Germacrone, isolated from Curcuma wenyujin, inhibits melanin synthesis through the regulation of the MAPK signaling pathway.

Abnormal melanin synthesis causes hyperpigmentation disorders, such as chloasma, freckles, and melanoma, which are highly multiple and prevalent. There were few reports on the anti-melanogenic effect of Curcuma wenyujin Y.H. Chen et C. Ling, and the bioactive compound has not been elucidated as well. The study aims to investigate the anti-melanogenic effect of C. wenyujin, and identify the bioactive compound, and further explore its underlying mechanism. Our results showed that the Petroleum ether fraction extracted from C. wenyujin rhizome had a significant anti-melanogenic effect, and germacrone isolated from it was confirmed as the major bioactive compound. To our data, germacrone significantly inhibited tyrosinase (TYR) activity, reduced melanosome synthesis, reduced dendrites formation of B16F10 cells, and melanosome transport to keratinocytes. Moreover, germacrone effectively decreased the hyperpigmentation in zebrafish and the skin of guinea pigs in vivo. Western-blot analysis showed that germacrone down-regulated the expression of TYR, TRP-1, TRP-2, Rab27a, Cdc42, and MITF proteins via the activation of the MAPK signaling pathway. Taken together, germacrone is an effective bioactive compound for melanogenesis inhibition. Our studies suggest that germacrone may be considered a potential candidate for skin whitening.

Curcuma wenyujin rhizomes extract ameliorates lipid accumulation.

Curcuma wenyujin (C. wenyujin) is a medicinal plant that is traditionally used to treat blood stagnation, liver fibrosis, pain, and jaundice. In this study, we examined the effect of C. wenyujin rhizome extract on hepatic lipid accumulation both in vivo and in vitro. We found that the petroleum ether fraction of C. wenyujin rhizome extract (CWP) considerably reduced the accumulation of lipids in HepG2 cells treated with oleic and palmitic acid. Ultra-high-performance liquid chromatography coupled with LTQ-Orbitrap mass spectrometry was used to analyze the main chemical constituents of CWP, and 21 sesquiterpenes were identified. In vivo experiments revealed that the administration of CWP significantly reduced the body weight and serum total cholesterol (TC) level of low-density-lipoprotein receptor knockout mice treated with a high-fat diet without affecting their food intake. CWP also significantly reduced the levels of liver TC, liver triglycerides, aspartate transaminase, and alanine transaminase. Histological examination revealed that CWP dose-dependently reduced steatosis in liver tissue, significantly downregulated the expression of lipogenesis genes, and increased the ß-oxidation of fatty acids. CWP also significantly increased autophagy-related proteins. In conclusion, CWP rich in sesquiterpenes reduces the accumulation of lipids in vivo and in vitro by improving lipid metabolism and activating autophagy.

[Study on allergen components of birch pollen in Beijing area].

Objective:To explore the allergen components of birch pollen in the Beijing area and interpret its clinical significance. Methods:A total of 58 patients with birch pollen allergy were included in the cross-sectional study and divided into allergic rhinitis（AR） and allergic asthma（AA） groups according to clinical manifestations. Concentration of birch pollen allergen sIgE, as well as Bet v 1, Bet v 2, Bet v 4 and Bet v 6 sIgE were detected by ImmunoCAP immunolinked immunoassay. Differences of sIgE concentration of birch pollen allergen component in AR and AA were analyzed. Results:There were 44（75.9%） cases of AR and 14（24.1%） cases of AA were enrolled. All the 18 patients with spring pollen allergy were AR patients without AA. There were 40 cases with both spring and autumn pollen allergy, of which 26 cases（65%） were AR and 14 cases（35%） were AA. The sIgE of birch pollen allergen was level 2 or above in all subjects. 94.8% were positive for any four allergen components. 77.6% were mono-sensitized to any allergen component while 17.2% were dual-sensitized. The positive rate of Bet v 1 and/or Bet v 2 was 93.1%. The positive rates of four protein components were: Bet v 1（82.8%）, Bet v 2（29.3%）, Bet v 6（1.7%）, Bet v 4（0%）. sIgE of birch pollen was positively correlated with sIgE level of Betv 1（r=0.898, P<0.001）. The sIgE concentration of Bet v2 in AA group was significantly higher than that in AR group（[4.34±14.35] kUA/L vs [1.56±3.26] kUA/L, P<0.05）. There was no significant difference in other components. Conclusion:Bet v 1 is the main allergen component of birch pollen in the Beijing area, and Bet v 1 plus Bet v 2 can diagnose more than 90% of birch pollen allergy.

