Exploring the Traditional Chinese Medicine (TCM) database chemical space to target I7L protease from monkeypox virus using molecular screening and simulation approaches.

In the current study, we used molecular screening and simulation approaches to target I7L protease from monkeypox virus (mpox) from the Traditional Chinese Medicines (TCM) database. Using molecular screening, only four hits TCM27763, TCM33057, TCM34450 and TCM31564 demonstrated better pharmacological potential than TTP6171 (control). Binding of these molecules targeted Trp168, Asn171, Arg196, Cys237, Ser240, Trp242, Glu325, Ser326, and Cys328 residues and may affect the function of I7L protease in in vitro assay. Moreover, molecular simulation revealed stable dynamics, tighter structural packing and less flexible behaviour for all the complexes. We further reported that the average hydrogen bonds in TCM27763, TCM33057, TCM34450 and TCM31564I7L complexes remained higher than the control drug. Finally, the BF energy results revealed -62.60 ± 0.65 for the controlI7L complex, for the TCM27763I7L complex -71.92 ± 0.70 kcal/mol, for the TCM33057I7L complex the BF energy was -70.94 ± 0.70 kcal/mol, for the TCM34450I7L the BF energy was -69.94 ± 0.85 kcal/mol while for the TCM31564I7L complex the BF energy was calculated to be -69.16 ± 0.80 kcal/mol. Although, we used stateoftheart computational methods, these are theoretical insights that need further experimental validation.

[Ferroptosis is involved in testicular injury induced by TDCIPP in adolescent male mice].

Objective: To investigate the role of ferroptosis in testicular injury in adolescent male mice induced by TDCIPP. Methods: In December 2021, 30 healthy 3-week-old male C57BL/6 mice, with a body weight of (13±2) g, were selected and fed adaptive for one week. They were divided into control group, low-dose group, medium-dose group, high-dose group and iron death inhibitor group according to a random number table, with 6 mice in each group. Mice in low, medium and high dose groups were treated with 5, 25 and 125 mg/ (kg·d) TDCIPP for 28 days, respectively, while the control group was treated with the same amount of corn oil for 28 days. The iron death inhibitor group was given 125 mg/ (kg·d) TDCIPP intragastric administration for 28 days, and 30 mg/kg DFO saline solution was intraperitoneally injected three times a week. After the treatment, the mice were killed, the epididymis was separated, and sperm count was performed. HE staining was used to observe the morphological changes of mouse testis, and iron content in testis was detected by tissue iron detection kit. The level of reactive cxygen species, MDA content, and the mitochondrial membrane potential level of mice were detected. Western blot analysis of testicular glutathione peroxidase (GPX4) and internal cyclooxygenase-2 (COX2) protein expression. Results: Compared with the control group, the spermatogenic cells in the testes of mice treated with medium-and high-dose of TDCIPP were disorderly arranged, showing a vacuolar structure. the number of sperm in the epididymis was significantly reduced (P=0.009, 0.004), while the sperm deformity rate was significantly increased (P=0.010, 0.000). Moreover, the content of ROS, iron ion and MDA in the testes increased significantly (P<0.05), and the mitochondrial membrane potential of mouse testicular cells decreased significantly (P<0.05). The expression of GPX4 proteins decreased (P<0.05). while the expression of COX2 increased significantly (P<0.01). Compared with high-dose group group, spermatogenic cells in ferroptosis inhibitor group were closely arranged and normal, and ROS and Fe contents in testicular tissue were significantly decreased (P<0.01) ; GPX4 protein expression was significantly increased while COX2 protein expression was significantly decreased (P<0.05) . Conclusion: Ferroptosis is involved in TDCIPP-induced testicular damage in male pubertal mice.

[Comparative analysis of clinical diagnosis and treatment guidelines for drug-induced liver injury at home and abroad].

