Therapeutic effects of hederacolchiside A1 on particulate matter-induced pulmonary injury.

Particulate matter (PM) comprises a hazardous mixture of inorganic and organic particles that carry health risks. Inhaling fine PM particles with a diameter of ≤2.5 µm (PM2.5) can promote significant lung damage. Hederacolchiside A1 (HA1) exhibits notable in vivo antitumor effects against various solid tumors. However, our understanding of its therapeutic potential for individuals with PM2.5-induced lung injuries remains limited. Here, we explored the protective properties of HA1 against lung damage caused by PM2.5 exposure. HA1 was administered to the mice 30 min after intratracheal tail vein injection of PM2.5. Various parameters, such as changes in lung tissue wet/dry (W/D) weight ratio, total protein/total cell ratio, lymphocyte counts, inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF), vascular permeability, and histology, were assessed in mice exposed to PM2.5. Our data showed that HA1 mitigated lung damage, reduced the W/D weight ratio, and suppressed hyperpermeability caused by PM2.5 exposure. Moreover, HA1 effectively decreased plasma levels of inflammatory cytokines in those exposed to PM2.5, including tumor necrosis factor-α, interleukin-1ß, and nitric oxide, while also lowering the total protein concentration in BALF and successfully alleviating PM2.5-induced lymphocytosis. Furthermore, HA1 significantly decreased the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation primary response (MyD) 88, and autophagy-related proteins LC3 II and Beclin 1 but increased the protein phosphorylation of the mammalian target of rapamycin (mTOR). The anti-inflammatory characteristics of HA1 highlights its potential as a promising therapeutic agent for mitigating PM2.5-induced lung injuries by modulating the TLR4-MyD88 and mTOR-autophagy pathways.

Steamed Ginseng Berry Powder Ameliorates Skeletal Muscle Atrophy via Myogenic Effects.

Sarcopenia is an age-related loss of muscle mass and function for which there is no approved pharmacological treatment. We tested direct efficacy by evaluating grip strength improvement in a sarcopenia mouse model rather than drug screening, which inhibits specific molecular mechanisms. Various physiological functions of ginseng berries are beneficial to the human body. The present study aimed to evaluate the efficacy and safety of steamed ginseng berry powder (SGBP). SGBP administration increased myotube diameter and suppressed the mRNA expression of sarcopenia-inducing molecules. SGBP also reduced the levels of inflammatory transcription factors and cytokines that are known to induce sarcopenia. Oral administration of SGBP improved muscle mass and physical performance in a mouse model of sarcopenia. In summary, our data suggest that SGBP is a novel therapeutic candidate for the amelioration of muscle weakness, including sarcopenia.

Exploration on Optimizing "Five-sphere" Medical Humanistic Care Service in Medical and Nursing Institutions / 中国医学伦理学

The combination of medical care and nursing is an important measure of health care for the aged, and it is also an important part of aging work. Under the background of increasing aging, and under the background of changing from disease-centered and patient-centered medical model to health-centered "big medicine" model, medical humanities are particularly important for how to make the elderly spend their old age in peace and make the road of combining medical care with nursing care wider. Based on the practice of combination of medical care and nursing, under the guidance of the concept of great health, this paper discussed the establishment of a "Five-sphere" all-round humanistic care concept integrating medical care, nutrition care, sports care, mental care and other convalescent health care factors, and provided a series of comprehensive multi-angle humanistic care service measures from physiology to psychology for elderly patients with chronic diseases, which has achieved good results.

Myogenesis Effects of RGX365 to Improve Skeletal Muscle Atrophy.

Age-related skeletal muscle atrophy and weakness not only reduce the quality of life of those afflicted, but also worsen the prognosis of underlying diseases. We evaluated the effect of RGX365, a protopanaxatriol-type rare ginsenoside mixture, on improving skeletal muscle atrophy. We investigated the myogenic effect of RGX365 on mouse myoblast cells (C2C12) and dexamethasone (10 µM)-induced atrophy of differentiated C2C12. RGX365-treated myotube diameters and myosin heavy chain (MyHC) expression levels were analyzed using immunofluorescence. We evaluated the myogenic effects of RGX365 in aging sarcopenic mice. RGX365 increased myoblast differentiation and MyHC expression, and attenuated the muscle atrophy-inducing F-box (Atrogin-1) and muscle RING finger 1 (MuRF1) expression. Notably, one month of oral administration of RGX365 to 23-month-old sarcopenic mice improved muscle fiber size and the expression of skeletal muscle regeneration-associated molecules. In conclusion, rare ginsenosides, agonists of steroid receptors, can ameliorate skeletal muscle atrophy during long-term administration.