Effects of polyphenol and gelatin types on the physicochemical properties and emulsion stabilization of polyphenol-crosslinked gelatin conjugates.

Herein, six types of polyphenol-crosslinked gelatin conjugates (PGCs) with ≥ two gelatin molecules were prepared using a covalent crosslinking method with two types of polyphenols (tannic acid and caffeic acid) and three types of gelatins (bovine bone gelatin, cold water fish skin gelatin, and porcine skin gelatin) for the emulsion stabilization. The structural and functional properties of the PGCs were dependent on both polyphenol and gelatin types. The storage stability of the conjugate-stabilized emulsions was dependent on the polyphenol crosslinking, NaCl addition, and heating pretreatment. In particular, NaCl addition promoted the liquid-gel transition of the emulsions: 0.2 mol/L > 0.1 mol/L > 0.0 mol/L. Moreover, NaCl addition also increased the creaming stability of the emulsions stabilized by PGCs except tannic acid-crosslinked bovine bone gelatin conjugate. All the results provided useful knowledge on the effects of molecular modification and physical processing on the properties of gelatins.

Tetrazole and acylsulfonamide bioisosteric replacements of the carboxylic acid in a dual MCL-1/BCL-xL inhibitor are tolerated.

Overexpression of the anti-apoptotic protein MCL-1 is associated with a plethora of human cancers, and it reduces the sensitivity of cancer cells to approved chemotherapies. Accordingly, the discovery of MCL-1 inhibitors is an active area of interest. Many inhibitors of the anti-apoptotic MCL-1 protein bear a crucial carboxylic acid that may engage Arg263 in the BH3-binding groove. We previously described the salicylic acid-based dual MCL-1/BCL-xL inhibitor 17cd, which is currently undergoing lead optimization. As part of that process, we wished to investigate bioisosteric replacement of 17cd's key carboxylic acid. Herein we describe the synthesis of a variety of analogues of a simpler analogue of 17cd presenting carboxylic acid surrogates. The acylsulfonamide and tetrazole motifs, which exhibit comparable pKas to the carboxylic acid function, displayed similar, or better, binding affinities to MCL-1 and BCL-xL as the corresponding carboxylic acid-containing lead. Our best compound was acylsulfonamide 7d with a Ki of 800 nM against MCL-1 and 1.82 mM against BCL-xL, and demonstrated an improved effect on the viability of the HL60 acute myeloid leukemia cell line relative to the parent carboxylic acid-containing dual inhibitor from which it was derived.

p53 deacetylation alleviates calcium oxalate deposition-induced renal fibrosis by inhibiting ferroptosis.

Calcium oxalate (CaOx) stones are among the most common types of kidney stones and are associated with renal tubular damage, interstitial fibrosis, and chronic kidney disease. The mechanism of CaOx crystal-induced renal fibrosis remains unknown. Ferroptosis, a type of regulated cell death, is characterised by iron-dependent lipid peroxidation, and the tumour suppressor p53 is a key regulator of ferroptosis. In the present study, our results demonstrated that ferroptosis was significantly activated in patients with nephrolithiasis and hyperoxaluric mice as well as verified the protective effects of ferroptosis inhibition on CaOx crystal-induced renal fibrosis. Moreover, the single-cell sequencing database, RNA-sequencing, and western blot analysis revealed that the expression of p53 was increased in patients with chronic kidney disease and the oxalate-stimulated human renal tubular epithelial cell line, HK-2. Additionally, the acetylation of p53 was enhanced by oxalate stimulation in HK-2 cells. Mechanistically, we found that the induction of p53 deacetylation, owing to either the SRT1720-induced activation of deacetylase sirtuin 1 or the triple mutation of p53, inhibited ferroptosis and alleviated renal fibrosis caused by CaOx crystals. We conclude that ferroptosis is one of the critical mechanisms contributing to CaOx crystal-induced renal fibrosis, and the pharmacological induction of ferroptosis via sirtuin 1-mediated p53 deacetylation may be a potential target for preventing renal fibrosis in patients with nephrolithiasis.

