Prediction of blood-brain barrier penetrating peptides based on data augmentation with Augur.

BACKGROUND: The blood-brain barrier serves as a critical interface between the bloodstream and brain tissue, mainly composed of pericytes, neurons, endothelial cells, and tightly connected basal membranes. It plays a pivotal role in safeguarding brain from harmful substances, thus protecting the integrity of the nervous system and preserving overall brain homeostasis. However, this remarkable selective transmission also poses a formidable challenge in the realm of central nervous system diseases treatment, hindering the delivery of large-molecule drugs into the brain. In response to this challenge, many researchers have devoted themselves to developing drug delivery systems capable of breaching the blood-brain barrier. Among these, blood-brain barrier penetrating peptides have emerged as promising candidates. These peptides had the advantages of high biosafety, ease of synthesis, and exceptional penetration efficiency, making them an effective drug delivery solution. While previous studies have developed a few prediction models for blood-brain barrier penetrating peptides, their performance has often been hampered by issue of limited positive data. RESULTS: In this study, we present Augur, a novel prediction model using borderline-SMOTE-based data augmentation and machine learning. we extract highly interpretable physicochemical properties of blood-brain barrier penetrating peptides while solving the issues of small sample size and imbalance of positive and negative samples. Experimental results demonstrate the superior prediction performance of Augur with an AUC value of 0.932 on the training set and 0.931 on the independent test set. CONCLUSIONS: This newly developed Augur model demonstrates superior performance in predicting blood-brain barrier penetrating peptides, offering valuable insights for drug development targeting neurological disorders. This breakthrough may enhance the efficiency of peptide-based drug discovery and pave the way for innovative treatment strategies for central nervous system diseases.

Systematic review of fibroblastic rheumatism: A case report.

BACKGROUND: Fibroblastic rheumatism (FR) is a rare fibroproliferative disease with an unknown etiology. The absence of typical symptoms makes early diagnosis challenging. This study aims to systematically review FR cases and present a case from our center to provide a comprehensive description of the clinical manifestations, diagnosis, and treatment, thereby assisting clinicians in early identification and timely management of FR, ultimately leading to improved prognosis. CASE SUMMARY: FR is a rare fibroproliferative disease with an unknown etiology. It is characterized by rapidly progressive and destructive symmetrical inflammatory multiple arthritis. Here, we present a rare case of a 50-year-old female with symmetric inflammatory polyarthritis. We highlight the importance of a comprehensive medical history, histopathology, immunohistochemistry, and clinical manifestations of skin nodules, arthralgia, and arthritis for successful disease diagnosis. Despite employing non-steroidal anti-inflammatory drugs, corticosteroids, methotrexate, and tacrolimus, the patient's symptoms did not resolve, and joint destruction continued to progress. Early diagnosis, aggressive treatment with appropriate use of steroids and immunosuppressants, and further research to identify effective treatment strategies are crucial in preventing detrimental joint destruction and limb contractures. CONCLUSION: A comprehensive review of the available literature emphasizes the importance of early and accurate diagnosis coupled with appropriate treatment for achieving favorable outcomes and preventing joint destruction and limb contractures.

A study on the impact of the number of family generations on intergenerational support for centenarians: a study in a Chinese 'longevity city'.

BACKGROUND: As a natural source of support for the elderly, the family is an important channel for achieving a sense of security, happiness, and worthiness in old age. In this study, we analysed the characteristics of intergenerational support in families of centenarians and explored the impact of the number of family generations on intergenerational support. METHODS: We conducted a cross-sectional survey between April 2020 and January 2021 among 62 elderly people aged 99+ in Rugao, China, one of six 'longevity cities' in the world. Assisted by the researchers, centenarians completed questionnaires with details pertaining to general demographics, intergenerational support, and other aspects. We used a logistic regression model to analyse the influence of the number of family generations on intergenerational support that the centenarians received with respect to economic, living, and emotional aspects. RESULTS: Centenarians were primarily recipients of care in their families, and received intergenerational support mainly for their declined physical functions and limited self-care ability. The study results revealed that the greater the number of generations comprising the family, the greater was the intergenerational life care and emotional comfort provided for centenarians by the family. CONCLUSIONS: In this study, we found a positive effect of the number of family generations on intergenerational support for centenarians. The government and society should promote the tradition of respecting, caring for, and honouring the elderly while paying close attention to the dynamic changes in the family structure of centenarians in promoting high-quality and sustainable development of the people, economy, and society.