Benefit of Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy and Bidirectional Chemotherapy for Patients with Gastric Cancer with Peritoneal Carcinomatosis Considering Cytoreductive Surgery.

Comprehensive treatment comprising neoadjuvant laparoscopic HIPEC (L-HIPEC) and bidirectional intraperitoneal and systemic induction chemotherapy (BISIC) followed by cytoreductive surgery (CRS) for gastric cancer with peritoneal carcinomatosis (PC) has been developed. However, its benefits and patient selection criteria have not been thoroughly investigated. We retrospectively reviewed 113 patients, with 25 having received comprehensive treatment (L-HIPEC, BISIC, and then CRS-HIPEC; the BISIC group) and 88 having received direct CRS-HIPEC (the CRS group). The BISIC group showed greater tumor clearance in terms of post-CRS peritoneal cancer index ((PCI) 6 vs. 14, p = 0.002) compared to CRS group. The median survival was 20.0 months in the BISIC group and 8.6 months in the CRS group (p = 0.031). Multivariable analysis revealed that the factors associated with increased survival were the BISIC protocol, age, and post-CRS tumor clearance. BISIC significantly improved survival in cases of moderate severity (PCI 11-20) and severe cases (PCI 21-39) without increasing the morbidity rate. We recommend the use of this neoadjuvant strategy for patients with gastric cancer-associated PC and an initial PCI of >10 to provide superior survival outcomes.

Effect of modifying negative interpretation bias toward ambiguous social stimuli across eating and personality disorders.

OBJECTIVE: Heightened sensitivity toward social rejection has been implicated in eating disorders (ED) and personality disorder (PD). This study examined the effect of a cognitive bias modification training (CBM-I) targeting the interpretation of ambiguous social situations in individuals with comorbid ED and PD. METHOD: A total of 128 participants [33 with ED and PD, 22 with ED-only, 22 with PD-only, and 51 healthy controls (HC)] were recruited from a hospital and university settings, and included in the final analyses. The participants were randomly assigned to a CBM-I task with benign resolutions or a control task with neutral resolutions in a counterbalanced order in two sessions using a within-subject design. Interpretation bias toward social stimuli was measured using the ambiguous sentence completion task before and after completing the assigned task. RESULTS: The CBM-I task increased benign and decreased negative interpretations with large effect sizes in the diagnostic groups, and with a moderate effect size in the HC group. Participants' anxiety levels were also reduced after the task. The size of the change in negative interpretation was positively associated with baseline negative affect, and negatively associated with baseline positive affect. DISCUSSION: The results suggest that modifying interpretation bias has the potential as a transdiagnostic target of treatment for ED and PD, and a fully powered clinical trial with consecutive sessions would be warranted. PUBLIC SIGNIFICANCE: Participants with eating disorders and/or personality disorder, and healthy controls completed a single session of a cognitive training intervention targeting rejection sensitivity. The training produced a large decrease in negative interpretation in the diagnostic groups, and a moderate effect in healthy controls. The findings indicate that training for positive processing of social information may be of value to augment treatment in conditions such as eating disorders and personality disorder, in which there are high levels of rejection sensitivity.

Theoretical study on the mechanism of water oxidation catalyzed by a mononuclear copper complex: important roles of a redox non-innocent ligand and HPO4 2- anion.

