Activation of endogenous retrovirus triggers microglial immuno-inflammation and contributes to negative emotional behaviors in mice with chronic stress.

BACKGROUND: The "missing" link of complex and multifaceted interplay among endogenous retroviruses (ERVs) transcription, chronic immuno-inflammation, and the development of psychiatric disorders is still far from being completely clarified. The present study was aimed to investigate the mechanism of protective role of inhibiting ERVs on reversing microglial immuno-inflammation in basolateral amygdala (BLA) in chronic stress-induced negative emotional behaviors in mice. METHODS: Male C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) for 6 w. Negative emotional behaviors were comprehensively investigated to identify the susceptible mice. Microglial morphology, ERVs transcription, intrinsic nucleic acids sensing response, and immuno-inflammation in BLA were assessed. RESULTS: Mice with chronic stress were presented as obviously depressive- and anxiety-like behaviors, and accompanied with significant microglial morphological activation, murine ERVs genes MuERV-L, MusD, and IAP transcription, cGAS-IFI16-STING pathway activation, NF-κB signaling pathway priming, as well as NLRP3 inflammasome activation in BLA. Antiretroviral therapy, pharmacological inhibition of reverse transcriptases, as well as knocking-down the ERVs transcriptional regulation gene p53 significantly inhibited microglial ERVs transcription and immuno-inflammation in BLA, as well as improved the chronic stress-induced negative emotional behaviors. CONCLUSIONS: Our results provided an innovative therapeutic approach that targeting ERVs-associated microglial immuno-inflammation may be beneficial to the patients with psychotic disorders.

Astragaloside IV inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes.

Loss of podocytes is a hallmark of diabetic nephropathy, and a growing body of evidence indicates that podocytes are susceptible to palmitic acid (PA). We have previously shown that AS-IV inhibited PA-induced podocyte apoptosis by activating sarcoendoplasmic reticulum Ca2+ ATPase (SERCA), which indicate calcium regulation may involve in the process. Immunofluorescence staining, Western blot and flow cytometry were used to measure the protective efficacy of AS-IV to ameliorate PA-induced ER stress and podocyte apoptosis. Meanwhile, AS-IV inhibited cytochrome c release, decreased mitochondrial membrane potential, accompany with the depletion of endoplasmic reticulum Ca2+ and elevation of cytosolic and mitochondrial Ca2+. Sequestration of cytosolic calcium with BAPTA-AM limited the response of podocyte apoptosis, while during the process the effect of AS-IV was also restrained. In contrast, elevation of cytosolic calcium with calcium ionophore ionomycin was depressed by AS-IV addition. Furthermore, inhibiting TRPC6 expression with SKF96365 or TRPC6 siRNA counteracted the beneficial effect of AS-IV. Our study provides further evidence to conclude the inhibitory effect of AS-IV to podocyte apoptosis is Ca2+-dependent. And the efficacy correlates with inhibiting TRPC6-mediated Ca2+ influx, and then cellular Ca2+ disturbance was coordinated.

Alpha- and gamma-mangostins exhibit anti-acne activities via multiple mechanisms.

Objective: Acne is a chronic skin disease that involves four key pathogenic factors: excess sebum production, ductal epidermal hyperproliferation, Propionibacterium acnes (P. acnes) colonization, and skin inflammation. Mangostins are well-known for their anti-bacterial and anti-inflammatory effects, suggesting that mangostins may have therapeutic potential for acne. The present study aimed to explore the anti-acne effects of mangostins from the perspective of multiple pathogenic mechanisms of acne. Methods: The effects of α- and γ-mangostins on the growth of P. acnes and lipase activity were analyzed. Their effects on P. acnes-induced keratinocyte proliferation were examined by CCK-8. The expression of inflammatory genes and activation of NF-κB and MAPK signaling pathways were detected by quantitative real-time PCR and western blotting, respectively. Results: Alpha- and γ-mangostins not only inhibited the growth of P. acnes, but also reduced the proliferation of keratinocytes induced by heat-killed P. acnes. Furthermore, α- and γ-mangostins were able to suppress P. acnes-induced expression of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6 in keratinocytes by inhibiting the activation of NF-κB and MAPK signaling pathways. Discussion and conclusions: Mangostins appeared to possess multiple anti-acne activities, including the inhibition of P. acnes growth, regulation of keratinocytes proliferation, and attenuation of skin inflammatory reaction. Hence, mangostins might be developed into a potential therapeutic agent for the treatment of acne.

Comparison of photoemission characteristics between square and circular wire array GaAs photocathodes.