Can Axillary Lymph Node Dissection be Omitted in Breast Cancer Patients with Metastatic Sentinel Lymph Nodes Undergoing Mastectomy? A Systematic Review and Meta-Analysis of Real-World Evidence.

BACKGROUND: The omission of axillary lymph node dissection (ALND) in patients with breast cancer who have metastatic sentinel lymph nodes (SLNs) undergoing mastectomy remains controversial. This meta-analysis explored the clinicopathological factors affecting the selection of ALND and the influences of ALND on survival outcomes in patients receiving mastectomy with positive SLNs. METHODS: Eligible studies published prior to 31 December 2022 were selected by searching the Embase, Web of Science and PubMed databases. Pooled analyses were performed using the number of events for clinicopathological parameters and HRs with 95% CIs for survival outcomes including disease-free survival (DFS), overall survival (OS), distant recurrence-free survival (DRFS) and locoregional recurrence-free survival (LRFS). RESULTS: A total of 10 retrospective studies enrolling only breast cancer patients with limited SLN metastases (no more than 3 positive SLNs or micrometastatic SLNs) undergoing mastectomy were included. Performing ALND in mastectomy patients who had limited SLN metastases was significantly correlated with invasive ductal carcinomas, larger tumors, lymphovascular invasion, higher tumor grade, macrometastatic SLNs, more positive SLNs, extranodal extension, positive surgical margins, negative ER, administration of adjuvant chemotherapy and nonwhite race (P < 0.05). However, performing ALND did not result in significantly longer OS, DFS, LRFS or DRFS (P > 0.05) in these patients. CONCLUSION: The present meta-analysis indicated that ALND may be safely avoided in patients with breast cancer who had limited SLN metastases undergoing mastectomy. Further well-designed randomized clinical trials are warranted to validate our results.

Structures, Sources, Identification/Quantification Methods, Health Benefits, Bioaccessibility, and Products of Isorhamnetin Glycosides as Phytonutrients.

In recent years, people have tended to consume phytonutrients and nutrients in their daily diets. Isorhamnetin glycosides (IGs) are an essential class of flavonoids derived from dietary and medicinal plants such as Opuntia ficus-indica, Hippophae rhamnoides, and Ginkgo biloba. This review summarizes the structures, sources, quantitative and qualitative analysis technologies, health benefits, bioaccessibility, and marketed products of IGs. Routine and innovative assay methods, such as IR, TLC, NMR, UV, MS, HPLC, UPLC, and HSCCC, have been widely used for the characterization and quantification of IGs. All of the therapeutic effects of IGs discovered to date are collected and discussed in this study, with an emphasis on the relevant mechanisms of their health-promoting effects. IGs exhibit diverse biological activities against cancer, diabetes, hepatic diseases, obesity, and thrombosis. They exert therapeutic effects through multiple networks of underlying molecular signaling pathways. Owing to these benefits, IGs could be utilized to make foods and functional foods. IGs exhibit higher bioaccessibility and plasma concentrations and longer average residence time in blood than aglycones. Overall, IGs as phytonutrients are very promising and have excellent application potential.

Exome Sequencing Reveals SLC4A11 Variant Underlying Congenital Hereditary Endothelial Dystrophy (CHED2) Misdiagnosed as Congenital Glaucoma.