Drug-induced liver injury influencing factors are complex and have diverse clinical manifestations. Simple and reliable diagnostic methods are still deficient, and further classification of toxicological mechanisms is required. There are numerous pertinent discrepancies between domestic and international guidelines aimed at drug-induced liver injury diagnosis and treatment, with partial to no consensus on the content. The American Gastroenterological Association's 2021 Clinical Guidelines, the Asia-Pacific Association for the Study of the Liver's 2021 Consensus Guidelines, the Council for International Organizations of Medical Sciences' 2020 International Consensus, the European Society's Hepatology Committee's 2019 Clinical Practice Guidelines, and the 2015 Chinese Medical Association Guidelines are five influential clinical guidelines on drug-induced liver injury at home and abroad. The epidemiology, risk factors, diagnosis and evaluation, treatment management, and other contents, particularly traditional Chinese medicine, were compared and analyzed using other relevant consensus opinions or guidelines in order to improve understanding and provide a reference for clinical diagnosis and treatment of drug-induced liver injury.

[Whole-course management strategies for gastroesophageal reflux disease: an evidence mapping study based on clinical practice guidelines].

Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases with high incidence, complicated clinical symptoms, difficulties in standard treatment, and heavy medical burden. At present, some GERD-relevant clinical practice guidelines (CPGs) have been issued by different countries and academic organizations, but some recommendations were inconsistent, which has caused some problems for the current clinical whole-course management of GERD. To summarize the relevant evidence among the CPGs on GERD and formulate the whole- course management strategies, we included GERD-relevant CPGs published or updated after 2010 by searching websites of guidelines, relevant professional societies, and electronic databases. We extracted the recommendations and summarized the evidence from the aspects of symptoms, epidemiology, diagnosis and treatment, which was presented in the form of evidence mapping. We included 24 CPGs, including three in Chinese and 21 in English. The clinical practice management strategies of GERD were formulated based on the evidence from the aspects of clinical symptoms, diagnostic methods, medical treatment, anti-reflux surgery and endoscopic treatment, psychological treatment, and traditional Chinese medicine treatment.

Current management of subarachnoid hemorrhage in a northern urban Chinese population: a multi-center surveillance study.

OBJECTIVE: The current management of subarachnoid hemorrhage (SAH) in the urban Chinese population remains unclear and the relevant literature is still lacking. Therefore, this work aimed to investigate the recent clinical practice in the management of spontaneous SAH in an urban population-based setting. PATIENTS AND METHODS: From 2009 to 2011, the China Epidemiology Research In Subarachnoid Hemorrhage (CHERISH) project, which was a two-year prospective, multi-center, population-based, case-control study, was performed in the northern urban Chinese population. SAH cases were described in terms of their features, clinical management, and in-hospital outcomes. RESULTS: Totally of 226 cases were enrolled with a final diagnosis of primary spontaneous SAH (65% of females; mean age, 58.5±13.2 years; range, 20-87 years). Among them, 92% of these patients received nimodipine, while 93% took mannitol. Meanwhile, 40% of them received traditional Chinese medicine (TCM), while 43% took neuroprotective agents. Endovascular coiling was applied in 26% of 98 angiography-confirmed intracranial aneurysms (IA) cases, while neurosurgical clipping was in 5% of them. CONCLUSIONS: Our findings on the management of SAH in the northern metropolitan Chinese population reveal that nimodipine is an effective medical therapy with a high rate of use. There is also a high utilization rate of alternative medical interventions. Endovascular coiling occlusion is more common than neurosurgical clipping. Therefore, regionally traditional therapy may be a key factor for the difference in the treatment of SAH between northern and southern China.

[An investigation on the nutritional status and support of in-patients with common variable immunodeficiency].

The study aimed to reveal for the first time the clinical characteristics, nutritional and metabolic status and support of hospitalized patients with common variant immunodeficiency disease (CVID), and provide reference to improve the long-term nutritional management for such patients. This is a retrospective cross-sectional study. Through searching the electronic medical record system of Peking Union Medical College Hospital, the study included 33 consecutive in-patients with CVID diagnosed in Jan 2016 to Jun 2021, with the male to female ratio of 16∶17. All their medical data, nutritional assessment and intervention retrospectively summarized and analyzed. Data with normal distribution were described using (x¯±s), and analyzed with independent sample t-test. Data with non-normal distribution were compared with non-parametric test. The results showed that the median onset-age of the included patients was 22 (10.0,36.5) years old, and the median duration was 9.0 (2.0,16.0) years. All patients had recurrent infections involving various systems (33/33), with development of autoimmune diseases (8/33) and lymphoproliferative disease or malignancy (9/33) in some cases among them. The nutritional risk screening 2002 (NRS 2002) scores revealed that 85.19% of adults had an NRS 2002≥3 points, and 33.33% of children had a BMI-for-age z score<-2. Weight loss occurred in 66.67% of patients (22/33), while 87.88% (29/33), 69.70% (23/33) and 81.82% (27/33) of patients respectively had anemia, hypoalbuminemia and decreased prealbumin. Among 22 patients with micronutrients status evaluated, 77.27% (17/22), 22.73% (5/22) and 31.82% (7/22) of patients respectively had lowered serum iron, folate deficiency and vitamin B12 insufficiency. Six patients underwent 25-OH-VD3 measurement, and were all testified to have vitamin D deficiency. Among all patients with nutritional risk, 56.00% of them underwent nutritional support: oral nutritional supplements (14 cases), enteral feeding (4 cases) and parenteral nutrition (5 cases). In conclusion, the condition of malnutrition was prevalent in patients with CVID, but was under-recognized and undertreated to some degree.

