Diagnostic value and cognitive regulatory roles of long non-coding RNA UCA1 in Alzheimer's disease.

BACKGROUND: To explore the diagnostic role and potential mechanism of serum lncRNA UCA1 in Alzheimer's disease (AD). METHODS: UCA1 concentration was determined using quantitative RT-PCR. The receiver operating characteristic curve was plotted to assess the diagnostic value. Cell viability and apoptotic capacity were assessed by cell counting kit-8 (CCK-8) and flow cytometry. Water maze experiments were used to test cognitive function in mice. The target genes of UCA1 were identified with a dual luciferase reporter assay. Functional and pathway analysis of miR-342-3p target genes was determined using enrichment analysis. RESULTS: The concentration of UCA1 was elevated in the AD group and represented a diagnostic possibility of AD. The silenced UCA1 reduced the roles of Aß on viability and apoptosis of SH⁃SY5Y cells by sponging miR-342-3p. The impaired cognitive impairment was partly recovered by the knockdown of the UCA1/miR-342-3p axis. Potential targets of miR-342-3p were enriched in function and pathways related to AD progression. CONCLUSION: The UCA1/miR-342-3p axis contributed to the occurrence of AD by regulating cognitive ability.

Geodetector analysis of individual and joint impacts of natural and human factors on maternal and child health at the provincial scale.

This ecological study examined the individual and joint impacts of natural-human factors on the spatial patterns of maternal and child health status in China at the provincial scale in 2020. We considered natural factors (forest coverage, average temperature, and total sulfur dioxide and particulate matter emissions) and human factors (economic development, urbanization, healthcare access, and education level). We combined maternal, infant, and under-five mortality rates into a composite maternal and child health index using the entropy method. The spatial autocorrelation analysis of this index highlighted distinct health patterns across provinces, whereas the geodetector method assessed the effects of natural-human factors on the patterns. A notable east-central-west stepwise decline in health status was observed. Global Moran's I showed positive spatial clustering, with high-high clustering areas in the Yangtze River Delta and low-low clustering areas in western regions. Factor detection identified eight significant natural-human factors impacting maternal and child health, with total sulfur dioxide emission density having the greatest impact. The interaction between average schooling years and total sulfur dioxide emission notably affected maternal and child health patterns. The study concludes that natural-human factors critically affect the spatial distribution of maternal and child health.

Neuropsychiatric disorders associated with recreational nitrous oxide use.

BACKGROUND: Recreational nitrous oxide use has grown in popularity among young people and has become a serious public health problem. Chronic use of nitrous oxide can lead to a functional vitamin B12 deficiency and neuropsychiatric complications. PURPOSE: This study aimed to investigate the characteristics of neuropsychiatric complications associated with nitrous oxide use and to enhance clinicians' awareness of this public health problem. METHODS: We retrospectively reviewed 16 patients with neuropsychiatric disorders related to nitrous oxide use who were treated in our hospital from June 2021 to October 2022. Their demographics, clinical features, investigations, treatments and outcomes were analyzed. RESULTS: There were ten males and six females between the ages of 17 and 25 with a mean age of 20.5 ± 2.6 years. Thirteen patients sought medical help from the neurology clinic. Two patients presented to the psychiatric department and one patient presented to the emergency department with acute cognitive impairment. All 16 patients presented with neurological symptoms, such as paresthesia in four limbs or the lower limbs, unsteady gait and weakness. Twelve patients developed psychiatric symptoms, such as hallucinations, agitation, depression, emotional indifference and personality changes. Twelve patients had vitamin B12 deficiency. All 16 patients had hyperhomocysteinemia. Fourteen patients showed abnormal high signal on T2-weighted imaging and an inverted "V" sign in axial view, mainly involving the cervical cord. Neuropsychiatric symptoms improved with vitamin B12 treatment and cessation of nitrous oxide use in all cases. CONCLUSION: Young adults are predominately involved in recreational use of nitrous oxide, which can cause neuropsychiatric complications. The clinical response to vitamin B12 supplementation and cessation of nitrous oxide use is generally good. Clinicians should recognize nitrous oxide use as a public health problem and a cause of a wide range of neuropsychiatric symptoms, particularly in younger patients.