Bitter-RF: A random forest machine model for recognizing bitter peptides.

Introduction: Bitter peptides are short peptides with potential medical applications. The huge potential behind its bitter taste remains to be tapped. To better explore the value of bitter peptides in practice, we need a more effective classification method for identifying bitter peptides. Methods: In this study, we developed a Random forest (RF)-based model, called Bitter-RF, using sequence information of the bitter peptide. Bitter-RF covers more comprehensive and extensive information by integrating 10 features extracted from the bitter peptides and achieves better results than the latest generation model on independent validation set. Results: The proposed model can improve the accurate classification of bitter peptides (AUROC = 0.98 on independent set test) and enrich the practical application of RF method in protein classification tasks which has not been used to build a prediction model for bitter peptides. Discussion: We hope the Bitter-RF could provide more conveniences to scholars for bitter peptide research.

Puerarin extends the lifespan of Drosophila melanogaster by activating autophagy.

Lifespan longevity has attracted increasing attention with societal development. To counter the effects of aging on longevity, we focused on the natural chemicals of plants. In this study, we investigated the effects of puerarin supplementation on the lifespan of Drosophila melanogaster. Puerarin supplementation significantly extended the lifespan of D. melanogaster at 60 µM and 120 µM by upregulating proteasome subunit beta 5 (prosbeta5) and sirtuin-1 (Sirt1). However, puerarin-induced longevity of male flies (F0 generation) may not be passed on to descendants. Additionally, a puerarin diet for 10 and 25 days did not influence the body weight and food intake of male Canton-S flies. Puerarin significantly improved the climbing ability, starvation resistance, and oxidation resistance of male flies by upregulating the expression of Shaker, catalase (CAT), superoxide dismutase 1 (SOD1), and Methuselah, and downregulating poly [ADP-ribose] polymerase (PARP-1) and major heat shock 70 kDa protein Aa (HSP70). Moreover, 120 µM puerarin supplementation for 25 days significantly increased adenosine 5' triphosphate (ATP) content by increasing adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) levels. Additionally, the puerarin diet for 25 days suppressed male fecundity in male flies by decreasing the levels of Bam and Punt. Mechanistically, puerarin enhanced lysosome-involved autophagy by promoting the expression of lysosome markers [ß-galactosidase and lysosomal associated membrane protein 1 (LAMP1)], and elevating the levels of autophagy-related genes, including autophagy-associated gene 1 (ATG1), ATG5, and ATG8b. However, puerarin decreased the phosphorylation of the target of rapamycin (TOR) protein. In conclusion, puerarin is a promising compound for improving the longevity of D. melanogaster by activating autophagy.

Identification of adaptor proteins using the ANOVA feature selection technique.

The adaptor proteins play a crucially important role in regulating lymphocyte activation. Rapid and efficient identification of adaptor proteins is essential for understanding their functions. However, biochemical methods require not only expensive experimental costs, but also long experiment cycles and more personnel. Therefore, a computational method that could accurately identify adaptor proteins is urgently needed. To solve this issue, we developed a classifier that combined the support vector machine (SVM) with the composition of k-Spaced Amino Acid Pairs (CKSAAP) and the amino acid composition (AAC) to identify adaptor proteins. Analysis of variance (ANOVA) was used to select the optimized features which could generate the maximum prediction performance. By examining the proposed model on independent data, we found that the 447 optimized features could achieve an accuracy of 92.39% with an AUC of 0.9766, demonstrating the powerful capabilities of our model. We hope that the proposed model could provide more clues for studying adaptor proteins.