Two types of negative electron affinity gallium arsenide (GaAs) wire array photocathodes were fabricated by reactive ion etching and inductively coupled plasma etching of bulk GaAs material. High density GaAs wire arrays with high periodicity and good morphology were verified using scanning electron microscopy, and photoluminescence spectra confirmed the wire arrays had good crystalline quality. Reflection spectra showed that circular GaAs wire arrays had superior light trapping compared with square ones. However, after Cs/O activation, the square GaAs wire array photocathodes showed enhanced spectral response. The integral sensitivity of the square wire array photocathodes was approximately 2.8 times that of the circular arrays.

Dynamics of graded-composition and graded-doping semiconductor nanowires under local carrier modulation.

Scanning photocurrent microscopy is a powerful tool for investigating charge transfer and internal fields, which strongly influence carrier statics and dynamics in semiconductor nanowires. We performed comprehensive numerical modeling of the carrier dynamics of graded-composition and graded-doping AlGaAs nanowires to achieve a greater understanding of these nanowires. The simulation results indicated that the built-in electric field changes the shape of the scanning photocurrent microscopy profiles, which helped us to judge the dopant level, Al composition range and doping type of the material. The simulation results also assess the potential of the scanning photocurrent techniques in graded-doping and graded-composition nanowire properties.

Negative electron affinity GaAs wire-array photocathodes.

Negative electron affinity GaAs wire-array photocathodes have been fabricated by reactive ion etching and inductively coupled plasma etching of bulk GaAs material followed by Cs-O activation. Scanning electron microscope has revealed that the thus obtained high-density GaAs wire arrays had high periodicity, large height, and good morphology. Photoluminescence spectra indicated the wire arrays were of good crystalline quality and free from any obvious damage. Compared to the original GaAs wafer, the photoluminescence peak positions of the wire arrays were somewhat red-shifted, which may be attributed to the temperature effect and strain relaxation. The wire-array structures showed significantly reduced light reflection compared with the original wafer due to the excellent light-trapping effect. Cs-O activation experiments of the GaAs wire arrays have been performed to reveal the effect of incident angle on quantum efficiency. The results show that maximum quantum efficiency was obtained at about 30°. Given these unique electrical and optical properties, a GaAs wire-array photocathode is an attractive alternative to its planar-structured counterpart.

Norisoboldine, an alkaloid from Radix linderae, inhibits NFAT activation and attenuates 2,4-dinitrofluorobenzene-induced dermatitis in mice.

CONTEXT: The nuclear factor of activated T-cells (NFAT) is a family of transcription factors, essential for T-cell activation. Norisoboldine (NOR), an isoquinoline alkaloid from Radix linderae, has been demonstrated to possess anti-inflammatory activity. OBJECTIVE: This study examines NOR's effect on NFAT activation and its therapeutic potential for atopic dermatitis (AD). MATERIALS AND METHODS: The transcriptional activity of NFAT was examined with luciferase reporter assay, using K562-luc cells, stimulated with 20 ng/mL PMA plus 1 µM ionomycin. NFAT dephosphorylation was examined by immuno-blotting in K562-luc cells and Jurkat cells. Interleukin-2 (IL-2) expression in Jurkat cells was examined by real-time PCR. A mouse model of dermatitis, induced by 2,4-dinitrochlorobenzene (DNCB), was used to test NOR's therapeutic potential for AD. RESULTS: NOR, dose-dependently, inhibited PMA and ionomycin-induced NFAT reporter gene expression in K562-luc cells in the range of 2-50 µM. NOR also inhibited PMA and ionomycin-induced NFAT dephosphorylation in K562-luc cells and Jurkat cells. Consequently, NOR suppressed PMA plus ionomycin-induced IL-2 expression in Jurkat cells. The administration of NOR (10 mg/kg, i.p.), alleviated DNCB-induced dermatitis in mice, by the reduction of ear swelling and attenuation of inflammatory infiltration into ear tissue. Moreover, mRNA levels of INF-γ, TNF-α, IL-4 and IL-6 in ears of NOR-treated mice were reduced by 78.4, 77.8, 72.3 and 73.9%, respectively, compared with untreated controls. DISCUSSION AND CONCLUSION: This study demonstrates that NOR inhibits NFAT activation in T-cells and alleviates AD-like inflammatory reaction in a DNCB-induced dermatitis model, highlighting NOR as a potential therapeutic agent for AD.

Effects of graded band-gap structures on spectral response of AlGaAs/GaAs photocathodes.