Camel milk peptides alleviate hyperglycemia by regulating gut microbiota and metabolites in type 2 diabetic mice.

This study aimed to investigate the hypoglycemic effect of Camel milk peptides (CMPs) on Type 2 diabetes mellitus (T2DM) mice and reveal its related mechanism from the aspect of gut microbiota and metabolites. The administering CMPs significantly alleviated the weight loss, polydipsia and polyphagia, reduced fasting blood glucose (FBG), improved insulin resistance and sensitivity, and restored the level of serum hormones, lipopolysaccharide (LPS), lipid metabolic and tissue damage. Furthermore, CMPs intervention remarkably reversed gut microbiota dysbiosis in T2DM mice by reducing the relative abundance of Proteobacteria, Allobaculum, Clostridium, Shigella and the Firmicutes/Bacteroidetes ratio, while increasing the relative abundance of Bacteroidetes and Blautia. Metabolomic analysis identified 84 different metabolites between T2DM and CMPs-treated groups, participating in three pathways of Pantothenate and CoA biosynthesis, Phenylalanine metabolism and Linoleic acid metabolism. Ureidopropionic acid, pantothenic acid, hippuric acid, hydrocinnamic acid and linoleic acid were identified as key acidic metabolites closely related to hypoglycemic effect. Correlation analysis indicated that CMPs might have a hypoglycemic effect through their impact on gut microbiota, leading to variations in short-chain fatty acids (SCFAs), acidic metabolites and metabolic pathways. These findings suggest that CMPs could be a beneficial nutritional supplement for intervention T2DM.

Harvest and Primary Culture of Leptomeningeal Lymphatic Endothelial Cells.

Leptomeningeal lymphatic endothelial cells (LLECs) are a recently discovered intracranial cellular population with a unique distribution clearly distinct from peripheral lymphatic endothelial cells. Their cellular function and clinical implications remain largely unknown. Consequently, the availability of a supply of LLECs is essential for conducting functional research in vitro. However, there is currently no existing protocol for harvesting and culturing LLECs in vitro. This study successfully harvested LLECs using a multi-step protocol, which included coating the flask with fibronectin, dissecting the leptomeninges with the assistance of a microscope, enzymatically digesting the leptomeninges to prepare a single-cell suspension, inducing the expansion of LLECs with vascular endothelial growth factor-C (VEGF-C), and selecting lymphatic vessel hyaluronic receptor-1 (LYVE-1) positive cells through magnetic-activated cell sorting (MACS). This process ultimately led to the establishment of a primary culture. The purity of the LLECs was confirmed through immunofluorescence staining and flow cytometric analysis, with a purity level exceeding 95%. This multi-step protocol has demonstrated reproducibility and feasibility, which will greatly facilitate the exploration of the cellular function and clinical implications of LLECs.

In situ preparation of double gradient anode materials based on polysiloxane for lithium-ion batteries.

Although silicon has a high volumetric energy density as an anode material for Li-ion batteries, its volumetric expansion and sluggish Li+ migration kinetics need to be urgently addressed. In this work, cage-like structure materials (HRPOSS) derived from the in situ hydrogen reduction of polyhedral oligomeric silsesquioxane (T8-type POSS) were constructed as an Si@C anode for Li-ion batteries. Benefiting from the intriguing features of the Si/N double gradient and even-distributed silicon, HRPOSS-6 exhibited faint volume changes and fast ion-electron kinetics. Moreover, the uniformly immobilized nano-silicic and concentration gradient were favorable for accelerated ion migration. Therefore, HRPOSS-6 exhibited good electrochemical performances given that its cage structure could relieve the volume expansion. HRPOSS-6 demonstrated a high reversible capacity of 1814.1 mA h g-1 and long cycling performance after 200 cycles with 635 mA h g-1 at a current density of 0.5 A g-1. Accordingly, this Si/C/N composite exhibited great potential for high energy Li-ion batteries, where the corresponding full-cell (HRPOSS-6//LiNi0.6Co0.2Mn0.2O2) showed a cycle life of 200 cycles with over 80% capacity retention at rate of 1C. This work exploits the concentration gradients of dual elements for the capacity improvement of Si anodes and offers insight into the development of high-performance Si@C anode materials for advanced Li-ion batteries.