Autosomal recessive congenital hereditary endothelial dystrophy (CHED2) may be misdiagnosed as primary congenital glaucoma (PCG) due to similar clinical phenotypes during early infancy. In this study, we identified a family with CHED2, which was previously misdiagnosed as having PCG, and followed up for 9 years. Linkage analysis was first completed in eight PCG-affected families, followed by whole-exome sequencing (WES) in family PKGM3. The following in silico tools were used to predict the pathogenic effects of identified variants: I-Mutant 2.0, SIFT, Polyphen-2, PROVEAN, mutation taster and PhD-SNP. After detecting an SLC4A11 variant in one family, detailed ophthalmic examinations were performed again to confirm the diagnosis. Six out of eight families had CYP1B1 gene variants responsible for PCG. However, in family PKGM3, no variants in the known PCG genes were identified. WES identified a homozygous missense variant c.2024A>C, p.(Glu675Ala) in SLC4A11. Based on the WES findings, the affected individuals underwent detailed ophthalmic examinations and were re-diagnosed with CHED2 leading to secondary glaucoma. Our results expand the genetic spectrum of CHED2. This is the first report from Pakistan of a Glu675Ala variant with CHED2 leading to secondary glaucoma. The p.Glu675Ala variant is likely a founder mutation in the Pakistani population. Our findings suggest that genome-wide neonatal screening is worthwhile to avoid the misdiagnosis of phenotypically similar diseases such as CHED2 and PCG.

COMPARING FUNCTIONAL AND VASCULAR LAYER OUTCOMES OF LASER PHOTOCOAGULATION VERSUS SUBTHRESHOLD MICROPULSE LASER FOR DIABETIC MACULAR EDEMA: An OCT-Angiography Study.

PURPOSE: To compare the efficacy of conventional laser and subthreshold micropulse laser (SML) in treating diabetic macular edema in terms of functional outcomes and changes in quantitative metrics for the retinal capillary and choriocapillary vascular layers. METHODS: Fifty-two eyes from 52 patients with treatment-naive, clinically significant macular edema were randomly assigned to the conventional laser group or SML group in a 1:1 ratio. Best-corrected visual acuity, central macular thickness (CMT), and optical coherence tomography angiography scans were measured at baseline, 1, 3, and 6 months after treatment. RESULTS: The SML group showed rapid visual recovery, improving from baseline of 0.320 ± 0.31 logarithm of the minimum angle of resolution (20/42 Snellen) to 0.270 ± 0.22 logarithm of the minimum angle of resolution (20/37 Snellen) at 1 month ( P = 0.038) and had significant improvements in CMT at 6-month post-treatment (353.88-301.00 µ m, P = 0.005). Statistically significant changes were detected across all optical coherence tomography angiography metrics, including vessel density, vessel length density, vessel diameter index, and fractal dimension, at 6 months for both groups in the deep capillary plexus and choriocapillary plexus. CONCLUSION: Subthreshold micropulse laser resulted in early visual recovery and sustained macular thickness improvement in the treatment of diabetic macular edema. Microvascular perfusion parameters, including vessel density, vessel length density, and fractal dimension, improved in the deep capillary plexus and choriocapillary plexus for both treatment groups at 6 months post-treatment.

Discovery of N-sulfonylated aminosalicylic acids as dual MCL-1/BCL-xL inhibitors.

The anti-apoptotic protein MCL-1, which is overexpressed in multiple cancers, is presently a focus for the development of targeted drugs in oncology. We previously discovered inhibitors of MCL-1 based on 1-sulfonylated 1,2,3,4-tetrahydroquinoline-6-carboxylic acids ("1,6-THQs"). However, with the nitrogen atom constrained in the bicyclic ring, we were unable to modify the alkyl portion of the tertiary sulfonamide functionality. Moreover, the introduction of additional functional groups onto the benzene ring portion of the THQ bicycle would not be trivial. Therefore, we elected to deconstruct the piperidine-type ring of the 6-carboxy-THQ lead to create a new 4-aminobenzoic acid scaffold. Given its simplicity, this permitted us to introduce diversity at the sulfonamide nitrogen, as well as vary the positions and substituents of the benzene ring. One of our most potent MCL-1 inhibitors, 6e-OH, exhibited a K i of 0.778 µM. Heteronuclear single quantum coherence experiments suggested 6e-OH bound in the canonical BH3-binding groove, with significant perturbations of R263, which forms a salt bridge with MCL-1's pro-apoptotic binding partners, as well as residues in the p2 pocket. Selectivity studies indicated that our compounds are dual inhibitors of MCL-1 and BCL-xL, with 17cd the most potent dual inhibitor: K i = 0.629 µM (MCL-1), 1.67 µM (BCL-xL). Whilst selective inhibitors may be more desirable in certain instances, polypharmacological agents whose additional target(s) address other pathways associated with the disease state, or serve to counter resistance mechanisms to the primary target, may prove particularly effective therapeutics. Since selective MCL-1 inhibition may be thwarted by overexpression of sister anti-apoptotic proteins, including BCL-xL and BCL-2, we believe our work lays a solid foundation towards the development of multi-targeting anti-cancer drugs.