The water oxidation reaction is the bottleneck problem of the artificial photosynthetic system. In this work, the mechanism of water oxidation catalyzed by a mononuclear copper complex in alkaline conditions was studied by density functional calculations. Firstly, a water molecule coordinating with the copper center of the complex (Cuii, 1) generates Cuii-H2O (2). 2 undergoes two proton-coupled electron transfer processes to produce intermediate (4). The oxidation process occurs mainly on the ligand moiety, and 4 (˙L-Cuii-O˙) can be described as a Cuii center interacting with a ligand radical antiferromagnetically and an oxyl radical ferromagnetically. 4 is the active species that can trigger O-O bond formation via the water nucleophilic attack mechanism. This process occurs in a step-wise manner. The attacking water transfers one of the protons to the HPO4 2- coupled with an electron transfer to the ligand radical, which generates a transient OH˙ interacting with the oxyl radical and H2PO4 -. Then the O-O bond is formed through the direct coupling of the oxo radical and the OH radical. The triplet di-oxygen could be released after two oxidation processes. According to the Gibbs free energy diagram, the O-O bond formation was suggested to be the rate-limiting step with a calculated total barrier of 19.5 kcal mol-1. More importantly, the copper complex catalyzing water oxidation with the help of a redox non-innocent ligand and HPO4 2- was emphasized.

Hederacolchiside A1 Suppresses Autophagy by Inhibiting Cathepsin C and Reduces the Growth of Colon Cancer.

While autophagy degrades non-functional or unnecessary cellular components, producing materials for synthesizing cellular components, it can also provide energy for tumor development. Hederacolchiside A1 (HA1) derived from anemone raddeana has anticancer effects on several carcinomas by inducing apoptosis or exhibiting cytotoxicity, but the relationship with autophagy has not been studied. We investigated the association between HA1 and autophagy and evaluated its anticancer effect on colon cancer. HA1 induced accumulation of the autophagy-related markers LC3B and SQSTM1, with distinct vacuolar formation, unlike other autophagy inhibitors; the effects were similar to those of chloroquine. In addition, HA1 decreased the expression and proteolytic activity of lysosomal protein cathepsin C, reduced the growth of colon cancer cells in vitro, and inhibited tumor growth in vivo. It also reduced the expression of Ki-67 and cathepsin C in mouse tissues and reduced the growth of spheroids and organoids composed of cancer cells. Taken together, these results imply that HA1 regulates cell growth and autophagy and has potential as a promising therapeutic agent in colon cancer.

Analysis of Chinese Medical Syndrome Features of Ischemic Stroke Based on Similarity of Symptoms Subgroup / 中国结合医学杂志

OBJECTIVE@#To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients.@*METHODS@#By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup.@*RESULTS@#Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens.@*CONCLUSIONS@#There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.

Current situation of medical humanistic quality cultivation throughout the whole-process education of medical students under the background of "New Era" / 中华医学教育探索杂志

Objective:Under the background of "new medical science", to construct a whole-process education path with "education as the driving force - moral cultivation as the core", and to provide a decision-making basis for the reform, innovation, and development of humanistic quality education in medical colleges.Methods:Five-year clinical medical students (freshman to fifth graders) from Qiqihar Medical University were selected as the research objects. The evaluation model and questionnaire of humanistic quality of clinical medical students were constructed by literature analysis. The Questionnaire Star platform was used to investigate and collect data by random sampling of clinical medical undergraduates, and the data results were analyzed by SPSS 26.0 to explore the path of building the whole-process education.Results:The empirical research on the cultivation of humanistic quality of medical students showed that the average humanistic attitude score of medical students was (3.47±0.75) points. From the perspective of gender, the scores of humanistic cognition, attitude, and behavior of male students were 2.81, 3.68, and 3.22 points, respectively, which were all significantly higher than those of female students (2.52, 3.22, and 2.95 points, respectively) ( P<0.05). The data from freshmen to the fifth graders showed that humanistic cognition, attitude, and behavior scores all presented an increasing trend with the grade. Using the "Knowledge, Attitude/Belief, Practice" model, it was found that the cognitive rate of humanistic quality of medical students was relatively ideal, and the awareness rate of medical students in different grades was different. The cross analysis showed that the effect of ideological morality and political literacy education on medical students in medical colleges had a significant cross-relationship with multiple choice questions. Conclusion:The humanistic quality of clinical medical students needs to be improved, and the cultivation of medical humanistic quality should run through the whole process from the first year to the fifth year, so as to improve the comprehensive training of professional ability and promote the all-round development of medical students.