[The status and significance of Paracelsus in the Modern Medical Revolution].

Paracelsus, the first person in the history of modern Western medicine, specified to break the shackles of the traditional medical system thoroughly and revolutionise the classical medical system completely. He introduced traditional alchemy into medicine, and changed it from making gold into producing drugs which were helpful to human health. He believed that nature and human were made by God with "three principles" - sulphur, salt and hydrargyrum. He also believed that human body, as a "chemical system", was full of a variety of chemical reactions. His ideas brought a new worldview, a chemical one, to the medical field influenced by the concept of"Humorism" for ages. The chemical worldview laid the foundation for "iatrochemistry" and channelled a path for the following medical development. The "three principles" of Paracelsus did not surpass the "Humorism" proposed by Galen in terms of underlining the balance of human health. However, the idea, that the mineral substances in nature in the "three principles" could be taken as medicines to help the recovery of human body, broke through the traditional medical system proposed by Galen, offered valuable ideological resources and experience for the following expansion and development of medicines.

[The history of post-anesthesia care units].

Post anesthesia care units (PACU) are designed to handle the utilization of the operating rooms and provide a place for postoperative patients to recover consciousness. PACU first appeared in the 1940s, prevailed in the United States in the 1950s, and expanded gradually to Canada, South Africa and other places, and were popularized in the UK and other European countries in the 1960s. PACU were developed widely in China after 1990 and expanded rapidly after the 21st century. It is now taken as an assessment indicator for evaluating hospitals. A set of management systems for PACU was gradually regulated and established, such as anesthesia record sheets, equipment and personnel training in the process of PACU development. It is currently evolving towards centralization, economization and specialization.

[Effects of different calcium intakes on metabolism in healthy adults under strict dietary intervention].

Objective: To explore the effect of different calcium intakes on metabolism in healthy adults with traditional Chinese dietary pattern. Methods: A total of 64 college students (32 males and 32 females) were recruited from the School of Public Health, Harbin Medical University from September to October 2015. A prospective, randomized, double-blind, placebo-controlled trial design (RCT trial) was used to strictly control the diet of the volunteers through meal preparation, so that the background of the experimental and the control group was exactly the same. In our study, 64 healthy adults were randomly divided into two groups (calcium supplementation and control). The two groups were given the same diet every day. One group was given 400 mg/d of calcium supplementation, which was close to the recommended intake in China (800 mg/d); the other group was given pacebo, the average calcium intake was close to the average intake of Chinese (400 mg/d), calcium intervention lasted for 35 days. Serum and urine samples from pre-intervention, mid-intervention, and post-intervention were collected for metabolomics studies and detection of serum hormone levels and biochemical indicators. PCA and PLS-DA were used to compare the differences in serum and urine metabolites. After adjusting for age and BMI, the differences of hormones [parathyroid hormone, 1, 25(OH)2D3] and biochemical indicators were compared by repeated measurement variance analysis. Results: The 64 subjects were aged 23-28 years, including 32 males and 32 females. The baseline characteristics of the calcium supplementation group and the control group were balanced. The results showed that there were no significant differences in blood and urine metabolites, metabolic hormone [parathyroid hormone, 1, 25(OH)2D3] levels and biochemical indicators(serum Ca, serum P, glycolipid metabolism and hepatorenal function indicators)between the calcium supplementation group and control group at each time point throughout the trail (P>0.05). Conclusion: No health hazards associated with calcium deficiency was observed in healthy adults in the short term at current calcium intake level (300-400 mg/d).

