OBJECTIVES

In Asia, younger individuals (below age 45) are diagnosed to have type 2 diabetes with increased rates of obesity defined by lower BMI yet with greater visceral adiposity (waist circumference and waisthip ratios). The prevalence data on type 1 diabetes is not well established, considered to be low, but is seen to be increasing as well. This changing phenotype therefore, presents a clinical dilemma in terms of correctly classifying diabetes and deciding on the consequent appropriate treatment. Distinguishing type 1 from type 2 diabetes has become more difficult with type 2 diabetes dramatically increasing in young adults and children. This study aims to define the characteristics of diabetes among young adults in the Philippines to provide a basis for appropriate management amidst changes in diabetes phenotypes seen globally.

METHODS

In this cross-sectional analytic study, we characterized the demographic, metabolic, and autoimmune features of diabetes among young adult Filipinos aged 18 to 45 years old consulting at a tertiary referral center in Manila, Philippines. Baseline serum A1c, FBS, 75-g oral glucose tolerance test, insulin, serum C-peptide, insulin autoantibodies, leptin, adiponectin, lipid profile, and thyroid function tests were obtained from the participants and analyzed. The homeostasis model assessment (HOMA) was used to estimate the insulin sensitivity.

RESULTS

A total of 348 patients with diabetes were included, with females comprising two-thirds of the participants. The mean age at diagnosis of diabetes was 35.9±7.22 years. The mean BMI was 28.12 kg/m2, with median waist to hip ratio (WHR) of 0·93. Metabolic syndrome was found in 60% of participants and 67.82% were obese by body mass index. The mean A1c was 9.07±2.52%. Good glucose control (A1c less than 7.0%) was seen in 23% of participants  while nearly half (48%) had HbA1c which was >9.0%. The median levels of fasting insulin and C-peptide were 12.62 (range 1.33–90.42) mIU/L and 0.78 ng/mL (range 0–16.2), respectively. 

Included participants were diagnosed with diabetes within a year and as such, majority did not have any micro- or macrovascular complications. The most common diabetes complication was sensory neuropathy detected by monofilament testing, which was found in 28% of participants, followed by non-proliferative diabetic retinopathy in 13%. A history of previous diabetic ketoacidosis was found in 10 patients (2.87%). Glutamic acid decarboxylase (GAD) and insulin auto-antibodies were found in 3.2% and 19.3% of participants, respectively. Approximately half (51.73%) of the participants were insulin resistant by HOMA-IR.

CONCLUSION

In contrast with Caucasians and other Asians, diabetes among young Filipino adults is associated with lower BMI but with a similarly high visceral adiposity as shown by an elevated WHR. Metabolic syndrome with insulin resistance as defined by a variety of indices is predominant. Type 1 diabetes with autoantibodies occur in only a small fraction of this population. Data derived from this work can provide a framework for cluster analysis towards personalized management specific to this population.

Human ; Acids ; Adiponectin ; Adiposity ; Adult ; Aged ; Antibodies ; Asia ; Asian ; Asian Continental Ancestry Group ; Autoantibodies ; Body Mass Index ; C-peptide ; Carboxy-lyases ; Child ; Cluster Analysis ; Demography ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis ; Diabetic Retinopathy ; Diagnosis ; Fasting ; Female ; Glucose ; Glucose Tolerance Test ; Glutamate Decarboxylase ; Glutamic Acid ; Insulin ; Insulin Resistance ; Ketosis ; Leptin ; Lipids ; Metabolic Syndrome ; Obesity ; Patients ; Peptides ; Phenotype ; Philippines ; Population ; Prevalence ; Serum ; Therapeutics ; Thyroid Gland ; Thyroid Function Tests ; Young Adult

OBJECTIVE: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling. METHODS: Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age- and sex-matched healthy controls. Univariate and multivariate analyses were simultaneously performed to identify the differential lipids. Multiple testing was controlled for using a false discovery rate (FDR) approach. Enrichment analysis was performed using MetaboAnalyst software. RESULTS: Based on the 294 lipids assayed, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used to distinguish patients with IS from healthy controls. Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection (VIP) greater than 1.0. These lipids were significantly enriched in glycerophospholipid metabolism (FDR-adjusted P = 0.009, impact score = 0.216). CONCLUSIONS Serum lipid profiles differed significantly between patients with IS and healthy controls. Thus, glycerophospholipid metabolism may be involved in the development of IS. These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
Humans ; Pilot Projects ; Lipidomics ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; Ischemic Stroke/blood* ; Aged ; China ; Lipids/blood* ; Adult ; Case-Control Studies ; East Asian People

