Lipotoxicity: The missing link between diabetes and periodontitis?

Lipotoxicity refers to the accumulation of lipids in tissues other than adipose tissue (body fat). It is one of the major pathophysiological mechanisms responsible for the progression of diabetes complications such as non-alcoholic fatty liver disease and diabetic nephropathy. Accumulating evidence indicates that lipotoxicity also contributes significantly to the toxic effects of diabetes on periodontitis. Therefore, we reviewed the current in vivo, in vitro, and clinical evidence of the detrimental effects of lipotoxicity on periodontitis, focusing on its molecular mechanisms, especially oxidative and endoplasmic reticulum stress, inflammation, ceramides, adipokines, and programmed cell death pathways. By elucidating potential therapeutic strategies targeting lipotoxicity and describing their associated mechanisms and clinical outcomes, including metformin, statins, liraglutide, adiponectin, and omega-3 PUFA, this review seeks to provide a more comprehensive and effective treatment framework against diabetes-associated periodontitis. Furthermore, the challenges and future research directions are proposed, aiming to contribute to a more profound understanding of the impact of lipotoxicity on periodontitis.

Computational markers of risky decision-making predict for relapse to alcohol.

BACKGROUND: Relapse remains the major challenge in treatment of alcohol use disorder (AUD). Aberrant decision-making has been found as important cognitive mechanism underlying relapse, but factors associated with relapse vulnerability are unclear. Here, we aim to identify potential computational markers of relapse vulnerability by investigating risky decision-making in individuals with AUD. METHODS: Forty-six healthy controls and fifty-two individuals with AUD were recruited for this study. The risk-taking propensity of these subjects was investigated using the balloon analog risk task (BART). After completion of clinical treatment, all individuals with AUD were followed up and divided into a non-relapse AUD group and a relapse AUD group according to their drinking status. RESULTS: The risk-taking propensity differed significantly among healthy controls, the non-relapse AUD group, and the relapse AUD group, and was negatively associated with the duration of abstinence in individuals with AUD. Logistic regression models showed that risk-taking propensity, as measured by the computational model, was a valid predictor of alcohol relapse, and higher risk-taking propensity was associated with greater risk of relapse to drink. CONCLUSION: Our study presents new insights into risk-taking measurement and identifies computational markers that provide prospective information for relapse to drink in individuals with AUD.

Manipulating the Piezoelectric Response of Amino Acid-Based Assemblies by Supramolecular Engineering.

Variation in the molecular architecture significantly affects the electronic and supramolecular structure of biomolecular assemblies, leading to dramatically altered piezoelectric response. However, relationship between molecular building block chemistry, crystal packing and quantitative electromechanical response is still not fully understood. Herein, we systematically explored the possibility to amplify the piezoelectricity of amino acid-based assemblies by supramolecular engineering. We show that a simple change of side-chain in acetylated amino acids leads to increased polarization of the supramolecular arrangements, resulting in significant enhancement of their piezoelectric response. Moreover, compared to most of the natural amino acid assemblies, chemical modification of acetylation increased the maximum piezoelectric tensors. The predicted maximal piezoelectric strain tensor and voltage constant of acetylated tryptophan (L-AcW) assemblies reach 47 pm V-1 and 1719 mV m/N, respectively, comparable to commonly used inorganic materials such as bismuth triborate crystals. We further fabricated an L-AcW crystal-based piezoelectric power nanogenerator that produces a high and stable open-circuit voltage of over 1.4 V under mechanical pressure. For the first time, the illumination of a light-emitting diode (LED) is demonstrated by the power output of an amino acid-based piezoelectric nanogenerator. This work presents the supramolecular engineering toward the systematic modulation of piezoelectric response in amino acid-based assemblies, facilitating the development of high-performance functional biomaterials from simple, readily available, and easily tailored building blocks.

Self-Assembling Peptide-Based Functional Biomaterials.