Practice research on improving the capability of service-based education in basic teaching organizations in colleges and universities from the perspectives of four characteristics and four abilities / 中华医学教育探索杂志

Objective:To implement the teaching activities for cultivating the four characteristics (innovation, development, integration, and ecology) and the four abilities (political ability, learning ability, cross-border ability, and driving force), and to provide a reference for improving the capability of service-based education in basic teaching organizations.Methods:The basic teaching organization in School of Basic Medical Sciences, Qiqihar Medical University, was selected for research, and the action research method and the focus group interview method were used to carry out characteristic teaching activities around the cultivation of the four characteristics and the four abilities. After the implementation of these activities, Sojump, a questionnaire platform, was used to conduct a survey among full-time and part-time teachers and teaching administrators, and the effect of each activity on the cultivation of the four characteristics and the four abilities was analyzed. The strategies to enhance abilities were improved based on the results of the above analyses. SPSS 25.0 software was used for data processing, and categorical data were expressed as frequency and percentage.Results:The data analysis showed that through cultivation of the four characteristics and the four abilities, each designed activity had a remarkable effect on improving the capability of service-based education in the basic teaching organization, with a mean value of 80.77%(63/78)- 91.03%(71/78), and only the activities centered on "integration" had a relatively low value of "obvious effect", which accounted for 64.10%(50/78).Conclusion:Under the guidance of the new concept of "New Medicine" and with the opportunity of capacity building, a series of teaching activities focusing on the four characteristics and the four abilities can effectively improve the capability of service-based education in basic teaching organizations in colleges and universities through targeted ability training.

Effects of paternal age on pregnancy outcomes in frozen-thaw embryo transfer cycles / 现代泌尿外科杂志

【Objective】 To observe the effects of paternal age on the pregnancy outcomes in frozen embryo transfer (FET) cycles. 【Methods】 The clinical data of two groups after propensity score matching (PSM) were retrospectively analyzed, including 738 cycles in the 0.05). The clinical pregnancy rate (52.2%vs. 67.2%) and live birth rate (41.1% vs. 57.2%) decreased in the 40-60 year group compared with those in the 0.05). 【Conclusion】 Advanced paternal age decreases clinical pregnancy rate and live birth rate.

Ameliorative Effect of Ginsenoside Rg6 in Periodontal Tissue Inflammation and Recovering Damaged Alveolar Bone.

Periodontal disease is a chronic disease with a high prevalence, and in order to secure natural materials to prevent oral diseases, new materials that protect periodontal tissue from inflammation are being sought. Genes were identified using real-time quantitative polymerase chain reaction (RT-qPCR), and proteins were confirmed using Western blot. Dichlorodihydrofluorescein diacetate (DCF-DA) analysis was used, and the antibacterial effects were confirmed through Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) analysis. To confirm this effect in vivo, Sprague-Dawley rats, in which periodontitis was induced using ligation or Lipopolysaccharide of Porphyromonas gingivalis (PG-LPS), were used. In vitro experiments using human periodontal ligament (HPDL) cells stimulated with PG-LPS showed that Ginsenoside Rg6 (G-Rg6) had anti-inflammatory, antibacterial, antioxidant, and osteoblast differentiation properties. In vivo, G-Rg6 was effective in Sprague-Dawley rats in which periodontitis was induced using ligation or PG-LPS. Therefore, Ginsenoside Rg6 shows potential effectiveness in alleviating periodontitis.