With the continuous development of messenger RNA (mRNA) technology, mRNA-based drugs have shown broad application prospects in recent years. Since mRNA is easy to be degraded and difficult to enter cells directly, the mRNA delivery vectors have always been one of the focuses in the development of mRNA-based drugs. Although lipid nanoparticles (LNPs) have been widely used for the delivery of mRNA, they tend to accumulate in the liver, and repeated administration can easily induce inflammatory response which leads to tissue damage. Compared with LNPs, virus-like particles (VLPs) have the advantages of high biocompatibility and safety, being expected to offer new solutions for mRNA delivery. Based on the practical application requirements, this review summarized the research progress in VLPs according to the mRNA delivery steps: particle assembly, delivery into cells, and intracellular release. We hope to provide a basis and design ideas for the development of new VLPs as delivery vectors, promote the application of VLPs in mRNA delivery, and provide new possibilities for the research and application of mRNA-based therapeutics.
RNA, Messenger/administration & dosage* ; Humans ; Nanoparticles/chemistry* ; Genetic Vectors ; Lipids/chemistry* ; Drug Delivery Systems/methods* ; Virion ; Animals ; Gene Transfer Techniques ; Liposomes

Perilla frutescens (L.) Britt. is a characteristic oil crop rich in polyunsaturated fatty acids, particularly α-linolenic acid, which has important development and utilization value. The Dof transcription factor is one of the plant-specific transcription factor families, which is widely involved in important biological processes such as plant growth, development, and metabolic regulation. In order to explore the key Dof transcription factors involved in the oil biosynthesis and systematically analyze their regulatory mechanisms of P. frutescens seeds, a total of 56 PfDof gene family members were identified from the genome and transcriptome data of P. frutescens and classified into four subfamilies according to sequence characteristics. All PfDofs contained highly conserved C₂-C₂ zinc finger domains, with gene duplication being the primary mechanism driving their evolution and expansion. Genes within the same subgroup exhibited similar gene structures and conserved motifs. The 56 PfDofs were predicted as unstable hydrophilic proteins, with α-helixes and random coils as their predominant structural components. The RNA-seq results revealed that 11 PfDofs exhibited differential expression during different developmental stages of P. frutescens seeds. RT-qPCR was performed to further validate the expression patterns of these 11 members across various tissue samples (root, stem, leaf, and flower) of P. frutescens and at different developmental stages of its seeds. The results showed that PfDof29 exhibited the highest expression level in seeds, which was consistent with the transcriptome data. Subcellular localization studies demonstrated that PfDof29 was localized to the nucleus and had a transcriptional activation activity. Overexpression of PfDof29 in Nicotiana tabacum resulted in a significant increase in total oil content of tobacco leaves, accompanied by reductions in starch and soluble sugar content, while the protein content remained unchanged. Additionally, the metabolic balance between saturated and unsaturated fatty acids in the transgenic tobacco leaves was altered, with a significant increase in α-linolenic acid content. The expression levels of the fatty acid desaturase genes NtFAD2, NtFAD3, and NtFAD8 were significantly upregulated. A yeast one-hybrid assay revealed that PfDof29 could directly bind to the promoter region of PfFAD8, thereby regulating its expression. This study provides an initial understanding of the regulatory mechanisms of PfDof transcription factors in the synthesis and accumulation of oil in P. frutescens. These findings offer new insights into the enhancement of oil content and quality of P. frutescens seeds.
Transcription Factors/physiology* ; Perilla frutescens/metabolism* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; alpha-Linolenic Acid/biosynthesis* ; Lipids/biosynthesis* ; Seeds/genetics*