Enhanced retinoid response by a combination of the vitamin A ester retinyl propionate with niacinamide and a flavonoid containing Ceratonia siliqua extract in retinoid responsive in vitro models.

OBJECTIVES: Retinoids have been used for decades as efficacious topical agents to treat photoaged skin. The purpose of our present research is to evaluate whether the activity of the vitamin A ester retinyl propionate (RP) can be enhanced by niacinamide (Nam) and a flavonoid containing Ceratonia siliqua (CS) fruit extract in retinoid responsive in vitro models. METHODS: Retinyl propionate was tested alone and in combination with Nam and CS in an RARα reporter cell line for promoter activation and compared to trans-retinoic acid (tRA) activation. These treatments were also tested in keratinocytes for gene expression profiling by qPCR using a panel of 40 retinoid responsive genes. RESULTS: tRA or RP elicited RARα reporter activation in a dose-dependent manner. The combination of 0.5 µM or 2 µM RP with 10 mM Nam had a 56% and 95% signal increase compared to RP, respectively. The addition of 1% CS to 0.5 µM or 2 µM RP with 10 mM Nam elicited a further increase of 114% and 156%, respectively, over RP and Nam combinations. All retinoids elicited an increase in expression of 40 retinoid sensitive genes over control levels. Of the 40 genes, 27 were enhanced by either 0.1 µM RP or 0.5 µM RP with 10 mM Nam and 1% CS. Nam or CS had very modest activity in both models. CONCLUSION: The combination of RP with Nam and CS showed a higher retinoid response than RP in two separate retinoid responsive in vitro models. We hypothesize Nam and CS enhances RP activity by modulating metabolism to tRA via increasing NAD+ pools and inhibiting reduction of retinal (RAL) back to retinol, respectively. The findings provide evidence that this combination may have enhanced efficacy for treating the appearance of photoaged skin.

OBJECTIFS: Les rétinoïdes sont utilisés depuis des décennies comme agents topiques efficaces pour traiter la peau photo-âgée. Le but de notre recherche actuelle est d'évaluer si l'activité du propionate rétinyl ester de vitamine A (RP) peut être augmentée par le niacinamide (Nam) et un flavonoïde contenant un extrait de fruit de Ceratonia Siliqua (CS) dans les modèles in vitro sensibles aux rétinoïdes. MÉTHODES: RP a été testé seul et en combinaison avec Nam et CS dans une ligne de cellule rapporteur de RARα pour l'activation du promoteur et par rapport à l'activation de l'acide transrétinoïque(tRA). Ces traitements ont également été testés dans les kératinocytes pour le profilage d'expression génique par qPCR à l'aide d'un panel de 40 gènes rétinoïdes sensibles. RÉSULTATS: tRA ou RP ont provoqué l'activation du promoteur RARα d'une manière dépendante de la dose. La combinaison de 0,5 µM ou 2 µM de RP avec 10 mM de Nam a permis une augmentation respectivement de 56% et 95% du signal par rapport à RP. L'ajout de 1 % de CS à 0,5 µM ou 2 µM de RP avec 10 mM de Nam a permis une nouvelle augmentation de 114 % et 156 %, respectivement, qu'avec la combinaison RP et Nam. Tous les rétinoïdes ont provoqué une augmentation de l'expression de 40 gènes sensibles aux rétinoïdes sur les niveaux de contrôle. Sur les 40 gènes, 27 ont été améliorés soit par 0,1 µM de RP ou 0.5 µM de RP avec 10 mM de Nam et 1% de CS. Nam ou CS avaient une activité très modeste dans les deux modèles. CONCLUSION: La combinaison de RP avec Nam et CS a montré une réponse rétinoïde plus élevée que RP dans deux modèles in vitro séparés sensibles aux rétinoïdes. Nous émettons l'hypothèse que Nam et CS améliorent l'activité RP en modulant le métabolisme de tRA par l'augmentation des groupement NAD+ et en inhibant la réduction du rétinal (RAL) en rétinol, respectivement. Les résultats fournissent la preuve que cette combinaison peut améliorer l'efficacité du traitement de l'aspect de la peau photo-âgée.

