Lipid droplets (LDs) are dynamic organelles that are ubiquitous across most organisms, including animals, plants, protists, and microorganisms. Their core consists of neutral lipids, surrounded by a phospholipid monolayer adorned with a specific set of proteins. As critical intracellular hubs of metabolic regulation, lipid droplets play essential roles in maintaining physiological homeostasis and contributing to the progression of various pathological processes. They store neutral lipids for energy production during periods of starvation or for membrane biosynthesis, and they sequester fatty acids to mitigate lipotoxicity. Clinically, dysregulation of lipid droplet function is associated with a wide range of diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD), obesity, type 2 diabetes mellitus (T2DM), neurodegenerative disorders, and cancer. Research into the biological functions of lipid droplets—as dynamic organelles and their links to multiple diseases—has emerged as a cutting-edge focus in cell biology. In recent years, significant advances have been made in understanding lipid droplet biogenesis. Researchers have developed a more refined framework that elucidates how LDs are assembled in the endoplasmic reticulum (ER). Triacylglycerols and sterol esters are synthesized between the inner and outer leaflets of the ER bilayer, and when they exceed the critical nucleation concentration (CNC), they coalesce to form neutral lipid lenses. These then bud from the ER under the coordinated action of key proteins such as Seipin, fat storage-inducing transmembrane protein 2 (FIT2), and the peroxisomal membrane protein Pex30. This budding process is driven by changes in membrane curvature and surface tension, induced by the asymmetric distribution of phospholipids. Nascent lipid droplets recruit lipid-synthesizing enzymes via ER-LD bridging structures, enabling localized lipid production and surface expansion, ultimately resulting in the formation of mature LDs. Biochemical and biophysical approaches have revealed important features of this process, underscoring the critical roles of ER membrane biophysical properties and specific phospholipids. Structural biology and proteomic studies have identified key regulators—particularly Seipin and FIT2—as central players in LD biogenesis. This review systematically summarizes recent advances in the molecular mechanisms of LD biogenesis. It delves into the processes of LD nucleation, membrane budding, and expansion in eukaryotic cells, with a special focus on how core factors such as Seipin and FIT2 dynamically regulate LD morphology. In addition, it examines the mechanisms and pathways by which class I and class II proteins are targeted to LDs, compares LD biogenesis involving different neutral lipid cores, and discusses the disease relevance of specific regulatory proteins. Finally, the review outlines critical unresolved questions in the field of LD biogenesis, offering clear directions for future research and providing a comprehensive framework for deepening our understanding of LD formation and its implications for disease intervention.

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with IgD multiple myeloma (MM). METHODS: The clinical data of 8 patients with IgD MM admitted to Gansu Provincial Hospital from September 2013 to February 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized. RESULTS: Among the 8 enrolled patients, there were 4 males and 4 females, with a median age of 60 (44-74) years. All patients had symptoms of renal insufficiency and anemia. There were 3 cases of bone invasion, 3 cases of splenomegaly, 7 cases of IgD-λ type, and 1 case of IgD-κ type. FISH examination was performed in 7 cases, and 6 of them were positive for 1q21 . There were 6 cases in DS stage III and 2 cases in DS stage II; According to ISS staging, there were 6 cases in stage III, 1 case in stage II, and 1 case in stage I; According to R-ISS staging, there were 5 cases in stage III and 3 cases in stage II. All patients received bortezomib-based combination chemotherapy, with 1 case undergoing autologous stem cell transplantation (ASCT) and 2 cases receiving daratumumab in combination. The median treatment period was 6 (1-15) cycles. The short-term efficacy was evaluated after 4-6 courses of treatment. Among the 6 patients with assessable efficacy, 1 case experienced disease progression (PD), and 5 cases achieved complete remission (CR). The median follow-up time was 26 (11-33) months, and the median progression-free survival (PFS) and median overall survival (OS) of the patients were 11.25 (3-26) months and 18.5 (4-33) months, respectively. Among the 8 patients, 4 cases died. Among the deceased patients, 3 cases were in R-ISS stage III and 3 cases were 1q21 positive. 2 of the 5 patients with early CR died due to disease progression. CONCLUSION The incidence of IgD MM is low, the symptoms of early renal damage, blood system damage and bone erosion in IgD MM patients are obvious, and the median survival time is short. ASCT and / or daratumumab may bring lasting relief for IgD MM patients, but large-scale clinical studies are still needed.
Humans ; Multiple Myeloma/therapy* ; Middle Aged ; Male ; Female ; Aged ; Prognosis ; Immunoglobulin D ; Adult ; Retrospective Studies