Peptides can self-assemble into various hierarchical nanostructures through noncovalent interactions and form functional materials exhibiting excellent chemical and physical properties, which have broad applications in bio-/nanotechnology. The self-assembly mechanism, self-assembly morphology of peptide supramolecular architecture and their various applications, have been widely explored which have the merit of biocompatibility, easy preparation, and controllable functionality. Herein, we introduce the latest research progress of self-assembling peptide-based nanomaterials and review their applications in biomedicine and optoelectronics, including tissue engineering, anticancer therapy, biomimetic catalysis, energy harvesting. We believe that this review will inspire the rational design and development of novel peptide-based functional bio-inspired materials in the future.

Intramedullary spinal cord abscess with brain abscess due to subacute infective endocarditis.

BACKGROUND: Intramedullary spinal cord abscesses (ISCA) are rare, even more so in association with brain abscesses. Infective endocarditis is an uncommon cause of ISCA. In this case study, we report a patient with intramedullary abscesses and multiple brain abscesses due to subacute infective endocarditis. CASE PRESENTATION: A 54-year-old man presented with a 7-day history of head and neck pain and numbness in both lower limbs. Intramedullary abscess combined with multiple brain abscesses was diagnosed based on blood culture, head and spinal magnetic resonance imaging (MRI), contrast-enhanced MRI, and magnetic resonance spectroscopy. Echocardiography revealed vegetations on the mitral valve and severe mitral regurgitation, which the authors believe was caused by subacute infective endocarditis. With ceftriaxone combined with linezolid anti-infective therapy, the patient's symptoms and imaging was improved during follow-up. CONCLUSIONS: This case hopes to raise the vigilance of clinicians for ISCA. When considering a patient with an ISCA, it is necessary to complete blood culture, MRI of the brain and spinal cord, and echocardiography to further identify whether the patient also has a brain abscess and whether the cause is infective endocarditis.

Validation of a physiological type 2 diabetes model in human periodontal ligament stem cells.

OBJECTIVES: Type 2 diabetes (T2DM), a recognized risk factor for periodontitis, is characterized by insulin resistance. However, the molecular mechanisms concerning the role of insulin resistance in linking T2DM and periodontitis remain poorly elucidated due to the absence of an appropriate T2DM cell model. We aimed to explore an appropriate model of T2DM in human periodontal ligament stem cells (hPDLSCs) and uncover the involved mechanisms. MATERIALS AND METHODS: hPDLSCs were incubated with common reagents for recapitulating insulin resistance state including high glucose (HG) (15, 25, 35, 45 mM), glucosamine (0.8, 8, 18, 28, 38 mM), or palmitic acid (PA; 100, 200, 400, 800 µM), combined with LPS for 48 h. The insulin signaling pathway, inflammation, and pyroptosis were detected by western blots and quantitative real-time polymerase chain reaction (RT-qPCR). The effects on osteogenesis were evaluated by alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blots. RESULTS: HG failed to recapitulate insulin resistance. Glucosamine was sufficient to induce insulin resistance but failed to trigger inflammation. In total, 100 and 200 µM PA exhibited the most proinflammatory, insulin resistance, and pyroptosis induced role, and inhibited the osteogenic differentiation of hPDLSCs. CONCLUSION: Palmitic acid is a promising candidate for developing T2DM model in hPDLSCs.

Modulating the Electromechanical Response of Bio-Inspired Amino Acid-Based Architectures through Supramolecular Co-Assembly.