Imaging Vital and Non-vital Brain Pericytes in Brain Slices following Subarachnoid Hemorrhage.

Pericytes are crucial mural cells situated within cerebral microcirculation, pivotal in actively modulating cerebral blood flow via contractility adjustments. Conventionally, their contractility is gauged by observing morphological shifts and nearby capillary diameter changes under specific circumstances. Yet, post-tissue fixation, evaluating vitality and ensuing pericyte contractility of imaged brain pericytes becomes compromised. Similarly, genetically labeling brain pericytes falls short in distinguishing between viable and non-viable pericytes, particularly in neurologic conditions like subarachnoid hemorrhage (SAH), where our preliminary investigation validates brain pericyte demise. A reliable protocol has been devised to surmount these constraints, enabling simultaneous fluorescent tagging of both functional and non-functional brain pericytes in brain sections. This labeling method allows high-resolution confocal microscope visualization, concurrently marking the brain slice microvasculature. This innovative protocol offers a means to appraise brain pericyte contractility, its impact on capillary diameter, and pericyte structure. Investigating brain pericyte contractility within the SAH context yields insightful comprehension of its effects on cerebral microcirculation.

Reliability analysis of s-out-of-k multicomponent stress-strength system with dependent strength elements based on copula function.

This paper considers the reliability analysis of a multicomponent stress-strength system which has $k$ statistically independent and identically distributed strength components, and each component is constructed by a pair of statistically dependent elements. These elements are exposed to a common random stress, and the dependence among lifetimes of elements is generated by Clayton copula with unknown copula parameter. The system is regarded to be operating only if at least $s$($1 \leq s \leq k$) strength variables in the system exceed the random stress. The maximum likelihood estimates (MLE) of unknown parameters and system reliability is established and associated asymptotic confidence interval is constructed using the asymptotic normality property and delta method, and the bootstrap confidence intervals are obtained using the sampling theory. Finally, Monte Carlo simulation is conducted to support the proposed model and methods, and one real data set is analyzed to demonstrate the applicability of our study.

The comparison of two different strategies of intravitreal conbercept for polypoidal choroidal vasculopathy in Chinese patients results from a 48-week randomized phase 4 study: STAR study.

PURPOSE: To compare a treat-and-extend (TAE) strategy with a fixed dosing regimen of intravitreal conbercept (IVC) for the management of treatment-naïve polypoidal choroidal vasculopathy (PCV) patients. METHODS: 249 patients with treatment-naïve PCV were randomized 1:1 to fixed dosing regimen with injections every 12 weeks (3 + Q12W) group or treat-and-extend regimen(3 + TAE) group. Patients received 3 monthly intravitreal injections of 0.5 mg conbercept as loading dose in both groups. The 3 + Q12W patients were monitored monthly and received mandated injections every 12 weeks; the 3 + TAE patients were monitored and treated monthly until the resolution of exudative disease activity; the interval between visits was then individualized according to study protocol. Visual and anatomical outcomes were compared between the two groups. RESULTS: At 48 weeks, there was no significant difference between the 3 + Q12W group and 3 + TAE group in mean BCVA improvement (p = 0.421), mean changes in central retinal thickness (CRT) (p = 0.818), maximum retinal thickness (MRT) (p = 0.448), pigment epithelial detachment (PED) height (p = 0.221), PED volume (p = 0.076), branching vascular network (BVN) area (p = 0.615), polypoidal lesion number (p = 0.701), polypoidal lesion area (p = 0.424), rates of patients who avoided vision loss of ≥15 ETDRS letters (p = 0.397) or complete polypoidal lesion regression rate (43.8% vs. 41.8%, p = 0.814). The 3 + Q12W group had more decreased retinal haemorrhage area (p = 0.014) and fewer mean numbers of injections comparing with 3 + TAE group (6.6 vs. 9.4, p < 0.001). Mean maximum extension interval between injections after loading injections was 9.6 ± 2.0 weeks for 3 + TAE group, with 27.8% of patients achieving an extension interval of 12 weeks and 61.1% patients 8 weeks or more. CONCLUSIONS: Both 3 + Q12W and 3 + TAE regimens of IVC could result in improvement in visual and anatomical outcomes in PCV patients.