Evaluation of efficiency of different anti-cysticercus antibody test kits for serodiagnosis of cysticercosis / 中国血吸虫病防治杂志

Objective To evaluate the diagnostic efficiency of four anti-cysticercus IgG, IgG4 or IgM antibody test kits (enzyme-linked immunosorbent assay, ELISA) by different manufacturers, so as to provide insights into the epidemiological investigation and clinical detection of cysticercosis. Methods Forty serum samples from cerebral cysticercosis patients, 100 serum samples from healthy volunteers, 30 serum samples from paragonimiasis skrjabini patients, 17 serum samples from cystic echinococcosis and 19 serum samples from subcutaneous or cerebral sparganosis patients were collected and detected using anti-cysticercus IgG, IgG4 or IgM antibody test kits (brand A) and the anti-cysticercus IgG antibody test kit (brand B). The sensitivity, specificity and false negative rate of the four kits for detection of cysticercosis were estimated. Results The anti-cysticercus IgG, IgG4 or IgM antibody test kits (brand A) showed 95.00% (38/40), 87.50% (35/40), 7.50% (3/40) sensitivities and 98.00% (98/100), 100.00% (100/100) and 100.00% (100/100) for detection of cysticercosis, while the anti-cysticercus IgG antibody test kit (brand B) presented a 75.00% (30/40) sensitivity and 100.00% (100/100) specificity for detection of cysticercosis. The sensitivity for detection of cysticercosis was significantly higher by the anti-cysticercus IgG antibody test kit (brand A) than by the anti-cysticercus IgG antibody test kit (brand B) (χ2 = 6.28, P < 0.05); however, no significant difference was seen in the specificity by two kits (χ2 = 2.01, P > 0.05). The four ELISA kits showed overall false positive rates of 37.88% (25/66), 22.73% (15/66), 62.12% (41/66) and 15.15% (10/66) for detection of paragonimiasis, echinococcosis and sparganosis (χ2 = 37.61, P < 0.05), and the anti-cysticercus IgG antibody test kit (brand A) presented the highest overall false positive rate for detection of paragonimiasis, echinococcosis and sparganosis (χ2 = 7.56, P’ < 0.008), while a higher overall false positive rate was seen for detection of paragonimiasis, echinococcosis and sparganosis by the anti-cysticercus IgG antibody test kit (brand A) than by the anti-cysticercus IgG antibody test kit (brand B) (χ2 = 8.75, P’ < 0.008). The four ELISA kits showed false positive rates of 40.00% (12/30), 16.67% (5/30), 76.67% (23/30) and 13.33% (4/30) for detection of paragonimiasis (χ2 = 32.88, P < 0.05) and 21.05% (4/19), 26.32% (5/19), 73.68% (14/19) and 15.79% (3/19) for detection of sparganosis (χ2 = 19.97, P < 0.05), and the highest false positive rates were found by the anti-cysticercus IgM antibody test kit (brand A) for detection of paragonimiasis and sparganosis (all P’ < 0.008). However, the four ELISA kits showed comparable false positive rates of 52.94% (9/17), 29.41% (5/17), 23.53% (4/17) and 17.65% (3/17) for detection of echinococcosis (χ2 = 8.24, P > 0.05). In addition, the anti-cysticercus IgM anti-body test kit (brand A) showed false positive rates of 76.67% (23/30), 23.53% (4/17) and 73.68% (14/19) for detection of paragonimiasis, echinococcosis and sparganosis (χ2 = 14.537, P < 0.05), with the lowest false positive rate seen for detection of echinococcosis (χ2 = 14.537, P’ < 0.014), while no significant differences were seen in the false positive rate for detection of paragonimiasis, echinococcosis and sparganosis by other three ELISA kits (all P > 0.05). Conclusions The four anti-cysticercus IgG, IgG4 or IgM antibody test kits exhibit various efficiencies for serodiagnosis of cysticercosis. The anti-cysticercus IgG antibody test kit (brand A) has a high sensitivity for serodiagnosis of cysticercosis; however, it still needs to solve the problems of cross-reaction with other parasitic diseases and stability.

Research progress in clinical treatment of Alzheimer's disease and potential drugs from natural products / 药学学报

With the acceleration of the aging process of our country's population, the impact of aging-related diseases - Alzheimer's disease (AD) on society and families has become increasingly prominent. AD is caused by multiple mechanisms, and the pathogenesis has not been fully elucidated. Most of the clinical treatments are single therapy, which mainly focuses on improving symptoms and are difficult to reverse the disease process. Therefore, the development of drugs that can both improve symptoms and reverse the disease process is extremely urgent in clinical. Increasing number of studies has shown that traditional Chinese medicine plays an important role in the prevention and treatment of AD. The natural products have many advantages, such as novel structures, multiple targets and diverse activities, which can be used as an important source of leading compounds for the treatment of AD. The review summarizes the main clinical treatment methods and the research progress of natural ingredients in traditional Chinese medicine, and provides a reference for the follow-up clinical treatment of AD combined with the advantages of traditional Chinese medicine treatment.