The effects of AlGaAs/GaAs layer thickness and Al composition range on the spectral response and integral sensitivities of reflection-mode graded band-gap AlGaAs/GaAs photocathodes have been investigated and simulated. The experimental results demonstrate that the spectral response over the wavelength region of interest for graded band-gap photocathodes is greater than that for uniform band-gap cathodes, and the increase in long-wavelength response is more pronounced. These results can be attributed to the built-in electric field in the graded band-gap AlGaAs layer. We established a spectral response model of graded band-gap photocathodes based on the numerical solution of coupled Poisson and continuity equations. According to the model, we calculated the theoretical spectral response and sensitivities of graded band-gap cathodes, and found the optimum Al(x)Ga(1-x)As layer thicknesses are 6, 10, 16, and 22 µm for the reflection-mode cathodes with linearly graded Al composition x ranges of 0 to 0.1, 0.2, 0.3, and 0.4, respectively.

Resolution characteristics of graded doping and graded composition transmission-mode AlGaAs/GaAs photocathodes.

The resolution model of a graded doping and graded composition transmission-mode AlGaAs/GaAs photocathode is solved numerically from the two-dimensional continuity equations. According to the model, we calculate the theoretical modulation transfer function (MTF) of different graded doping and graded composition structures. The simulation results show that both graded composition and graded doping structures can increase the resolution of the photocathode. The exponentially doping and linear composition photocathode has the maximum resolution among the possible graded doping and graded composition photocathodes. The resolution improvement is attributed to the built-in electric field induced by a graded composition or graded doping structure. The simulation results also show that the MTFs of AlGaAs/GaAs cathodes increase as the AlGaAs layer thickness decreases, or the incident light wavelength increases.

CircHIPK2 facilitates phenotypic switching of vascular smooth muscle cells in hypertension.

Hypertension is a clinical syndrome characterized by increased systemic arterial blood pressure, affecting about 1.4 billion people currently worldwide with only one in seven cases adequately controlled. It is the main contributing factor of cardiovascular diseases (CVDs), often co-existing with other CVDs risk factors to impair the structure and function of important organs such as heart, brain, and kidney, and ultimately lead to multi-organ failure. Vascular remodeling is a critical process in the development of essential hypertension, and phenotype switching of vascular smooth muscle cells (VSMCs) was reported contributing substantially to vascular remodeling. circHIPK2 is a circular RNA (circRNA) derived from the second exon of homeodomain-interacting protein kinase 2 (HIPK2). Several studies revealed that circHIPK2 functions in various diseases by serving as a microRNA (miRNA) sponge. However, the functional roles and molecular mechanisms of circHIPK2 in VSMC phenotype switching and hypertension are not clear. In the present study, we showed that the expression of circHIPK2 was significantly upregulated in the VSMCs of hypertensive patients. Functional studies showed that circHIPK2 promoted the Angiotensin II (AngII)-induced VSMC phenotype switching by acting as the sponge of miR-145-5p, thereby upregulating the expression of a disintegrin and metalloprotease (ADAM) 17. Collectively, our study provides a new therapeutic target for hypertension.

Energy distributions of electrons emitted from reflection-mode Cs-covered GaAs photocathodes.

By calculating the energy distributions of electrons reaching the photocathode surface and solving the Schrödinger equation for an electron tunneling through the surface potential barrier, we have obtained an equation to calculate the energy distributions of electrons emitted from reflection-mode Cs-covered GaAs photocathodes based on a two-minima diffusion model. According to the equation, we studied the effects of incident photon energies, diffusion lengths, and surface potential barrier on the electron energy distributions. The equation was also used to fit the measured electron energy distribution curves and the cathode performance parameters were obtained from the fitting. The Γ and L peaks in the theoretical curves are in agreement with the peaks in the experimental curves. The fitted barrier thickness 1.7 Å exactly reflects the GaAs-Cs dipole layer thickness.

Circ_0138959/miR-495-3p/TRAF6 axis regulates proliferation, wound healing and osteoblastic differentiation of periodontal ligament cells in periodontitis.