Assessment of Hematologic and Biochemical Parameters for Healthy Commercial Pigs in China.

Hematologic and biochemical data are useful for indicating disease diagnosis and growth performance in swine. However, the assessment of these parameters in healthy commercial pigs is rare in China. Thus, blood samples were collected from 107 nursery pigs and 87 sows and were analyzed for 25 hematologic and 14 biochemical variables. After the rejection of the outliers and the detection of the data distribution, the correlations between the blood parameters were analyzed and the hematologic/biochemical RIs were preliminarily established using the 95% percentile RI. Correlation analysis showed that albumin was the hub parameter among the blood parameters investigated, and genes overlapping with key correlated variables were discovered. Most of the hematologic and biochemical parameters were significantly different between nursery pigs and sows. The 95% RIs of white blood cells and red blood cells were 7.18-24.52 × 109/L and 5.62-7.84 × 1012/L, respectively, for nursery pigs, but 9.34-23.84 × 109/L and 4.98-8.29 × 1012/L for sows. The 95% RIs of total protein and albumin were 43.16-61.23 g/dL and 19.35-37.86 g/dL, respectively, for nursery pigs, but 64.96-88.68 g/dL and 31.91-43.28 g/dL for sows. In conclusion, our study highlights the variability in blood parameters between nursery pigs and sows and provides fundamental data for the health monitoring of commercial pigs in China.

Heroin Addiction Induces Axonal Transport Dysfunction in the Brain Detected by In Vivo MRI.

Heroin is a highly addictive drug that causes axonal damage. Here, manganese-enhanced magnetic resonance imaging (MEMRI) was used to dynamically monitor axonal transport at different stages of heroin addiction. Rat models of heroin addiction (HA) and prolonged heroin addiction (PHA) were established by injecting rats with heroin at different stages. Heroin-induced learning and memory deficits were evaluated in the Morris water maze (MWM), and MEMRI was used to dynamically evaluate axonal transport in the olfactory pathway. The expression of proteins related to axonal structure and function was also assessed by Western blotting. Transmission electron microscopy (TEM) was used to observe ultrastructural changes, and protein levels of neurofilament heavy chain (NF-H) were analyzed by immunofluorescence staining. HA rats, especially PHA rats, exhibited worse spatial learning and memory than control rats. Compared with HA rats and control rats, PHA rats exhibited significantly longer escape latencies, significantly fewer platform-location crossings, and significantly more time in the target quadrant during the MWM test. Mn2+ transport was accelerated in HA rats. PHA rats exhibited severely reduced Mn2+ transport, and the axonal transport rate (ATR) was significantly lower in these rats than in control rats (P < 0.001). The levels of cytoplasmic dynein and kinesin-1 were significantly decreased in the PHA group than in the control group (P < 0.001); additionally, the levels of energy-related proteins, including cytochrome c oxidase (COX) IV and ATP synthase subunit beta (ATPB), were lower in the PHA group (P < 0.001). The brains of heroin-exposed rats displayed an abnormal ultrastructure, with neuronal apoptosis and mitochondrial dysfunction. Heroin exposure decreased the expression of NF-H, as indicated by significantly reduced staining intensities in tissues from HA and PHA rats (P < 0.05). MEMRI detected axonal transport dysfunction caused by long-term repeated exposure to heroin. The main causes of axonal transport impairment may be decreases in the levels of motor proteins and mitochondrial dysfunction. This study shows that MEMRI is a potential tool for visualizing axonal transport in individuals with drug addictions, providing a new way to evaluate addictive encephalopathy.