JTE-013 supplementation improves erectile dysfunction in rats with streptozotocin-induced type â diabetes through the inhibition of the rho-kinase pathway, fibrosis, and apoptosis.

BACKGROUND: Erectile dysfunction (ED) is a common complication in patients with diabetes mellitus (DM) that severely affects the patients' quality of life. However, the effectiveness of oral phosphodiesterase type 5 inhibitors in these patients is poor. Sphingosine-1-phosphate (S1P) and S1P receptor 2 (S1PR2) are important factors regulating the Rho-kinase pathway, and understanding these factors may provide ideas for new therapeutic strategies for ED. OBJECTIVES: To investigate whether the S1PR2 receptor antagonist JTE-013 could improve DM-induced ED (DMED) in rats and to explore the potential mechanisms. MATERIALS AND METHODS: We used 50 male Sprague Dawley rats (8 weeks old) for this experiment. Type Ⅰ DM was induced in forty-two rats via streptozotocin administration; the rest of the rats served as controls. Eight weeks after DM induction, rats with ED were selected via an apomorphine test. Eight of them were injected intraperitoneally with JTE-013 each day for 4 weeks. The rest were fed under the same conditions for 4 weeks. Erectile function was measured by cavernous nerve electrostimulation. The expression levels of related signaling pathways were evaluated using Western blotting, real-time PCR, and immunohistochemistry. RESULTS: Erectile function was significantly impaired in the DMED group compared with the control group and was partially improved in the DMED + JTE-013 group. The expression of S1PR2 and the activity of the RhoA/ROCK/phospho-myosin phosphatase target subunit 1 (p-MYPT1) pathway proteins were higher in the DMED group than in the other two groups, and JTE-013 treatment significantly reduced the expression/activity of these proteins. Furthermore, the DMED group showed severe corporal fibrosis, a higher apoptotic index and increased activity in the TGF-ß1/LIMK2/Cofilin pathway compared with the control group. JTE-013 supplementation significantly ameliorated these pathological changes. DISCUSSION AND CONCLUSION: JTE-013 supplementation partially improved erectile function in rats with DMED, likely by inhibiting smooth muscle contraction, corporal fibrosis, and apoptosis.

[Association between dietary supplementation during pregnancy and low birth weight: a prospective study].

Objective: To explore the association between dietary supplementation during pregnancy and low birth weight. Methods: 11 311 pregnant women who had regularly visited outpatient gynecology clinic of Wuhan Women and Children Medical Center with intention to delivery in the hospital were recruited in the cohort between September 2012 and October 2014. Social-demographic characteristics of pregnant women and spouses, dietary supplementation during pregnancy, pre-pregnancy body mass index (BMI), exercise in the third trimester, work during pregnancy, pregnancy complications and related pregnancy information were collected through self-designed questionnaires, maternal health manuals and medical records. Birth weight of the newborns was measured. Non-conditional multivariate logistic regression analysis was used to determine the correlation between dietary supplementation and low birth weight. Results: 11 311 pregnant women were (28.21±3.70) years old, and they gave birth to 477 low birth weight newborns (4.2%). Iron supplementation during the whole period of pregnancy (OR (95%CI): 0.60 (0.43-0.63)) and folic acid supplementation during the early pregnancy (OR (95%CI): 0.74 (0.60-0.90)) were negatively associated with low birth weight. Conclusion: Supplementation of iron during the whole period of pregnancy and folic acid during the early pregnancy would reduce the risk of low birth weight.

Attenuating effect of melatonin on lipopolysaccharide-induced chicken small intestine inflammation.