Effect of transmembrane protein 100 on prostate cancer progression by regulating SCNN1D through the FAK/PI3K/AKT pathway.

The effects of transmembrane (TMEM) proteins in the progression of prostate cancer (PCa) remain unknown. This study aims to explore the functions of TMEM100 in PCa. To explore the expression, regulation, and effects of TMEM100 in PCa, two PCa cell lines and 30 PCa tissue samples with adjacent control tissues were examined. Online databases, immunohistochemistry, immunofluorescence, western blot, flow cytometry, colony formation, wound healing, transwell assays, and xenograft mouse models were used to explore effects of TMEM100 relevant to PCa. TMEM100 expression was shown to decrease in PCa patients, and low TMEM100 expression was associated with tumor stage and metastasis. Overexpression of TMEM100 suppressed PCa progression by inhibiting the FAK/PI3K/AKT signaling pathway. Tumor size was smaller in TMEM100 overexpressing PCa cells in xenograft mice than in control mice. We also found that TMEM100 could regulate SCNN1D by inhibiting FAK/PI3K/AKT signaling in PCa cell lines. Taken together, our findings indicate that TMEM100 is a tumor suppressor that plays a vital role in preventing PCa proliferation, migration, and invasion through inhibition of FAK/PI3K/AKT signaling. These studies suggest that TMEM100 can be used as a predictive biomarker and therapeutic target.

Effects of Five-Step Nutritional Interventions Conducted by a Multidisciplinary Care Team on Gastroenteric Cancer Patients Undergoing Chemotherapy: A Randomized Clinical Trial.

The present study aims to report a five-step nutritional intervention conducted by a multidisciplinary care team as well as to investigate its effects on the nutritional status and quality of life of gastroenteric cancer patients undergoing chemotherapy. A total of 176 patients with newly diagnosed gastroenteric cancer were enrolled in the observational study. The nutritional status of the patients was assessed using Patient-Generated Subjective Global Assessment (PG-SGA) and Nutritional Risk Screening-2002 (NRS-2002), and anthropometry and biological tests were performed. Patients were randomly divided into intervention group (n = 40) and control group (n = 38). Patients in the intervention group received five-step nutrition intervention, while the control group received routine nutrition management. In the newly diagnosed patients with gastroenteric cancer, 50% presented mild to moderate malnutrition, 29.5% presented severe malnutrition, while only 20.5% of patients were in good nutritional status. Nutritional interventions reduced the progression of malnutrition after 10 weeks. Anthropometric parameters increased as well as function and symptoms improved; therefore, controlled the decline in quality of life. To sum up, five-step nutritional interventions conducted by a multidisciplinary care team improved the nutritional status of patients with gastroenteric cancer undergoing chemotherapy, and showed positive impacts on quality of life.

Low-density lipoprotein receptor deficiency reduced bone mass in mice via the c-fos/NFATc1 pathway.