Exosomal Dvl3 promoted the aggressive phenotypic transformation of RA-FLS via wnt pathway.

OBJECTIVE: This study was performed to explore the function and mechanism of Dvl3 in RA-FLS by exosome intervention. METHODS: The expression pattern of Dvl3 was examined by IHC, WB, and qPCR. Modified exosomes obtained from culturing supernatant of RA-FLS infected with Dvl3 over expression (OE) lentivirus were administrated to the target RA-FLS. The ability of survival, migration, and the production of inflammatory factor influenced by exosomal Dvl3 were detected by CKK8 kits, Tunel, migration test, qPCR, and enzyme-linked immunosorbent assay (ELISA) respectively; Flow cytometry analysis was conducted to explorer the inflammatory moderate role of exosomes on CD4+ T cells. The possible downstream pathways of Dvl3 were screened by qPCR and WB and verified by double luciferase reporter experiment. RESULTS: The expression level of Dvl3 was significantly increased in RA and CIA. Exosomes from the OE group could significantly promote cell proliferation activity, migration/invasion ability. The augment of TNF-α, IL-1ß, IL-17, and IL-21 was observed in exosomal Dvl3-OE group. Th1 and Th17 cells polarisation and cytokines related were both enhanced by Exosomal Dvl3. Over expression of Dvl3 was accompanied by the significant increase of ß-catenin and RhoA activities. CONCLUSION: This study discovered the high expression of Dvl3 of exosomes derived from RA patients which may possessed the ability to promote phenotypic transformation of RA-FLS through Wnt pathway.

Photoinduced Silylation of N-Heteroarenes and Unsaturated Benzamides with Naphthalimide-Based Organic Photocatalysts.

Described herein is the development of a general strategy for the silylation of N-heteroaromatics and unsaturated benzamides via the rational designing of an efficient organic photocatalyst. The process features operational simplicity, mild reaction conditions, and the use of readily prepared naphthalimide (NI)-based organic photocatalysts. Notably, both inert trialkylhydrosilanes and arylhydrosilanes are well tolerated with this protocol.

Metformin modulates microbiota-derived inosine and ameliorates methamphetamine-induced anxiety and depression-like withdrawal symptoms in mice.

BACKGROUND: Metformin exhibits therapeutic potential in behavioural deficits induced by methamphetamine (METH) in rats. Emerging studies suggest gut microbiota may impact psychiatric symptoms, but there is no direct evidence supporting metformin's participation in the pathophysiology of withdrawal symptoms via modulation of gut microbiota. METHODS: In order to define the functional impacts of gut microbiota and metformin to the behavioural deficits during METH withdrawal, we utilized a combination of fecal microbiota transplantation (FMT), high-throughput sequencing, and untargeted metabolomics technologies. RESULTS: First, METH addicts exhibited higher α diversity and distinct microbial structures compared to healthy controls. In particular, the relative abundance of Rikenellaceae was positively correlated with the severity of anxiety and depression. Second, both human-to-mouse and mouse-to-mouse FMTs confirmed that METH-altered-microbiota transplantation is sufficient to promote anxiety and depression-like behaviours in recipient germ-free mice, and these behavioural disturbances could be ameliorated by metformin. In-depth analysis revealed that METH significantly altered the bacterial composition and structure as well as relative abundance of several bacterial taxa and metabolites, including Rikenellaceae and inosine, respectively, whereas add-on metformin could remodel these alterations. Finally, the inosine complementation successfully restored METH-induced anxiety and depression-like behaviours in mice. CONCLUSION: This study demonstrates that METH withdrawal-induced anxiety and depression-like behaviours are reversible and transmissible via gut microbiota in a mouse model. The therapeutic effects of metformin on psychiatric manifestations are associated with microbiota-derived metabolites, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.