Single-Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring.

Centenarians, who show mild infections and low incidence of tumors, are the optimal model to investigate healthy aging. However, longevity related immune characteristics has not been fully revealed largely due to lack of appropriate controls. In this study, single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) derived from seven centenarians (CEN), six centenarians' offspring (CO), and nine offspring spouses or neighbors (Control, age-matched to CO) are performed to investigate the shared immune features between CEN and CO. The results indicate that among all 12 T cell clusters, the cytotoxic-phenotype-clusters (CPC) and the naïve-phenotype-clusters (NPC) significantly change between CEN and ontrol. Compared to Control, both CEN and CO are characterized by depleted NPC and increased CPC, which is dominated by CD8+ T cells. Furthermore, CPC from CEN and CO share enhanced signaling pathways and transcriptional factors associated with immune response, and possesse similar T-cell-receptor features, such as high clonal expansion. Interestingly, rather than a significant increase in GZMK+ CD8 cells during aging, centenarians show accumulation of GZMB+ and CMC1+ CD8 T cells. Collectively, this study unveils an immune remodeling pattern reflected by both quantitative increase and functional reinforcement of cytotoxic T cells which are essential for healthy aging.

The therapeutic role of mesenchymal stem cell-derived exosomes in the autoimmune diseases.

Autoimmune diseases are characterized by damage and dysfunction of multiple organs and various complications. Recently, new therapies for autoimmune diseases have been proposed extensively, and there are growing researches focusing on the immunomodulatory abilities of mesenchymal stem cells (MSCs). As a kind of small vesicles secreted by cells, exosomes can be released by MSCs and other cells. Being enriched with protein, mRNA, microRNA, lipids and other cell contents, exosomes participate in the transfer of substances and information between cells, and regulate the biological functions of recipient cells, which may be a potential mechanism of the immunomodulation abilities of MSCs. A growing number of studies have shown that the exosomes secreted by MSCs have similar or even better immunomodulation abilities than MSCs, and their roles in the treatment of several autoimmune diseases have been confirmed in animal models. In this review, we briefly summarize the effects of MSCs and the MSCs-derived exosomes on the immune system and immune cells, especially focusing on the research progress of MSCs-derived exosomes in autoimmune diseases in recent years.

BMI, Blood Pressure, and Plasma Lipids among Centenarians and Their Offspring.

BACKGROUND: The burden of cardiovascular diseases (CVDs) is increasing substantially due to population growth and aging. Determining effective prevention and understanding the underlying mechanisms remain desirable pursuits for increasing the quality of life. As centenarians and their offspring may have genetic advantages, they may present with healthier cardiovascular-related profiles. METHODS: We launched a cross-sectional household-based survey of centenarian families, including 253 centenarians, 217 centenarian offspring, and 116 offspring spouses without centenarian parents from county-level Chinese longevity city Rugao. Among offspring and offspring spouses were the following arrangements: 101 paired offspring and offspring spouses who lived together, 116 unpaired offspring, and 16 unpaired spouses. We investigated their cardiovascular-related health status including waist circumference, body mass index (BMI), blood pressure, and plasma lipids and compared results among centenarians, centenarian offspring, and offspring spouses. RESULTS: Centenarians ranged from 99 to 109 years with a median age of 100 years. Centenarian offspring, with a median age of 70 years, and offspring spouses, with a median age of 69 years, shared similar age. Results of blood pressure, plasma lipid levels, and BMI displayed no significant difference between centenarian offspring and offspring spouses. However, centenarians appeared to have lower waist circumference, BMI, TC, LDL-C, TG, and diastolic blood pressure but higher levels of systolic blood pressure (p < 0.05). Multivariate analysis showed the prevalence of obesity, hypertension, and dyslipidemia was similar between centenarian offspring and offspring spouses, while centenarians appeared to have a lower prevalence of obesity and a higher prevalence of hypertension (p < 0.05). CONCLUSIONS: Centenarians and centenarian offspring did not present healthier BMI, blood pressure, or plasma lipids than offspring spouses. Further research on longevity and cardiovascular diseases are desirable.