Epidemiological investigation on a visceral leishmaniasis case in Zhengzhou City of Henan Province / 中国血吸虫病防治杂志

Objective To perform an epidemiological investigation on a case with visceral leishmaniasis in Zhengzhou City, Henan Province, and to identify the source of infection, so as to illustrate the transmission chain and assess the risk of local leishmaniasis transmission. Methods The medical data were collected from a case with visceral leishmaniasis in Zhengzhou City, and the patient’s bone marrow smears were detected by microscopy. Serum anti-Leishmania antibody test and PCR assay were performed among high-risk residents and all dogs in the village where the patient lived. Sandflies were captured using light traps and artificial traps, and the captured female Phlebotomus chinensis was subjected to PCR assay. The internal transcribed spacer 1 (ITS1) gene was amplified with a nested PCR assay using the genomic DNA extracted from visceral leishmaniasis patients, positive dogs and sandflies, and the sequences were aligned with those download from NCBI. In addition, a phylogenetic tree was created based on the ITS1 gene. Results The visceral leishmaniasis patient had recurrent irregular fever, reduced complete blood counts, low hemoglobin, and a large number of Leishmania amastigotes in bone marrow smears, and was therefore diagnosed as visceral leishmaniasis. Both rk39 rapid diagnostic test and PCR assay tested negative among 324 residents living neighboring the patient’s residence, while 21.39% (43/201) dogs were positive for rk39 rapid diagnostic test and 13.93% (28/201) positive for PCR assay. There were 17 female Ph. chinensis tested positive for Leishmania (0.82%) by PCR assay, and the ITS gene sequences from visceral leishmaniasis patients, positive dogs and sandflies shared a 100% homology with L. infantum. The Leishmania species was therefore characterized as L. infantum. Conclusions L. infantum infection occurs in visceral leishmaniasis patients, dogs and sandflies in Zhengzhou City, indicating a complete transmission chain and a high transmission risk of visceral leishmaniasis by L. infantum. Intensified control measures are required to prevent local transmission of leishmaniasis in Zhengzhou City.

Root Bark of Morus alba L. and Its Bioactive Ingredient, Ursolic Acid, Suppress the Proliferation of Multiple Myeloma Cells by Inhibiting Wnt/ß-Catenin Pathway.

The root bark of Morus alba L. has cytotoxic activity against several types of cancer cells. However, little is known about its chemopreventive mechanisms and bioactive metabolites. In this study, we showed that M. alba L. root bark extracts (MRBE) suppressed ß-catenin response transcription (CRT), which is aberrantly activated in various cancers, by promoting the degradation of ß-catenin. In addition, MRBE repressed the expression of the ß-catenin/T-cell factor (TCF)-dependent genes, cmyc and cyclin D1, thus inhibiting the proliferation of RPMI-8226 multiple myeloma (MM) cells. MRBE induced apoptosis in MM cells, as evidenced by the increase in the population of annexin VFITC- positive cells and caspase-3/7 activity. We identified ursolic acid in MRBE through LC/mass spectrum (MS) and observed that it also decreased intracellular ß-catenin, c-myc, and cyclin D1 levels. Furthermore, it suppressed the proliferation of RPMI-8226 cells by stimulating cell cycle arrest and apoptosis. These findings suggest that MRBE and its active ingredient, ursolic acid, exert antiproliferative activity by promoting the degradation of ß-catenin and may have significant chemopreventive potential against MM.

Ginsenoside Rg4 Enhances the Inductive Effects of Human Dermal Papilla Spheres on Hair Growth Via the AKT/GSK-3ß/ß-Catenin Signaling Pathway.

Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities including antioxidant and anti-inflammatory properties in several cell types. The purpose of this study was to use an in vivo model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 µg/ml) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Rg4 also increased the mRNA and protein expression of DP signature genes that are related to hair growth including ALP, BMP2, and VCAN in the DP spheres. Analysis of the signaling molecules and luciferase reporter assays further revealed that Rg4 induces the activation of phosphoinositide 3-kinase (PI3K)/AKT and the inhibitory phosphorylation of GSK3ß, which activates the WNT/ß-catenin signaling pathway. These results correlated with not only the increased nuclear translocation of ß-catenin following the treatment of the DP spheres with Rg4 but also the significant elevation of mRNA expression of the downstream target genes of the WNT/ß-catenin pathway including WNT5A, ß-catenin, and LEF1. In conclusion, these results demonstrated that ginsenoside Rg4 promotes the hair-inductive properties of DP cells by activating the AKT/GSK3ß/ß-catenin signaling pathway in DP spheres, suggesting that Rg4 could be a potential natural therapy for hair growth.

Role of Hypoxia Inducible Factor-1α in Alzheimer's Disease.

Amyloid-ß (Aß) peptides and hyperphosphorylated tau protein are the most important pathological markers of Alzheimer's disease (AD). Neuroinflammation and oxidative stress are also involved in the development and pathological mechanism of AD. Hypoxia inducible factor-1α (HIF-1α) is a transcriptional factor responsible for cellular and tissue adaption to low oxygen tension. Emerging evidence has revealed HIF-1α as a potential medicinal target for neurodegenerative diseases. On the one hand, HIF-1α increases AßPP processing and Aß generation by promoting ß/γ-secretases and suppressing α-secretases, inactivates microglia and reduces their activity, contributes to microglia death and neuroinflammation, which promotes AD pathogenesis. On the other hand, HIF-1α could resist the toxic effect of Aß, inhibits tau hyperphosphorylation and promotes microglial activation. In summary, this review focuses on the potential complex roles and the future perspectives of HIF-1α in AD, in order to provide references for seeking new drug targets and treatment methods for AD.

Genome-Wide Characterization and Expression Analysis of the HD-ZIP Gene Family in Response to Salt Stress in Pepper.

HD-ZIP is a unique type of transcription factor in plants, which are closely linked to the regulation of plant growth and development, the response to abiotic stress, and disease resistance. However, there is little known about the HD-ZIP gene family of pepper. In this study, 40 HD-ZIP family members were analyzed in the pepper genome. The analysis indicated that the introns number of Ca-HD-ZIP varied from 1 to 17; the number of amino acids was between 119 and 841; the theoretical isoelectric point was between 4.54 and 9.85; the molecular weight was between 14.04 and 92.56; most of them were unstable proteins. The phylogenetic tree divided CaHD-ZIP into 4 subfamilies; 40 CaHD-ZIP genes were located on different chromosomes, and all of them contained the motif 1; two pairs of CaHD-ZIP parallel genes of six paralogism genes were fragment duplications which occurred in 58.28~88.24 million years ago. There were multiple pressure-related action elements upstream of the start codon of the HD-Z-IP family. Protein interaction network proved to be coexpression phenomenon between ATML1 (CaH-DZ22, CaHDZ32) and At4g048909 (CaHDZ12, CaHDZ31), and three regions of them were highly homology. The expression level of CaHD-ZIP gene was different with tissues and developmental stages, which suggested that CaHD-ZIP may be involved in biological functions during pepper progress. In addition, Pepper HD-ZIP I and II genes played a major role in salt stress. CaHDZ03, CaHDZ 10, CaHDZ17, CaHDZ25, CaHDZ34, and CaHDZ35 were significantly induced in response to salt stress. Notably, the expression of CaHDZ07, CaHDZ17, CaHDZ26, and CaHDZ30, homologs of Arabidopsis AtHB12 and AtHB7 genes, was significantly upregulated by salt stresses. CaHDZ03 possesses two closely linked ABA action elements, and its expression level increased significantly at 4 h under salt stress. qRT-P-CR and transcription analysis showed that the expression of CaHDZ03 and CaHDZ10 was upregulated under short-term salt stress, but CaHDZ10 was downregulated with long-term salt stress, which provided a theoretical basis for research the function of Ca-HDZIP in response to abiotic stress.