Supramolecular packing dictates the physical properties of bio-inspired molecular assemblies in the solid state. Yet, modulating the stacking modes of bio-inspired supramolecular assemblies remains a challenge and the structure-property relationship is still not fully understood, which hampers the rational design of molecular structures to fabricate materials with desired properties. Herein, we present a co-assembly strategy to modulate the supramolecular packing of N-terminally capped alanine-based assemblies (Ac-Ala) by changing the amino acid chirality and mixing with a nonchiral bipyridine derivative (BPA). The co-assembly induced distinct solid-state stacking modes determined by X-ray crystallography, resulting in significantly enhanced electromechanical properties of the assembly architectures. The highest rigidity was observed after the co-assembly of racemic Ac-Ala with a bipyridine coformer (BPA/Ac-DL-Ala), which exhibited a measured Young's modulus of 38.8 GPa. Notably, BPA crystallizes in a centrosymmetric space group, a condition that is broken when co-crystallized with Ac-L-Ala and Ac-D-Ala to induce a piezoelectric response. Enantiopure co-assemblies of BPA/Ac-D-Ala and BPA/Ac-L-Ala showed density functional theory-predicted piezoelectric responses that are remarkably higher than the other assemblies due to the increased polarization of their supramolecular packing. This is the first report of a centrosymmetric-crystallizing coformer which increases the single-crystal piezoelectric response of an electrically active bio-inspired molecular assembly. The design rules that emerge from this investigation of chemically complex co-assemblies can facilitate the molecular design of high-performance functional materials comprised of bio-inspired building blocks.

Smart MOF-on-MOF Hydrogel as a Simple Rod-shaped Core for Visual Detection and Effective Removal of Pesticides.

The immoderate use of pesticides in the modern agricultural industry has led to the pollution of water resources and ultimately threatens the human body. Herein, two metal-organic frameworks (MOFs), namely {[Zn(tpt)2 ·2H2 O]}n (Zn1) and {[Zn2 (tpt)2 (bdc)]}n (Zn2), (Htpt = 5-[4(1H-1,2,4-triazol-1-yl)]phenyl-2H-tetrazole), respectively, are constructed as smart materials for visual and on-site detection of pesticides and their removal from water. The exposed nitrogen-rich sites and high chemical stability make Zn2 a self-assembly core to further fabricate MOF-on-MOF-sodium alginate (ZIF-8-on-Zn2@SA) composite by wrapping ZIF-8 on the outside surface. Inheriting the excellent fluorescent emission of Zn2, the rod-like ZIF-8-on-Zn2@SA module exhibits naked-eye detection of thiophanate-methyl (TM) in real fruits and vegetables with a broad linear range (10-100 × 10-6  m), a low limit of detection (LOD = 0.14 × 10-6  m), and satisfactory recoveries (98.30-102.70%). In addition, carbendazim (CBZ), the metabolite of TM after usage in crops, can be efficiently removed from water by the ZIF-8-on-Zn2@SA (qmax  = 161.8 mg g-1 ) with a high correlation coefficient (R2  > 0.99). Therefore, the portable ZIF-8-on-Zn2@SA sensing platform presents a promising candidate for monitoring and removal of pesticides, especially suitable for regions with serious pesticide environmental pollution.

Prognostic Value of Pretreatment Skeletal Muscle Mass Index in Esophageal Cancer Patients: A Meta-Analysis.

The prognostic role of pretreatment skeletal muscle mass index (SMI) has been verified in several types of cancers. However, it remains unclear whether pretreatment SMI is a valuable prognostic indicator in esophageal cancer. The aim of the present study was to identify the prognostic value of pretreatment SMI in esophageal cancer. PubMed, EMBASE and Web of Science databases were searched for relevant studies up to November 10, 2021. The hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the association of pretreatment SMI with the overall survival (OS) and disease-free survival (DFS) of esophageal cancer patients. In total, 17 studies involving 2441 patients were included in this meta-analysis. The pooled results demonstrated that a lower SMI was significantly associated with poorer OS (HR = 1.18, 95% CI: 1.09-1.27, P < 0.001) and DFS (HR = 1.78, 95% CI: 1.10-2.88, P = 0.019). In addition, subgroup analysis based on treatment (surgery vs. nonsurgery), tumor type (squamous cell carcinoma vs. adenocarcinoma) and cutoff value of SMI showed similar results. The present findings demonstrated that pretreatment SMI is an independent prognostic indicator for esophageal cancer patients, and patients with a lower pretreatment SMI are more likely to have a worse prognosis. However, additional prospective high-quality studies are needed to verify the above findings.