Quercetin Mitigates Methamphetamine-Induced Anxiety-Like Behavior Through Ameliorating Mitochondrial Dysfunction and Neuroinflammation.

Methamphetamine (MA) abuse results in neurotoxic outcomes, including increased anxiety and depression. Studies have reported an association between MA exposure and anxiety, nonetheless, the underlying mechanism remains elusive. In the present study, we developed a mouse model of anxiety-like behavior induced by MA administration. RNA-seq was then performed to profile the gene expression patterns of hippocampus (HIPP), and the differentially expressed genes (DEGs) were significantly enriched in signaling pathways related to psychiatric disorders and mitochondrial function. Based on these, mitochondria was hypothesized to be involved in MA-induced anxiety. Quercetin, as a mitochondrial protector, was used to investigate whether to be a potential treatment for MA-induced anxiety; accordingly, it alleviated anxiety-like behavior and improved mitochondrial impairment in vivo. Further experiments in vitro suggested that quercetin alleviated the dysfunction and morphological abnormalities of mitochondria induced by MA, via decreasing the levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and increasing the oxygen consumption rate (OCR) and ATP production. Moreover, the study examined the effect of quercetin on astrocytes activation and neuroinflammation, and the results indicated that it significantly attenuated the activation of astrocytes and reduced the levels of IL-1ß, TNFα but not IL-6. In light of these findings, quantitative evidence is presented in the study supporting the view that MA can evoke anxiety-like behavior via the induction of mitochondrial dysfunction. Quercetin exerted antipsychotic activity through modulation of mitochondrial function and neuroinflammation, suggesting its potential for further therapeutic development in MA-induced anxiety.

Outcomes and risk factors of perforating and non-perforating middle cerebral artery infarctions after intravenous thrombolysis.

The clinical symptoms of perforating arteries differ, and responses to intravenous thrombolytic therapy are heterogeneous. Here, we investigated the effect of intravenous thrombolytic therapy and the related factors influencing acute perforating and non-perforating middle cerebral artery infarctions. We analyzed 320 patients with acute middle cerebral artery infarction who received alteplase thrombolysis within 4.5 h of onset at two stroke centers from January 2016 to December 2019. Outcome measures included rates of a favorable functional outcome (modified Rankin Scale scores of 0-2), distribution of modified Rankin Scale scores, intracranial hemorrhage, and symptomatic cerebral hemorrhage at 14 days, with comparisons between perforating artery and non-perforating artery cerebral infarction groups. In the perforating vessel disease group, 12 cases (17.4%) of intracranial hemorrhage occurred, with symptomatic cerebral hemorrhage in three cases (4.3%); there were no significant differences between the perforating and non-perforating vessel disease groups (all P > 0.05). In the perforating vessel disease group, the only significant prognostic factor was the National Institutes of Health Stroke Scale score before thrombolysis (Exp(B) = 1.365; 95% confidence interval [CI] 1.124-1.659; P = 0.002), and the only significant risk factor for hemorrhagic transformation was previous perforator disease (Exp(B) = 0.078; P = 0.038). Regardless of whether an acute infarction is perforating or non-perforating, intravenous thrombolytic therapy can yield a favorable outcome. Therefore, intravenous thrombolysis should be actively administered to treat perforating artery infarctions with a high risk of disability.

Contribution of the mutation rs8193069 in TLR4 to mastitis resistance and performance in Holstein cows in southern China.

