necrosis factor-α (TNF-α) (SMD [95% CI]; -0.37 [-0.56, -0.19], p < 0.0001) and C-reactive protein (CRP) (SMD [95% CI]; -0.21 [-0.42, -0.01], p = 0.040), while it had no effect on the plasma interleukin-6 (IL-6) level (SMD [95% CI]; -0.07 [-0.27, 0.13], p = 0.520). In addition, our results support the notion that probiotic supplementation improves glycaemic control, as evidenced by a significant reduction in fasting blood glucose (FPG), HbA1c and HOMA-IR (SMD [95% CI]: -0.24 [-0.42, -0.05], p = 0.010; -0.19 [-0.37, -0.00], p = 0.040; -0.36 [-0.62, -0.10], p = 0.006, respectively). Conclusion: Our study revealed some beneficial effects of probiotic supplementation on improving inflammatory markers and glucose homeostasis in individuals with T2DM. Probiotics might be a potential adjuvant therapeutic approach for T2DM.