Higher dietary diversity as a protective factor against depression among older adults in China: a cross-sectional study.

BACKGROUND: Evidence suggests that poor mental health (MH) is a risk factor for the health of older adults. Dietary diversity is considered to be related to healthy aging. However, the relationship between diet and MH is still unclear. Therefore, the purpose of this study was to investigate the relationship between dietary diversity score (DDS) and anxiety and depression among centenarians and their offspring and spouses. METHODS: Our study was observational and cross-sectional. The Generalized Anxiety Disorder Scale (GAD-7), the 15-item version of the Geriatric Depression Scale (GDS-15), and the dietary frequency questionnaire were used to measure the status of anxiety, depression, and dietary diversity. Data were analyzed by Student's t-test, χ2 test, Mann-Whitney U test, correlational analysis, and univariate or multivariate logistic regression. RESULTS: Among the 288 older adults, 12.8% reported symptoms of depression, and 8.7% reported anxiety. People with a lower dietary diversity had higher rates of anxiety and depression. After controlling for age, place of residence, economic status, alcohol drinking, and physical activity, a lower DDS was found to be a risk factor for depressive symptoms [odds ratio (OR): 2.237; 95% confidence interval (CI): 1.009-4.959; P=0.048]. DDS was negatively correlated with depression score in older adults (r=-0.224; P<0.001), especially offspring and their spouses (r=-0.275; P<0.001). However, no significant relationship was observed between DDS and anxiety. In addition, eating legumes (OR: 0.415; 95% CI: 0.188-0.920; P=0.030) and nuts (OR: 0.255; 95% CI: 0.116-0.561; P=0.001) at least once a week can act as protective factors for depression. Eating nuts (OR: 0.405; 95% CI: 0.168-0.978; P=0.044) and meat (OR: 0.396, 95% CI: 0.161-0.975; P=0.044) at least once a week can act as protective factors for anxiety. CONCLUSIONS: These results suggest an association between low dietary diversity and a higher incidence of mental disorders. Further, the possibility of reverse causality cannot be ruled out. It is necessary to conduct further prospective studies.

Relevant Characteristics Analysis Using Natural Language Processing and Machine Learning Based on Phenotypes and T-Cell Subsets in Systemic Lupus Erythematosus Patients With Anxiety.

Anxiety is frequently observed in patients with systemic lupus erythematosus (SLE) and the immune system could act as a trigger for anxiety. To recognize abnormal T-cell and B-cell subsets for SLE patients with anxiety, in this study, patient disease phenotypes data from electronic lupus symptom records were extracted by using natural language processing. The Hospital Anxiety and Depression Scale (HADS) was used to distinguish patients, and 107 patients were selected to meet research requirements. Then, peripheral blood was collected from two patient groups for multicolor flow cytometry experiments. The characteristics of 75 T-cell and 15 B-cell subsets were investigated between SLE patients with- (n = 23) and without-anxiety (n = 84) groups by four machine learning methods. The findings showed 13 T-cell subsets were significantly different between the two groups. Furthermore, BMI, fatigue, depression, unstable emotions, CD27+CD28+ Th/Treg, CD27-CD28- Th/Treg, CD45RA-CD27- Th, and CD45RA+HLADR+ Th cells may be important characteristics between SLE patients with- and without-anxiety groups. The findings not only point out the difference of T-cell subsets in SLE patients with or without anxiety, but also imply that T cells might play the important role in patients with anxiety disorder.

[Exosomal microRNAs: an emerging player in systemic lupus erythematosus].