OBJECTIVE: To investigate the clinical value of MRI modified water-lipid separation technique (mDIXON-Quant) in terms of T2* values and fat fraction (FF) values for evaluating the degree of cervical intervertebral disc degeneration. METHODS: A total of 118 patients who underwent routine MRI of the cervical vertebra and the mDIXON-Quant examination in Fuyang People's Hospital from March 2019 to January 2024 were collected. The T2* values of C2/3 to C6/7 intervertebral discs and FF values of the upper and lower vertebral bodies were measured. Cervical intervertebral disc degeneration was graded according to the Pfirrmann criteria. The T2* values and FF values of different patients were compared with the Pfirrmann grades, and the correlation between T2* values, FF values, and Pfirrmann grades was analyzed by Spearman correlation. RESULTS: The T2* values of cervical intervertebral discs in grades I, II, III, IV, and V all showed a decreasing trend ( P＜0.05). The decreasing order of FF values in the upper cervical vertebra was IV, V, III, II, and I ( F=93.28, P＜0.05), and the decreasing order of FF values in the lower cervical vertebra was IV, III, V, II, and I ( F=112.037, P＜0.05). Spearman correlation analysis showed that the T2* values of cervical intervertebral discs were negatively correlated with the Pfirrmann grades ( P＜0.05), and the FF values of the upper and lower vertebrae were positively correlated with the Pfirrmann grades ( P＜0.05). CONCLUSION The mDIXON-Quant technique can be used to quantify the T2* values and FF values of cervical intervertebral disc degeneration and plays an important role in accurate clinical diagnosis and evaluation of treatment effects.
Humans ; Intervertebral Disc Degeneration/diagnostic imaging* ; Cervical Vertebrae/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Adult ; Intervertebral Disc/diagnostic imaging* ; Lipids

OBJECTIVES: Intracranial aneurysm (IA) has an insidious onset, and once ruptured, it carries high rates of mortality and disability. Cardiometabolic factors may be associated with the formation and rupture of IA. This study aims to summarize the application of Mendelian randomization (MR) methods in research on cardiometabolic factors and IA, providing insights for further elucidation of IA etiology and pathogenesis. METHODS: Literature about MR-based IA studies published up to February 21, 2024, was retrieved from PubMed, Embase, Web of Science, CNKI, and Wanfang. Two researchers independently performed literature screening, data extraction, and quality assessment. A narrative synthesis approach was used to conduct a qualitative systematic review of the included studies. RESULTS: A total of 11 MR-based studies on IA published between 2017 to 2024 were included, of which 4 were rated as high quality. These studies investigated the associations between blood pressure, blood lipids, blood glucose, obesity-related indicators, and inflammatory cytokines with IA and its subtypes, though issues of duplication were noted. Four MR studies based on the same European population but using different instrumental variable selection criteria, as well as another MR study in a different European cohort, consistently identified blood pressure as a risk factor for IA and its subtypes. Findings for blood lipids, blood glucose, obesity-related indicators, and inflammatory cytokines were inconsistent across MR studies. CONCLUSIONS Blood pressure appears to increase the risk of IA and its subtypes. Associations between other cardiometabolic factors and IA/subtypes require further in-depth investigation. Given the inherent limitations of MR studies, causal inferences should be made cautiously in combination with other lines of evidence.
Humans ; Mendelian Randomization Analysis ; Intracranial Aneurysm/etiology* ; Risk Factors ; Blood Pressure ; Blood Glucose ; Obesity/complications* ; Cardiometabolic Risk Factors ; Lipids/blood*

OBJECTIVES: To explore the lipidomic characteristics of children with bronchial asthma (hereafter referred to as asthma) and identify potential biomarkers for asthma. METHODS: A total of 26 asthmatic children were prospectively enrolled as the asthma group, and 20 healthy children served as the healthy control group. The asthma group was further divided into atopic (n=13) and non-atopic (n=13) subgroups based on IgE levels. Serum lipid metabolites were analyzed using liquid chromatography-mass spectrometry, followed by statistical analysis and data visualization. RESULTS: A total of 1 435 lipids were detected in the 46 children, primarily glycerophospholipids (625/1 435, 43.55%). Significant differences were observed in serum lipid profiles between the asthma and control groups. Twelve significantly differential lipids were identified, with receiver operating characteristic curve analysis showing that phosphatidylserine (PS)(18:0/20:4) and ceramide (Cer)(c16:0) exhibited the highest diagnostic value for asthma. The relative abundances of PS(18:0/20:4) and PS(18:0/22:6) were higher in the atopic subgroup than in the non-atopic subgroup (P<0.05) and positively correlated with total IgE levels in asthmatic children (r=0.675 and 0.740, respectively; P<0.05). CONCLUSIONS Asthmatic children exhibit significant lipid metabolic disturbances, primarily characterized by abnormal glycerophospholipid metabolism. Among these, PS(18:0/20:4) and Cer(c16:0) demonstrate specific alterations and may serve as potential diagnostic biomarkers for asthma. Furthermore, the positive correlation between PS(18:0/20:4) and PS(18:0/22:6) levels and serum total IgE suggests their possible involvement in immune regulation in asthma.
Humans ; Asthma/metabolism* ; Male ; Child ; Female ; Prospective Studies ; Mass Spectrometry/methods* ; Lipids/blood* ; Chromatography, Liquid/methods* ; Child, Preschool ; Immunoglobulin E/blood* ; Biomarkers/blood* ; Adolescent ; Liquid Chromatography-Mass Spectrometry