Brain alterations in sensorimotor and emotional regions associated with temporomandibular disorders.

OBJECTIVES: Temporomandibular disorders (TMD) are characterized by sensorimotor and psychological dysfunction, with evidence revealing the implication of a dysfunctional central nervous system. Previous magnetic resonance imaging (MRI) studies have reported brain alterations in TMD, but most studies focused on either structure or function by a single modality of MRI and investigated static functional connectivity (FC) in TMD. By combining structural and functional MRI data, the present study aimed to identify brain regions with structural abnormalities in TMD patients and examine static and dynamic FC seeded by these regions to investigate structural brain alterations and related disrupted FC underlying the pathophysiology of TMD. METHODS: We recruited 30 TMD patients and 20 healthy controls who underwent 3.0 T MRI scanning with T1-weighted images using a three-dimensional magnetization-prepared rapid gradient-echo sequence and resting state functional images using a gradient-echo echo-planar imaging sequence. Cortical thickness, volume, surface area, and subcortical volume were calculated, where brain areas with significant structural between-group differences were treated as seeds for static and dynamic FC analyses. RESULTS: In this preliminary study, we found between-group alterations in sensorimotor regions including decreased cortical thickness in the right sensorimotor cortex as well as decreased volume in the left putamen and associated reduced dynamic FC with the anterior midcingulate cortex; and alterations in emotion processing and regulation regions including decreased volume/surface area in the left posterior superior temporal gyrus and associated increased dynamic FC with the precuneus in TMD patients than controls, having all p < 0.05 with corrections for multiple comparisons. CONCLUSION: Our findings of structural and functional abnormalities in brain regions implicated in sensorimotor and emotional functions provided evidence for the biopsychosocial model of TMD and facilitated our understanding of the pathophysiological mechanism underlying TMD. The associations between neuroimaging results and clinical measurements of TMD warrant further exploration.

A single point mutation in the hyaC gene affects Pasteurella multocida serovar A capsule production and virulence.

Pasteurella multocida (P. multocida) is a Gram-negative bacterium which causes diseases in poultry, livestock, and humans, resulting in huge economic losses. P. multocida serovar A CQ6 (PmCQ6) is a naturally occurring attenuated strain with a thin capsule. Thus, we aimed to explore why this strain is less virulent and produces less capsule compared with P. multocida serovar A strain CQ2 (PmCQ2). Analysis of capsular polysaccharide synthesis genes in PmCQ6 revealed that, compared with PmCQ2, there was only a single point mutation in the initiation codon sequence of the hyaC gene. To test whether this point mutation caused capsular deficiency and reduced virulence, we rescued this hyaC mutation and observed a restoration of capsule production and higher virulence. Transcriptome analysis showed that the hyaC point mutation led to a downregulation of capsule synthesis and/or iron utilization related-genes. Taken together, the results indicate that the start codon mutation of hyaC is an important factor affecting the capsule synthesis and virulence of PmCQ6.

Rifampicin impairs adipogenesis by suppressing NRF2-ARE activity in mice fed a high-fat diet.