OBJECTIVE: To analyze the clinical characteristics and prognosis of patients with T-cell large granular lymphocytic leukemia (T-LGLL). METHODS: The clinical data of 7 patients with T-LGLL in Gansu Provincial Hospital from March 2016 to June 2023 were analyzed retrospectively. RESULTS: Among the 7 patients, 5 were male and 2 were female, with a median age of 51(28-83) years old. At the onset of illness, 6 cases showed symptoms of fatigue and anemia, 4 cases had enlarged lymph nodes, and 5 cases had splenomegaly. Examination showed that 4 cases were antinuclear antibody(ANA) positive, 5 cases were anemia. The median hemoglobin (Hb) level was 83(61-151) g/L, the median white blood cell count (WBC) was 5.6(2.0-8.7)×10⁹ /L, and the median percentage of lymphocytes in peripheral blood was 66.2(13.9-89.1)%. There were 3 cases with extremely active bone marrow hyperplasia, 2 cases with active hyperplasia, and 2 cases with decreased hyperplasia. There were 5 cases with mild myelofibrosis (MF-1), and 1 case with moderate myelofibrosis (MF-2). The median percentage of T cells was 64.3 (31.5-80.6)%. 5 cases showed the classic immunophenotype (CD3 ⁺ CD4^- CD8 ⁺), 6 cases were CD57 ⁺, 3 cases were TCRα/β ⁺, and 3 cases were TCRγ/δ ⁺. TCRG rearrangement was detected in 5 cases.The median follow-up time was 55(4-87) months, one patient died of heart disease, and the other 6 patients are surviving. CONCLUSION The incidence of T-LGLL is low. The initial symptoms of T-LGLL include anemia, fatigue, lymph node enlargement, splenomegaly, and higher percentage of lymphocytes in peripheral blood, the percentage of abnormal T cells in bone marrow was significantly increased. Analysis of flow cytometric immunophenotyping, TCR gene rearrangement, and hot spot genes such as STAT3 and STAT5b, can improve the diagnostic accuracy.
Humans ; Leukemia, Large Granular Lymphocytic/diagnosis* ; Male ; Middle Aged ; Female ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; Retrospective Studies

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

BACKGROUND: Acupuncture has shown potential therapeutic benefits for individuals with simple obesity. However, some researchers argue that some of the effectiveness of acupuncture may be due to the placebo response. OBJECTIVE: To understand the placebo response of acupuncture treatment in simple obesity, a systematic review and meta-analysis was designed based on the comparison between sham acupuncture before and after treatment. SEARCH STRATEGY: Eight databases (PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Database, China Biology Medicine Database, and Chinese Scientific Journals Database) were searched from inception to August 1, 2023. The MeSH search terms comprised obesity and acupuncture. INCLUSION CRITERIA: Randomized controlled trials (RCTs) using sham or placebo acupuncture as a control in treating obesity were enrolled. DATA EXTRACTION AND ANALYSIS: Two researchers independently extracted data, and the results were cross-checked after completion. Each RCT's detailed sham/placebo acupuncture treatment protocol was assessed according to the SHam Acupuncture REporting guidelines. The revised Cochrane risk-of-bias tool for randomized trials and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system were used to determine the risk of bias and quality of evidence, respectively. Body mass index (BMI) was defined as the primary outcome. Anthropometric parameters and laboratory test parameters related to obesity were defined as secondary outcomes. We used standardized mean difference (SMD) with 95% confidence interval (CI) to calculate treatment effects of outcomes. RESULTS: Fifteen RCTs with a total of 1250 patients were included. The BMI significantly decreased after treatment in the sham acupuncture group compared to baseline (SMD 0.37, 95% CI 0.09-0.66; I² = 81%, random model; P < 0.01). Treatment duration (P = 0.02) and other interventions significantly impacted the placebo response rate (P = 0.00). CONCLUSION The placebo response of sham acupuncture was strong in the RCTs for simple obesity, and the effect sizes differed between various outcomes. The treatment duration and other interventions emerged as potential influencing factors for the placebo response of sham acupuncture. Please cite this article as: Liu KJ, Jiao RM, Ji J, Yao WW, Han CR, Zhao XY, Zhao JJ. Placebo response in sham acupuncture therapy trials for simple obesity: a systematic review and meta-analysis. J Integr Med. 2025; 23(3): 264-273.
Humans ; Acupuncture Therapy/methods* ; Obesity/therapy* ; Placebo Effect ; Placebos ; Randomized Controlled Trials as Topic

Objective: Hypertrophy ligamentum flavum (LFH) is a common cause of lumbar spinal stenosis, resulting in significant disability and morbidity. Although long noncoding RNAs (lncRNAs) have been associated with various biological processes and disorders, their involvement in LFH remains not fully understood. Methods: Human ligamentum flavum samples were analyzed using lncRNA sequencing followed by validation through quantitative real-time polymerase chain reaction. To explore the potential biological functions of differentially expressed lncRNA-associated genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. We also studied the impact of lncRNA PARD3-AS1 on the progression of LFH in vitro. Results: In the LFH tissues when compared to that in the nonhypertrophic ligamentum flavum (LFN) tissues, a total of 1,091 lncRNAs exhibited differential expression, with 645 upregulated and 446 downregulated. Based on GO analysis, the differentially expressed transcripts primarily participated in metabolic processes, organelles, nuclear lumen, cytoplasm, protein binding, nucleic acid binding, and transcription factor activity. Moreover, KEGG pathway analysis indicated that the differentially expressed lncRNAs were associated with the hippo signaling pathway, nucleotide excision repair, and nuclear factor-kappa B signaling pathway. The expression of PARD3-AS1, RP11-430G17.3, RP1-193H18.3, and H19 was confirmed to be consistent with the sequencing analysis. Inhibition of PARD3-AS1 resulted in the suppression of fibrosis in LFH cells, whereas the overexpression of PARD3-AS1 promoted fibrosis in LFH cells in vitro. Conclusion This study identified distinct expression patterns of lncRNAs that are linked to LFH, providing insights into its underlying mechanisms and potential prognostic and therapeutic interventions. Notably, PARD3-AS1 appears to play a significant role in the pathophysiology of LFH.