OBJECTIVES: To identify potential plasma lipidomic biomarkers that distinguish non-metastatic medulloblastoma (nmMB) from metastatic medulloblastoma (mMB) in children. METHODS: In this prospective study, 17 children with mMB and 20 matched children with nmMB were enrolled. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid metabolites were evaluated for their associations and diagnostic performance. RESULTS: Orthogonal partial least squares discriminant analysis based on lipid profiles clearly separated nmMB from mMB, and 14 differential lipids were identified, including DG(18:2/20:4/0:0) and SM(d18:1/20:0). Receiver operating characteristic analysis showed nine metabolites with area under the curve greater than 0.7. Differential lipids were enriched in sphingolipid, glycerophospholipid, and arachidonic acid metabolism, suggesting an association with the metastatic phenotype. CONCLUSIONS Plasma lipidomics provides a new approach to identify mMB, and the identified lipid metabolites may support early diagnosis and treatment, prognostic assessment, and selection of therapeutic targets for metastatic medulloblastoma.
Humans ; Medulloblastoma/diagnosis* ; Lipidomics ; Child ; Male ; Female ; Child, Preschool ; Cerebellar Neoplasms/blood* ; Biomarkers, Tumor/blood* ; Neoplasm Metastasis ; Prospective Studies ; Adolescent ; Lipids/blood*

Messenger RNA (mRNA) therapeutics involve delivering in vitro transcribed mRNA into specific cells to produce target proteins for the treatment or prevention of diseases. However, the development of mRNA therapeutics relies largely on mRNA delivery systems. Lipid nanoparticles (LNPs) represent the most widely used mRNA carriers in clinical applications. Composed of ionizable lipids, zwitterionic phospholipids, cholesterol, and polyethylene glycol-lipids, LNPs can address critical challenges in mRNA drug development, such as poor in vivo stability and the difficulty in crossing biological barriers. Ultimately, LNPs enable safe, efficient, and targeted mRNA delivery to the liver, lung, spleen, and other organs. This review outlines the roles of the four lipid components in LNPs for mRNA delivery. It then introduces targeted mRNA delivery to various organs/tissues such as the liver, lung, spleen, pancreas, bone marrow, and placenta, using strategies such as antibody modification, lipid structure alteration, and specialized administration routes. Additionally, this review discusses the applications and challenges of LNP-based mRNA therapeutics in disease treatment, aiming to provide insights for the clinical translation of mRNA therapies and for further innovations in LNP delivery systems.
Humans ; RNA, Messenger/administration & dosage* ; Nanoparticles/chemistry* ; Lipids/chemistry* ; Drug Delivery Systems ; Animals ; Liposomes

OBJECTIVE: To compare the lipid metabolites in the seminal plasma of normal fertile men from those of the patients with oligoasthenoteratozoospermia (OAT), and perform a pathway enrichment analysis on the differentially expressed lipids. METHODS: According to strict inclusion and exclusion criteria, we recruited 30 males seeking medical attention in our Center of Reproductive Medicine and equally divided them into an OAT and a normal fertile control group. Employing the untargeted metabolomics approach, we screened the differential lipids in the seminal plasma of the OAT patients and subjected them to pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. RESULTS: In the OAT patients, the expressions of 22 lipids were significantly upregulated and those of 32 downregulated in the positive ion mode, and the expressions of 2 lipids upregulated and those of 12 downregulated in the negative ion mode. And 5 of the significantly downregulated lipids, namely anandamide(20:4,n-6), adrenic acid, cis-gondoic acid, (3'-sulfo)galbeta-cer(d18:1/24:1(15Z)) and palmitoylcarnitine, were associated with 4 branches and 8 sub-branches of the KEGG metabolic pathways, among which the differential lipid anandamide (20:4,n-6) was involved in the regeneration of the biological system in the KEGG sub-pathway and considered to be a significantly differentially enriched pathway. CONCLUSION Lipid metabolites in the seminal plasma of OAT patients are significantly different from those in normal fertile males, and the differential lipid anandamide (20:4,n-6) may be involved in the regulation of sperm function and play an important role in male fertility.
Humans ; Male ; Semen/metabolism* ; Adult ; Lipids/analysis* ; Case-Control Studies ; Asthenozoospermia/metabolism* ; Oligospermia/metabolism* ; Lipid Metabolism ; Mass Spectrometry