Prolonged treatment with rifampicin (RFP), a first-line antibacterial agent used in the treatment of drug-sensitive tuberculosis, may cause various side effects, including metabolic disorders. The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2, also known as NRF2) plays an essential regulatory role in cellular adaptive responses to stresses via the antioxidant response element (ARE). Our previous studies discovered that NRF2 regulates the expression of CCAAT-enhancer-binding protein ß (Cebpb) and peroxisome proliferator-activated receptor gamma (Pparg) in the process of adipogenesis. Here, we found that prolonged RFP treatment in adult male mice fed a high-fat diet developed insulin resistance, but reduced fat accumulation and decreased expression of multiple adipogenic genes in white adipose tissues. In 3 T3-L1 preadipocytes, RFP reduced the induction of Cebpb, Pparg and Cebpa at mRNA and protein levels in the early and/or later stage of hormonal cocktail-induced adipogenesis. Mechanistic investigations demonstrated that RFP inhibits NRF2-ARE luciferase reporter activity and expression of NRF2 downstream genes under normal culture condition and in the early stage of adipogenesis in 3 T3-L1 preadipocytes, suggesting that RFP can disturb adipogenic differentiation via NRF2-ARE interference. Taken together, we demonstrate a potential mechanism that RFP impairs adipose function by which RFP likely inhibits NRF2-ARE pathway and thereby interrupts its downstream adipogenic transcription network.

Long non-coding RNAs: Emerging roles in periodontitis.

Periodontitis is a major burden of public health, affecting 20%-50% of the global population. It is a complex inflammatory disease characterized by the destruction of supporting structures of the teeth, leading to tooth loss and the emergence or worsening of systematic diseases. Understanding the molecular mechanisms underlying the physiopathology of periodontitis is beneficial for targeted therapeutics. Long non-coding RNAs (lncRNAs), transcripts made up of more than 200 nucleotides, have emerged as novel regulators of many biological and pathological processes. Recently, an increasing number of dysregulated lncRNAs have been found to be implicated in periodontitis. In this review, an overview of lncRNAs, including their biogenesis, characteristics, function mechanisms and research approaches, is provided. And we summarize recent research reports on the emerging roles of lncRNAs in regulating proliferation, apoptosis, inflammatory responses, and osteogenesis of periodontal cells to elucidate lncRNAs related physiopathology of periodontitis. Furthermore, we have highlighted the underlying mechanisms of lncRNAs in periodontitis pathology by interacting with microRNAs. Finally, the potential clinical applications, current challenges, and prospects of lncRNAs as diagnostic and prognostic biomarkers and therapeutic targets for periodontitis disease are discussed.

Mutagenicity, health risk, and disease burden of exposure to organic micropollutants in water from a drinking water treatment plant in the Yangtze River Delta, China.

A wide variety of organic micropollutants in drinking water pose a serious threat to human health. This study was aimed to reveal the characteristics of organic micropollution profiles in water from a drinking water treatment plant (DWTP) in the Yangtze River Delta, China and investigate the mutagenicity, health risk and disease burden through mixed exposure to micropollutants in water. The presence of organic micropollutants in seven categories in organic extracts (OEs) of water from the DWTP was determined, and Ames test was conducted to test the mutagenic effect of OEs. Meanwhile, health risk of exposure to organic micropollutants in finished water through three exposure routes (ingestion, dermal absorption and inhalation) was assessed with the method proposed by U.S. EPA, and disability-adjusted life years (DALYs) were combined to estimate the disease burden of cancer based on the carcinogenic risk (CR) assessment. The results showed that 28 organic micropollutants were detected in the raw and finished water at total concentrations of 967.28 ng/L and 1073.45 ng/L, respectively, of which phthalate esters (PAEs) were the dominant category (95.79% in the raw water and 96.61% in the finished water). Although the results of the Ames test for OEs were negative and the non-carcinogenic hazard index of the organic micropollutants in the finished water was less than 1 in all age groups, the total CR was 2.17 × 10-5, higher than the negligible risk level (1.00 × 10-6). The total DALYs caused by the organic micropollutants in the finished water was 2945.59 person-years, and the average individual DALYs was 2.21 × 10-6 per person-year (ppy), which was 2.21 times the reference risk level (1.00 × 10-6 ppy) defined by the WHO. Exposure to nitrosamines (NAms) was the major contributor to the total CR (92.06%) and average individual DALYs (94.58%). This study demonstrated that despite the negative result of the mutagenicity test with TA98 and TA100 strains, the health risk of exposure to organic micropollutants in drinking water should not be neglected.