Enriched melatonin (MEL) has been found in the mammalian intestine and has been recently demonstrated to alleviate rodent colitis. In this study, the effect of MEL on lipopolysaccharide (LPS)-induced intestinal inflammations was investigated in new chicken hatchlings. The chicks were fed with a diet supplemented with MEL (12.5 mg/day) from D1 to D10. Meanwhile, the chicks in the LPS or MEL + LPS groups were injected with LPS (10 mg/kg BW, i.p.) at D10. LPS treatment for 6 h increased the expression of IL-6, IL-4, caspase-3 mRNAs and TUNEL-positive cell populations, but decreased populations of the goblet and PCNA+ cells, IgA production and the expression of MUC2 mRNA in the duodenum. Compared with the LPS group, MEL pre-feeding alleviated duodenal inflammation and decreased the expression of TNF-α mRNAs by 23.6% (P = 0.004), IL-6 mRNAs by 69.4% (P = 0.001), IL-4 mRNAs by 4.1% (P = 0.824) and caspase-3 mRNAs by 45.8% (P < 0.001). Conversely, MEL pre-feeding attenuated the LPS-induced changes of IgA production by 161.6% (P = 0.013) and PCNA+ cell populations by 172.1% (P < 0.001) in the duodenum. TLR4 mRNA was also up-regulated by LPS treatment but down-regulated by MEL pre-feeding. In conclusion, dietary MEL could attenuate LPS-induced chick duodenal inflammation by down-regulating the expression of inflammatory cytokines, promoting epithelial cell proliferation, improving the immunological barrier and inhibiting epithelial apoptosis via the mediation of TLR4.

A comparison of two sources of methionine supplemented at different levels on heat shock protein 70 expression and oxidative stress product of Peking ducks subjected to heat stress.

The aim of this study was to examine the effects of different sources and levels of methionine (Met) on Heat shock proteins HSP70 expression and protein carbonylation in liver, HSP70 expression and malondialdehyde (MDA) concentration in intestine under heat stress conditions during summer. A total of 720 (4 days old) Peking ducks were placed 20 per pen into six replicates for each of the six treatments with a 2 × 3 factorial arrangement, such that two sources of Met (DL-methionine [DLM] and DL-2-hydroxy-4-methylthiobutyrate [HMTBA] were supplemented at three different levels (0.05%, 0.20%, or 0.35% on as-fed basis respectively). The experiment was divided into a starter (day 4-16) and a grower (day 17-35) period. Diet supplemented with 0.35% Met significantly up-regulated the HSP70 mRNA expression in duodenum, jejunum and ileum on day 16 and 35 as well as in liver on day 35 (p < .05) of ducks. HMTBA-supplemented diets increased the HSP70 mRNA expression in duodenum, jejunum, ileum and liver on day 35 (p < .01). An increased MDA concentration was detected in jejunum of birds in 0.35% DLM-supplemented treatment on day 16 (p < .05). And decreased protein carbonylation concentration was found in DLM-supplemented treatment on day 16 (p < .01). The birds fed with 0.35% Met supplemental diet displayed lower hepatic protein carbonylation on day 16 (p < .05). In conclusion, supplementation of 0.35% Met in the duck diet showed up-regulated HSP70 expression in small intestine and liver, which may provide new perspective to the mechanism of Met function. At the same time, DLM supplemented in diet may ameliorate oxidative status of liver, while HMTBA supplementation may partially improve the intestinal oxidative status of Peking ducks.

DNMT3A-mediated down-regulation of microRNA-105 promotes gastric cancer cell proliferation.

OBJECTIVE: It has been well-established that microRNAs (miRNAs), a class of short non-coding RNA molecules, play an important role in the development of gastric cancer. In the present study, we focused on miR-105, a novel miRNA not previously linked to gastric cancer. PATIENTS AND METHODS: 36 paired surgically resected gastric cancer tissues and matched adjacent normal tissues were used to detect the expression of miR-105. AGS cells were used to overexpress or silence of miR-105 and to determine its effect on several tumorigenic properties. A cell proliferation enzyme-linked immunosorbent assay was used to analyze the incorporation of BrdU during DNA synthesis of AGS cells. Total cDNA from AGS cells was used to amplify the 3'-UTR of YY1 by PCR and luciferase activity was determined using the Dual-Luciferase Reporter Assay System RESULTS: We found that expression of miR-105 was reduced in gastric cancer tissues, compared with adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-105 suppressed, whereas its inhibition promoted cell viability and proliferation. We further identified Yin Yang 1 (YY1) as a direct target of miR-105, by which miR-105 exerted its anti-proliferative role. Moreover, we found that DNMT3A was responsible for the down-regulation of miR-105 in gastric cancer cells. CONCLUSIONS: Our data demonstrate that miR-105 inhibits gastric cancer cell proliferation and progression, which might provide a therapeutical target for cancer therapy.