AIM: The low-density lipoprotein receptor (LDLR) plays a crucial role in regulating lipid metabolism. However, whether LDLR deficiency affects bone mass and morphology remains controversial. This study aimed to analyze the bone phenotypes of LDLR knockout (LDLR-/-) mice. MAIN METHODS: Eight-week-old LDLR-/- and wild-type (WT) mice were subjected to microcomputed tomography to detect bone phenotypes. Enzyme-linked immunosorbent assay kits were used to detect the serum estrogen levels and matrix metalloproteinase 9 (MMP-9) levels in tissue homogenates. Von Kossa, toluidine blue, tartrate-resistant acid phosphatase (TRAP) staining, and calcein labeling were performed to explore bone turnover parameters. In vitro, osteoclastogenesis was induced in bone marrow cells from LDLR-/- mice and WT mice in the presence or absence of 17ß-estradiol. The microphotographs and number of osteoclasts were validated using TRAP staining. Relative gene expression during osteoclast differentiation and maturation was determined by quantitative real-time polymerase chain reaction. KEY FINDINGS: LDLR deficiency results in reduced bone mineral density of the tibial cancellous bone, indicating bone loss to some extent in LDLR-/- mice. LDLR deficiency significantly increased the number of osteoclasts, but not osteoblasts. In vitro, bone marrow cells from LDLR-/- mice displayed enhanced osteoclastic potential along with increased expression of TRAP, cathepsin K, nuclear factor of activated T-cells 1 (NFATc1), c-fos, and MMP-9 and inhibited dendritic cell-specific transmembrane protein expression. Moreover, 17ß-estradiol treatment can inhibit osteoclastogenesis in vitro. SIGNIFICANCE: Our data demonstrated that LDLR deficiency promoted osteoclastogenesis by upregulating c-fos and NFATc1 expression, reducing cancellous bone mass in LDLR-/- mice.

1-Sulfonylated 1,2,3,4-tetrahydroquinoline-6-carboxylic acids as simple, readily-accessible MCL-1 inhibitors.

MCL-1 is a member of the BCL-2 family of proteins that regulates the mitochondrial pathway of apoptosis. Overexpression of MCL-1 is associated with the development and progression of a range of human cancers, and is also responsible for the onset of resistance to conventional chemotherapies. Although several MCL-1 inhibitors have now advanced to clinical trials, recent suspensions and terminations reveal the urgency with which new inhibitor chemotypes must be discovered. Building on our previous studies of a chiral, isomeric lead, we report the discovery of a new chemotype to inhibit MCL-1: 1-sulfonylated 1,2,3,4-tetrahydroquinoline-6-carboxylic acid. The nature of the sulfonyl moiety contributed significantly to the resulting inhibitory ability. For example, transforming a phenylsulfonyl group into a 4-chloro-3,5-dimethylphenoxy)phenyl)sulfonyl moiety elicited more than a 73-fold enhancement in inhibiton of MCL-1, possibly through targeting the p2 pocket in the BH3-binding groove, and so it is anticipated that further structure-activity studies here will lead to continued improvements in binding. It should be underscored that this class of MCL-1 inhibitors is readily accessible in four simple steps, is achiral and offers many avenues for optimization, all factors that are welcomed in the search for safe and effective inhibitors of this driver of cancer cell survival.

GW842166X Alleviates Osteoarthritis by Repressing LPS-mediated Chondrocyte Catabolism in Mice.

OBJECTIVE: To explore the role and underlying mechanism of GW842166X on osteoarthritis and osteoarthritis-associated abnormal catabolism. METHODS: The extracted mouse chondrocytes were treated with GW842166X followed by lipopolysaccharide (LPS). The chondrocytes were divided into the control group, LPS group, LPS+50 nmol/L GW842166X group, and LPS+100 nmol/L GW842166X group. The cytotoxicity of GW842166X was tested using the CCK-8 assay. Western blot, RT-qPCR, and ELISA were applied to evaluate the expression of the inflammatory biomarkers in mouse chondrocytes. The expression of extracellular matrix molecules was detected by the Western blot, RT-qPCR, and immunofluorescence. Additionally, the activity of NF-κB was checked by the Western blot and immunofluorescence. The mouse Hulth models were generated to examine the in vivo effects of GW842166X on osteoarthritis. Hematoxylin and eosin staining, safranin O/fast green staining, and immunohistochemistry were applied to detect the histological changes. RESULTS: GW842166X below 200 µmol/L had no cytotoxicity on the mouse chondrocytes. LPS-induced high expression of TGF-ß1, IL-10, TNF-α, and IL-6 was significantly reduced by GW842166X. In addition, GW842166X upregulated the expression of aggrecan and collagen type III, which was downregulated after the LPS stimulation. The upregulated expression of ADAMTS-5 and MMP-13 by LPS stimulation was dropped in response to the GW842166X treatment. Furthermore, LPS decreased the IκBα expression in the cytoplasm and increased the nuclear p65 expression. However, these changes were reversed by the GW842166X pretreatment. Moreover, the damages in the knees caused by the Hulth surgery in mice were restored by GW842166X. CONCLUSION: GW842166X impeded the LPS-mediated catabolism in mouse chondrocytes, thereby inhibiting the progression of osteoarthritis.