Notch signaling inhibition protects against root resorption in experimental immature tooth movement in rats.

INTRODUCTION: This study aimed to build an experimental immature tooth movement model and verify less resorption of incompletely developed roots than those fully developed during the same orthodontic treatment, followed by investigating the cellular and molecular mechanism. METHODS: The development of Wistar rat tooth was investigated using in vivo microcomputed tomography and hematoxylin and eosin staining to decide the optimal ages of rats for immature tooth and mature tooth groups. The rats in the immature tooth and mature tooth groups were divided into experimental, sham control, and blank control groups. After orthodontic treatment for 3 weeks, the mesial root volume, crown movement distance, neck movement distance, root inclination, and apical distance were measured by microcomputed tomography. The expressions of TRAP, Jagged1, Notch2, IL-6, and RANKL were analyzed by immunohistochemical staining and real-time polymerase chain reaction. The repair of root resorption was also investigated after removing orthodontic force for 3 and 6 weeks. RESULTS: The root achieved the development stage around 10 weeks, so 4-week-old rats and 10-week-old rats were used in the immature tooth group and mature tooth group, respectively. The volume of root resorption in the experimental immature tooth group was 0.0869 ± 0.0244 mm3, which was less than that in the mature tooth group (0.1218 ± 0.0123 mm3) (P <0.001). Immature tooth movement decreased TRAP-positive odontoclasts on the compression side while having no statistically significant effect on osteoclasts. The protein expression of Jagged1, Notch2, IL-6, and RANKL in the mature tooth group increased significantly compared with the immature tooth group, not only on the compression side but also on the tension sides. The mRNA expression of Jagged1, Notch2, and RANKL was significantly lower in the immature tooth group, whereas the expression of IL-6 had no significance but a strong tendency. The root volume after repairing for 3 weeks was still less than that of blank control, whereas after repairing for 6 weeks, the difference was not statistically significant. CONCLUSIONS: The experimental immature tooth movement model for the Wistar rat was achieved for the first time. The immature tooth will suffer less root resorption than the mature tooth, which may be due to odontoclastogenesis inhibition by decreased expression of Jagged1/Notch2/IL-6/RANKL signaling.

Association between root resorption and tooth development: A quantitative clinical study.

INTRODUCTION: The aim of this study was to verify less resorption of incompletely developed roots compared with those that were fully developed during the same orthodontic treatment and to test the value of the amount of external apical root resorption for predicting tooth development. METHODS: A sample of 524 patients aged 10-15 years was selected following the inclusion criteria. For each subject, pretreatment and posttreatment digital panoramic and lateral radiographs were collected, and tooth development was determined from each radiograph. Through calculations, the amount of root resorption was assessed by a created and scientific approach for large-scale application using radiographs with only 8 measurement indexes for each patient. Other basic information and treatment parameters regarded as possible risk factors were also collected from standardized recordings or radiographs. The root length between the groups or in the single group were compared with t tests and correlation analyses. Linear univariate and multivariate regression analyses were used to test identify predictors for root resorption and to develop a prediction model. RESULTS: There was a statistically significant difference in the amount of root resorption with tooth development before correction (P <0.001) as well as after correction (P = 0.002). There was a statistically significant correlation (P <0.001) but no difference between pretreatment and posttreatment root length in the immature tooth group because of less root resorption. In the multivariate analyses, tooth development (P <0.001), treatment duration, apex horizontal movements, apex vertical movements, and previous orthodontic treatment were included in the final model as risk factors, and tooth development had the highest beta value. CONCLUSIONS: There is an association between root resorption and tooth development, and tooth development is an important predictor of root resorption. Patients with immature teeth are at a much lower risk of apical root resorption.

The neuro-pathophysiology of temporomandibular disorders-related pain: a systematic review of structural and functional MRI studies.