Bovine mastitis has become increasingly important issues for farmers and consumers, leading to large economic losses in the dairy industry worldwide. Because treatment of mastitis is difficult and costly, improved mastitis resistance through selective breeding would be advantageous. The toll-like receptor 4 (TLR4) is an important player in recognising pathogens and activating immune responses. However, its roles in mastitis occurrence and the underlying molecular mechanisms are unclear. In this study, a single nucleotide polymorphism, rs8193069 (T â†’ C) in TLR4 gene was detected in a Holstein cow resource population in southern China. Association analysis with 5-year production traits, haematology, and biochemistry parameters revealed that individuals with genotype CC had significantly lower somatic cell counts (SCC), lower fat percentage, but higher 305-day milk (p < 0.05) and total milk yield (p < 0.01). Both genotypes CC and CT had lower lymphocyte counts (#LYMPH) (p < 0.01) and basophil counts (#BASO) (p < 0.05) than TT. Genotype CC had a less level of triglyceride (p < 0.01) and creatine kinase (p < 0.05) than CT. Further analysis based on the production data revealed significant positive correlations between SCC and #LYMPH. Analysis of TLR4 protein structure and properties suggested that the missense mutation on the 674th amino acid from Thr to Ile reduced the flexibility and hydrophilicity of TIR domain, implying a weakened binding ability of TLR4 to its adaptors. In conclusion, allele C of rs8193069 was the major allele in Holstein cows that indicated a greater genetic potential to mastitis resistance and milk yields, probably via the LPS-TLR4 inflammatory signalling. This study offers a marker to improve mastitis resistance in the dairy cow population in southern China.

A Chemoenzymatic Cascade Combining a Hydration Catalyst with an Amine Dehydrogenase: Synthesis of Chiral Amines.

The combination of biocatalysis and transition-metal catalysis can complement synthetic gaps only in a chemical or biological process. However, the intrinsic mutual deactivation between enzymatic and chemical species is a significant challenge in a single operation. To address the above issue, we developed an encapsulated Au/carbene combined with a free amine dehydrogenase as a co-catalyst system that enables an efficient hydration/amination enantioselective cascade process to be accomplished. The mechanistic investigation discloses dual catalysis comprised of alkyne hydration, followed by a reductive amination process.

Integration of Molecular Inflammatory Interactome Analyses Reveals Dynamics of Circulating Cytokines and Extracellular Vesicle Long Non-Coding RNAs and mRNAs in Heroin Addicts During Acute and Protracted Withdrawal.

Heroin addiction and withdrawal influence multiple physiological functions, including immune responses, but the mechanism remains largely elusive. The objective of this study was to investigate the molecular inflammatory interactome, particularly the cytokines and transcriptome regulatory network in heroin addicts undergoing withdrawal, compared to healthy controls (HCs). Twenty-seven cytokines were simultaneously assessed in 41 heroin addicts, including 20 at the acute withdrawal (AW) stage and 21 at the protracted withdrawal (PW) stage, and 38 age- and gender-matched HCs. Disturbed T-helper(Th)1/Th2, Th1/Th17, and Th2/Th17 balances, characterized by reduced interleukin (IL)-2, elevated IL-4, IL-10, and IL-17A, but normal TNF-α, were present in the AW subjects. These imbalances were mostly restored to the baseline at the PW stage. However, the cytokines TNF-α, IL-2, IL-7, IL-10, and IL-17A remained dysregulated. This study also profiled exosomal long non-coding RNA (lncRNA) and mRNA in the plasma of heroin addicts, constructed co-expression gene regulation networks, and identified lncRNA-mRNA-pathway pairs specifically associated with alterations in cytokine profiles and Th1/Th2/Th17 imbalances. Altogether, a large amount of cytokine and exosomal lncRNA/mRNA expression profiling data relating to heroin withdrawal was obtained, providing a useful experimental and theoretical basis for further understanding of the pathogenic mechanisms of withdrawal symptoms in heroin addicts.