[Profiles of IgE sensitization to dust mite allergen components in patients with allergic rhinitis and asthma].

Objective:To study the differences and clinical significance of dust mite allergen components in allergic rhinitis（AR） and allergic rhinitis with asthma syndrome（ARAS） patients. Methods:The clinical data of 42 AR patients were retrospectively analyzed and patients were divided into AR and ARAS group. The serum sIgE concentrations of house dust mites were detected by ImmunoCAP system. The allergen components of Der p（Der p 1, Der p 2, Der p 7, Der p 10, Der p 21, Der p 23） and Der f（Der f 1, Der f 2） were analyzed by protein microarray method. The concentration differences of dust mite allergen and its components in AR and ARAS groups were analyzed. Results:Thirty-one cases of AR and 11 cases of ARAS were included. The positive rate of Der p and Der f was 100.0% and 97.6%, respectively. The highest sensitization rates of Der p allergen components were as following: Der p 1（73.8%）, Der f 1（66.7%）, Der f 2（64.3%） and Der p 2（61.9%）. The sensitization rates of Der f 1（100.0% vs 54.8%, P=0.006）, Der p 2（90.9% vs 51.6%, P=0.021） and Der f 2（100.0% vs 51.6%, P=0.004） in ARAS group were significantly higher than those in AR group. The sIgE concentrations of Der p in AR group were significantly lower than those in ARAS group（[7.65±12.15]kUA/L vs[15.20±18.77]kUA/L, P<0.05）. The sIgE concentrations of Der p 1（[5.39±4.61]kUA/L vs[2.03±2.97]kUA/L, P=0.013）, Der p 2（[8.82± 13.58]kUA/L vs[2.78±5.80]kUA/L, P=0.001）, Der p 23（[1.76± 3.88]kUA/L vs[0.28±0.65]kUA/L, P<0.001） was significantly higher in ARAS group than that of AR group. Correlation analysis showed that Der p 1, Der p 2, Der f 1 and Der f 2 had high positive correlation（P<0.01）. The dust mite components sensitization showed a multiple-sensitized mode. 66.7% of the 42 patients were positive for two or more components while it was 58.1% of the AR group and 90.9% of the ARAS group. The sensitization rate of 3 or more components in ARAS group was significantly higher than that in AR group（54.6% vs 29.1%, P<0.05）. Conclusion:The concentration of dust mites allergens in ARAS group is higher than that in AR group. Der p 1, Der f 1, Der p 2 and Der f 2 are the main allergen components with a higher sensitization rate in ARAS group. The concentrations of Der p 1, Der p 2 and Der p 23 were higher in ARAS group. The ARAS group is prone to multi-sensitzed to allergen components.

Vitamin D and Ocular Diseases: A Systematic Review.

The contributory roles of vitamin D in ocular and visual health have long been discussed, with numerous studies pointing to the adverse effects of vitamin D deficiency. In this paper, we provide a systematic review of recent findings on the association between vitamin D and different ocular diseases, including myopia, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), dry eye syndrome (DES), thyroid eye disease (TED), uveitis, retinoblastoma (RB), cataract, and others, from epidemiological, clinical and basic studies, and briefly discuss vitamin D metabolism in the eye. We searched two research databases for articles examining the association between vitamin D deficiency and different ocular diseases. One hundred and sixty-two studies were found. There is evidence on the association between vitamin D and myopia, AMD, DR, and DES. Overall, 17 out of 27 studies reported an association between vitamin D and AMD, while 48 out of 54 studies reported that vitamin D was associated with DR, and 25 out of 27 studies reported an association between vitamin D and DES. However, the available evidence for the association with other ocular diseases, such as glaucoma, TED, and RB, remains limited.