Background/purpose: Periodontitis is a chronic inflammatory disease, and periodontal ligament cells (PDLCs) are pivotal for osteogenesis. Circular RNAs (circRNAs) can regulate disease progression via targeting miRNA/mRNA axis. The purposes of this study were to explore the function and mechanism of circ_0138959 in periodontitis. Materials and methods: Periodontitis cell model was established by lipopolysaccharide (LPS) treatment in PDLCs. RNA expression was determined by quantitative reverse transcription-polymerase chain reaction assay. Cell proliferation was detected using 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide assay. Wound healing and cell apoptosis were examined by wound healing assay and flow cytometry. Inflammatory cytokines were measured via Enzyme-linked immunosorbent assay. Osteogenic differentiation was assessed by Alkaline phosphatase and Alizarin red S staining assays. Western blot was used for protein detection. The target interaction was validated by dual-luciferase reporter assay. Results: Circ_0138959 was overexpressed in periodontitis tissues and LPS-treated PDLCs. Downregulation of circ_0138959 attenuated LPS-induced inhibition of proliferation, wound healing and osteogenic differentiation but promotion of apoptosis and inflammation. Circ_0138959 acted as a miR-495-3p sponge, and the regulatory role of circ_0138959 in LPS-induced cell injury was achieved by sponging miR-495-3p. Additionally, miR-495-3p targeted TNF Receptor Associated Factor 6 (TRAF6) and miR-495-3p protected against LPS-induced cell dysfunction by targeting TRAF6. Circ_0138959 upregulated TRAF6 level via inhibiting miR-495-3p. Conclusion: This study suggested that circ_0138959 upregulated the TRAF6 expression by binding to miR-495-3p, consequently aggravating LPS-induced cell damages in PDLCs. Circ_0138959 might be a probable target for treatment of periodontitis.

N6-Methyladenosine RNA Methylation in Cardiovascular Diseases.

N6-methyladenosine (m6A) modification is the most universal and abundant post-transcriptional modification of eukaryotic RNA and occurs mainly at the consensus motif RR (m6A) CH (R = A or G, H = A, C, or U) in long internal exons, near stop codons, or in the 3' untranslated region (UTR). "Writers," "erasers," and "readers" are responsible for the occurrence, removal, and recognition of m6A modification, respectively. Substantial evidence has shown that m6A RNA modification can exert important functions in physiological and pathological processes. Cardiovascular diseases (CVDs) are a wide array of disorders affecting heart or vessels, including atherosclerosis (AS), hypertension (HT), ischemia/reperfusion (I/R) injury, myocardial infarction (MI), stroke, cardiac hypertrophy, heart failure (HF), and so on. Despite the advances in lipid-lowering drugs, antihypertensives, antiplatelet agents, and anticoagulation therapy, CVDs are still the leading cause of death worldwide. Recent studies have suggested that m6A modification of RNA may contribute to the pathogenesis of CVDs, providing a novel research insight for CVDs. Herein, we provide an up-of-date summarization of the molecular mechanism of m6A and the roles of m6A in different types of CVDs. At last, we propose that m6A might be a potiential biomarker or therapeutic target for CVDs.

Application Value of Machine Learning Method in Measuring Gray Matter Volume of AIDS Patients.

Background: To investigate the role of gray matter (GM) volume in the identification of HIV-positive patients with HIV-associated neurocognitive impairment (HAND) using a machine learning approach from normal healthy controls. Methods: Twenty-seven HIV-infected patients and 14 healthy controls were enrolled in our study. Each set of BRAVO images was postprocessed using DPARSF3.1 to coregister all brains on the MNI template, and volume extraction of 90 brain regions was performed using custom-designed code. The machine learning method was performed using PRoNTo2.1.1 toolbox. The differences in brain volume between the HAND and non-HAND groups were analyzed. Results: GM volume effectively distinguished HIV-positive patients from healthy subjects with an AUC equals to 0.73. The sensitivity, specificity, and accuracy of the established classification were 85.19%, 42.86%, and 70.73%, respectively. GM volume value of the top ten brain regions was related to digit symbols, trail making test, digit span, vocabulary fluency, stroop C time, stroop CW time, CD4, and neuropsychological group. Conclusions: A machine learning approach facilitates early diagnosis of HAND in HIV patients by MRI-based GM volume measurement.

Effect of different epitaxial structures on GaAs photoemission.

The quantum efficiency equations of two different structure reflection-mode GaAs photocathodes with back interface recombination velocity have been solved from the diffusion equations. One structure consists of GaAs substrate and an epitaxial GaAs active layer (GaAs-GaAs) and another structure consists of GaAs substrate, an epitaxial AlGaAs buffer layer, and a GaAs active layer (AlGaAs-GaAs). The experimental results show that the quantum efficiency of long-wavelength photons and the integral sensitivities for GaAs-GaAs cathodes both increase with the increase in the active layer thickness, which is due to the increase of electron diffusion length. The quantum efficiency of long-wavelength photons and the integral sensitivity of AlGaAs-GaAs cathodes are greater than those of GaAs-GaAs cathodes with an identical active layer thickness, which is attributed to the AlGaAs buffer layer. The buffer layer can reflect electrons and improve the quality of the GaAs active layer. Through the theoretical simulation, we found the active layer thickness for AlGaAs-GaAs cathodes has an optimum value at which the cathodes achieve the maximum sensitivity.