Chronic pain surrounding the temporomandibular joints and masticatory muscles is often the primary chief complaint of patients with temporomandibular disorders (TMD) seeking treatment. Yet, the neuro-pathophysiological basis underlying it remains to be clarified. Neuroimaging techniques have provided a deeper understanding of what happens to brain structure and function in TMD patients with chronic pain. Therefore, we performed a systematic review of magnetic resonance imaging (MRI) studies investigating structural and functional brain alterations in TMD patients to further unravel the neurobiological underpinnings of TMD-related pain. Online databases (PubMed, EMBASE, and Web of Science) were searched up to August 3, 2019, as complemented by a hand search in reference lists. A total of 622 papers were initially identified after duplicates removed and 25 studies met inclusion criteria for this review. Notably, the variations of MRI techniques used and study design among included studies preclude a meta-analysis and we discussed the findings qualitatively according to the specific neural system or network the brain regions were involved in. Brain changes were found in pathways responsible for abnormal pain perception, including the classic trigemino-thalamo-cortical system and the lateral and medial pain systems. Dysfunction and maladaptive changes were also identified in the default mode network, the top-down antinociceptive periaqueductal gray-raphe magnus pathway, as well as the motor system. TMD patients displayed altered brain activations in response to both innocuous and painful stimuli compared with healthy controls. Additionally, evidence indicates that splint therapy can alleviate TMD-related symptoms by inducing functional brain changes. In summary, MRI research provides important novel insights into the altered neural manifestations underlying chronic pain in TMD.

l-Serine Lowers the Inflammatory Responses during Pasteurella multocida Infection.

Pasteurella multocida causes a variety of infectious diseases in various species of mammals and birds, resulting in enormous economic loss to the modern livestock and poultry industry. However, the mechanism of host-pathogen interaction is unclear. Here, we found that l-serine levels were significantly decreased in murine lungs infected with P. multocida Exogenous l-serine supplementation significantly increased the survival rate of mice and decreased the colonization of P. multocida in the lungs of mice. Notably, l-serine decreased the macrophage- and neutrophil-mediated inflammatory responses in mice during P. multocida infection.

Natural products as modulator of autophagy with potential clinical prospects.

Natural compounds derived from living organisms are well defined for their remarkable biological and pharmacological properties likely to be translated into clinical use. Therefore, delving into the mechanisms by which natural compounds protect against diverse diseases may be of great therapeutic benefits for medical practice. Autophagy, an intricate lysosome-dependent digestion process, with implications in a wide variety of pathophysiological settings, has attracted extensive attention over the past few decades. Hitherto, accumulating evidence has revealed that a large number of natural products are involved in autophagy modulation, either inducing or inhibiting autophagy, through multiple signaling pathways and transcriptional regulators. In this review, we summarize natural compounds regulating autophagy in multifarious diseases including cancer, neurodegenerative diseases, cardiovascular diseases, metabolic diseases, and immune diseases, hoping to inspire further investigation of the underlying mechanisms of natural compounds and to facilitate their clinical use for multiple human diseases.

Current situation and future usage of anticancer drug databases.

Cancer is a deadly disease with increasing incidence and mortality rates and affects the life quality of millions of people per year. The past 15 years have witnessed the rapid development of targeted therapy for cancer treatment, with numerous anticancer drugs, drug targets and related gene mutations been identified. The demand for better anticancer drugs and the advances in database technologies have propelled the development of databases related to anticancer drugs. These databases provide systematic collections of integrative information either directly on anticancer drugs or on a specific type of anticancer drugs with their own emphases on different aspects, such as drug-target interactions, the relationship between mutations in drug targets and drug resistance/sensitivity, drug-drug interactions, natural products with anticancer activity, anticancer peptides, synthetic lethality pairs and histone deacetylase inhibitors. We focus on a holistic view of the current situation and future usage of databases related to anticancer drugs and further discuss their strengths and weaknesses, in the hope of facilitating the discovery of new anticancer drugs with better clinical outcomes.