Lysolecithin as feed additive enhances collagen expression and villus length in the jejunum of broiler chickens.

Adding lysolecithin to feed has reportedly improved the performance of broiler chickens. Lysolecithin is generated by phospholipase catalyzed hydrolysis of lecithin. The enzymatic reaction converts various phospholipids into the corresponding lysophospholipids, with lysophosphatidylcholine (LPC) one of the primary products. Here we compared supplementation with a commercial lysolecithin (Lysoforte®) with comparable levels of highly purified LPC for effects on broilers. Despite no differences in weight gain during the starter period, we discovered a significant increase in average villus length with lysolecithin and an increase in villus width with purified LPC. High-throughput gene expression microarray analyses revealed many more genes were regulated in the epithelium of the jejunum by lysolecithin compared to purified LPC. The most up-regulated genes and pathways were for collagen, extracellular matrix, and integrins. Staining sections of the jejunum with Picrosirius Red confirmed the increased deposition of collagen fibrils in the villi of broilers fed lysolecithin, but not purified LPC. Thus, lysolecithin elicits gene expression in the intestinal epithelium, leading to enhanced collagen deposition and villus length. Purified LPC alone as a supplement does not mimic these responses. Feed supplementation with lysolecithin triggers changes in the intestinal epithelium with the potential to improve overall gut health and performance.

Experimental study on 1,25(OH)2 D3 amelioration of oral lichen planus through regulating NF-κB signaling pathway.

OBJECTIVE: To explore the protective function of vitamin D (VD)/vitamin D receptor (VDR) on the development of oral lichen planus (OLP) and elaborate the underling mechanism of it. METHODS: H&E staining, myeloid peroxidase (MPO) assays, quantitative PCR (qPCR), Western blotting, and Elisa were used to test the human biopsies and serum. QPCR, Western blotting, Elisa, and siRNA transfection were also performed in LPS-induced keratinocytes to observe the functions of vitamin D and VDR. RESULTS: The lack of VDR in the diseased biopsies from OLP patients was associated with activated helper T-cell type 1 (Th1)-driven inflammatory response. Importantly, the status of serum 25-hydroxyvitamin D of OLP patients was reduced consistently. In a cultured cell model, 1,25(OH)2 D3 could downregulate excessive production of pro-inflammatory factors induced by lipopolysaccharide (LPS) in keratinocyte HaCat cells. Mechanistically, even though LPS-induced cytokines in keratinocytes were inhibited both by nuclear factor-κB (NF-κB) inhibitor and by activator protein 1 (AP-1) inhibitor, VDR-dependent 1,25(OH)2 D3 blocked the activation of phosphorylated-NF-κB p65 rather than c-Jun/c-Fos in the presence of LPS stimulation. CONCLUSION: These results suggest that 1,25(OH)2 D3 plays an anti-inflammatory role in OLP by mediating NF-κB signaling pathway but not AP-1 signaling pathway with a VDR-dependent manner, predicting vitamin D supplement may be a potential strategy for the OLP management.

Hyperlipidemia impairs erectile function in rats by causing cavernosal fibrosis.

Men with hyperlipidemia are more likely to have erectile dysfunction (ED) than those without hyperlipidemia, but the mechanisms are not fully understood. The aim of this study was to investigate the underlying mechanism of ED caused by hyperlipidemia. Fourteen 8-week-old Sprague-Dawley rats were randomly divided into two groups: a control group and a hyperlipidemia group (fed chow containing 4% cholesterol and 1% cholic acid). After 6 months, we assessed erectile function by performing cavernous nerve electrostimulation followed by intracavernosal pressure/mean arterial pressure measurements, as well as plasma lipid profile assessment in all rats. A transferase-mediated nick end labeling (TUNEL) assay, immunohistochemical staining and Western blotting were performed to determine the levels of apoptosis, autophagy and fibrosis in the penile tissue. Compared with the control group, the hyperlipidemia group exhibited: (i) increased plasma lipid levels; (ii) decreased erectile function; (iii) a decreased smooth muscle/collagen ratio; (iv) increased fibrosis; (v) increased apoptosis and decreased autophagy. Overall, hyperlipidemia may attenuate erectile function in rats by causing of cavernosal fibrosis.