Icariin inhibits epithelial mesenchymal transition of renal tubular epithelial cells via regulating the miR-122-5p/FOXP2 axis in diabetic nephropathy rats.

Epithelial mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs) dominates the pathology of diabetic nephropathy (DN). microRNAs (miRNAs) can influence the fate of DN via regulation of EMT. This study aimed to analyze the role of Icariin (ICA) in EMT of RTECs, hoping to provide theoretical basis for DN management. The DN rat model was established using streptozocin, followed by ICA treatment, histopathological observation, and detection of creatinine and blood urea nitrogen. In vitro cell models were established using high glucose (HG), followed by assessment of cell proliferation, apoptosis, and migration, and E-cadherin, α-SMA, miR-122-5p, and FOXP2 expressions. Cells were transfected with miR-122-5p mimics or si-FOXP2 for joint experiments with ICA. The targeting relationship between miR-122-5p and FOXP2 was verified. ICA repaired renal dysfunctions and glomerular structure abnormities of DN rats in a dose-dependent manner. In vitro, ICA improved proliferation while suppressed migration, apoptosis, and EMT of RTECs. miR-122-5p was up-regulated in DN rats and suppressed by ICA, and miR-122-5p targeted FOXP2. miR-122-5p up-regulation or FOXP2 down-regulation reversed the protective effects of ICA on HG-induced RTECs. Overall, our finding ascertained that ICA inhibited miR-122-5p to promote FOXP2 transcription, thereby attenuating EMT of RTECs and renal injury in DN rats.

Association of Metabolic Syndrome With Prevalence of Obstructive Sleep Apnea and Remission After Sleeve Gastrectomy.

Obesity is an important risk factor for metabolic syndrome and obstructive sleep apnea (OSA). Bariatric surgery has been shown to effectively reduce weight and obesity-related comorbidities. However, the prevalence and severity of OSA in obese patients with different baseline metabolic states and the improvements of OSA after bariatric surgery remain unknown. The main aims of this study were to ascertain the prevalence of OSA in young Chinese obese patients with different metabolic states and to evaluate their respective OSA remission after laparoscopic sleeve gastrectomy. We first performed a cross-sectional study involving 123 metabolically healthy obese patients and 200 metabolically unhealthy obese patients (who had the same age and BMI ranges) to estimate the prevalence of OSA at baseline. Then we performed a retrospective study, which was registered at ClinicalTrials.gov (ref. NCT02653430) of 67 patients who underwent laparoscopic sleeve gastrectomy to evaluate the remission of OSA. Metabolically healthy and unhealthy obese patients had similar apnea-hypopnea index levels (16.6 ± 22.0 vs. 16.7 ± 18.7 events/h, P = 0.512) and prevalence of OSA (66.7% vs. 69.0%, P = 0.662). Male sex, age, waist circumference and lower liver-to-spleen ratio were independent risk factors for OSA. After laparoscopic sleeve gastrectomy, no difference was found in the decrease in body mass index (BMI) change (10.8 ± 4.8 vs. 10.8 ± 3.0 kg/m2, P = 0.996) or the decrease in the apnea-hypopnea index (18.9 ± 24.6 vs. 17.0 ± 24.0 events/h, P = 0.800). The remission of moderate-to-severe OSA was observed in the MHO (36.3%; 54.5-18.2%, P = 0.125) and MUO (32.2%; 66.1-33.9%, P = 0.001) patients. These results suggest that, in patients with obesity, metabolic syndrome does not add extra risk for the prevalence or severity of OSA. Both metabolically healthy and unhealthy obese patients could benefit equally from laparoscopic sleeve gastrectomy in terms of weight loss and obstructive sleep apnea remission.