Exosomes are nanometer-sized membranous extracellular vesicles that can be secreted by almost all types of cells in the body. Exosomes are involved in cell-to-cell communication through autocrine and paracrine forms. Exosomal microRNAs (miRNAs) are stable in plasma, urine and other body fluids, and have various biological functions. They play an irreplaceable role in the occurrence, development, immune regulation of systemic lupus erythematosus (SLE). Recent studies have proposed that exosomal miRNAs have promising application prospects in the pathogenesis, early diagnosis, and treatment of SLE. Therefore, this review aims to introduce the current research progress on exosomal miRNAs in SLE and analyze their potential application value.

Inhibition of urease by extracts derived from 15 Chinese medicinal herbs.

CONTEXT: Helicobacter pylori is a major causative factor in gastritis-like disorders, and urease plays a key role in Helicobacter pylori colonizing and persisting in the mucous layer of the human stomach. In China, a variety of Chinese medicinal herbs have been prescribed to attenuate or eradicate gastritis-like disorders. However, little is known about the urease inhibition of Chinese medicinal herbs. OBJECTIVE: The present study was conducted to investigate the urease inhibition activities of the ethanol and water extracts of 15 Chinese medicinal herbs. MATERIALS AND METHODS: The ethanol and water extracts derived from 15 medicinal herbs, traditionally used for the treatment of gastritis-like disorders in China, were tested for urease-inhibition activity using the phenol red method. RESULTS: Screened at 10 µg/mL, 14 ethanol extracts and 10 water extracts showed urease inhibition. The ethanol extracts of Magnolia officinalis Rehd. et Wils. (Magnoliaceae) and Cassia obtusifolia L. (Leguminosae) possessed inhibition rates higher than 50% with IC50 values of 6.5 and 12.3 µg/mL, respectively. After fractionating successively, the petroleum ether fraction of the ethanol extracts of Magnolia officinalis showed the best activity with 90.8% urease inhibition at a concentration of 10 µg/mL. The bioautography of the petroleum ether fraction indicated the existence of the urease inhibitors in the herb. DISCUSSION AND CONCLUSION: The present results indicated that some Chinese medicinal herbs might treat gastritis-like disorders via the inhibition of Helicobacter pylori urease and the further possibility for discovering useful novel urease inhibitors from the Chinese medicinal herbs.

[The effect of umbilical cord mesenchymal stem cell transplantation on interstitial pneumonitis in MRL/lpr mice].

OBJECTIVE: To investigate the effects of umbilical cord mesenchymal stem cell (UC-MSCs) transplantation on interstitial pneumonitis in MRL/lpr mice. METHODS: Twenty four 18-week-old MRL/lpr female mice were randomly divided into 3 groups: the single dose group received a single dose of UC-MSCs (1 x 10(6)) transfusion intravenously, the 3 dose group received 3 injections of UC-MSCs (1 x 10(6)) weekly for 3 weeks, and the control mice were treated with saline. Both the control and the treated mice were sacrificed at 29 weeks. The histopathology of the lungs were assessed by HE staining. RESULTS: In comparison to the control mice, UC-MSCs transplantation significantly attenuated interstitial pneumonitis in the MRL/lpr mice. The peribronchiolar lesion indices of the single dose treatment group (1.40 +/- 0.24) and the 3 dose treatment group (1.02 +/- 0.29) were significantly decreased as compared to the control group (1.95 +/- 0.35), q = 0.551, 0.937, all P < 0.01. The perivascular lesion index of the single dose treatment group (1.20 +/- 0.18) and the 3 dose treatment group (1.08 +/- 0.16) were also significantly reduced as compared to the control group (1.56 +/- 0.32), q = 0.360, 0.479, P < 0.05, P < 0.01. The inflammatory cell infiltration index of the control group (1.72 +/- 0.34) was significantly increased compared to the single dose treatment group (1.30 +/- 0.21) and the 3 dose treatment group (1.05 +/- 0.15), q = 0.417, 0.673, P < 0.05, P < 0.01. CONCLUSIONS: These findings indicate that UC-MSCs have a pleiotropic therapeutic effect on pneumonitis in MRL/lpr mice.