[Biotransformation of daphnetin by suspension transgenic hairy roots of Polygonum multiflorum].

OBJECTIVE: To investigate the biotransformation of daphnetin by suspension transgenic hairy root of Polygonum multiflorum and provide a biotechnological method for large-scale production of the daphnetin-8-O-beta-D-glucoside using this new culture system. METHOD: Daphnetin was added into the media of suspension to culture 36 h. The biotransformation product was detected with TLC and HPLC, and isolated by various chromatographic methods. The influence of co-cultured time on conversion ratio, content of degradation product and the reason for the degradation of product II were investigated using HPLC. RESULT: One biotransformation product, daphnetin-8-O-beta-D-glucoside, was obtained, the optimal co-cultured time in suspension hairy root of P. multiflorum was 36 h with the highest biotransformation molar ratio of 32.11%, the sucrose medium (sucrose-only) can increase the biotransformation molar ratio to 72.44%. The result demonstrated that the degradation products of the product II was induced by the MS medium. CONCLUSION: The potential application of suspension transgenic hairy root of P. multflorum in the sucrose-only medium on generating daphnetin-8-Obeta-D- glucoside could be prospective.

[Biotransformation of 4-methyl-7-allyloxy coumarin by transgenic hairy roots of Polygonum multiflorum].

OBJECTIVE: To synthesis 4-methyl-7-allyloxy coumarin by Williamson etherification from 4-methyl-7-hydroxy coumarin and apply as a substrate in hairy roots of Polygonum multiflorum. METHODS: The synthesis reaction of 4-methyl-7-allyloxy coumarin used the allyl bromide and potassium carbonate as catalysts, and acetone as solvent reacted for 17 hours, then the product was isolated. 4-methyl-7-allyloxy coumarin was added into the media of supension transgenic hairy roots of Polygonum multiflorum which had been precultured for 8 d, and then co-cultured for another 7 d. The biotransformation products were detected by TLC and HPLC and isolated by various chromatographic methods. RESULTS: Two biotransformation products, 4-methyl-7-hydroxy coumarin and 4-methyl-coumarin-7-O-beta-D-glucoside were isolated and identified. CONCLUSION: Hairy roots of Polygonum multiflorum contains not only glycosyltransferase but also hydrolysis enzymes.

[Effect of FAM172A protein on apoptosis and proliferation in HEK293 cells].

OBJECTIVE: To study the effect of FAM172A protein related to diabetic macroangiopathy on apoptosis and proliferation in HEK293 cells. METHODS: The pDrive-FAM172A plasmid constructed in our previous study was used as a template to amplify human FAM172A open reading frame by a polymerase chain reaction. The resulting PCR products were subcloned into the eukaryotic expression vector PDC315 to construct recombinant PDC315-FAM172A plasmid. PDC315-FAM172A plasmid was identified by enzyme cleavage and sequencing analysis. HEK293 cells were transiently transfected respectively with appropriate PDC315 or PDC315-FAM172A plasmid by Lipofectamine 2000 according to the manufacturer's instruction. XTT assay and growth curve were used to observe the effect of over-expression of FAM172A gene on HEK293 cell proliferation. PI and Annexin V/PI staining method were used to assess the effect of FAM172A gene on apoptosis and cell cycle of HEK293 cell. RESULTS: Eukaryotic expression vector PDC315-FAM172A was successfully constructed and identified by enzyme cleavage and sequencing analysis. Compared with PDC315 plasmid transfection, the XTT assay showed that optical density (A) value increased by 52% when transfected with PDC315-FAM172A plasmid (0.21±0.07 vs 0.32±0.06, P<0.01). Growth curve revealed that HEK293 cells transfected with PDC315-FAM172A plasmid proliferated faster than those transfected with PDC315 plasmid. PI staining showed that, as compared with PDC315 plasmid transfection, the apoptotic rate of HEK293 cells transfected with PDC315-FAM172A plasmid decreased by 38.5% (23.79±1.36 vs 14.64±0.95, P<0.01), cell percentage of G0-G1 phases significantly decreased (66.79±1.73 vs 58.16±0.75, P<0.01) and cell percentage of S phases significantly increased (22.62±1.16 vs 33.56±0.94, P<0.01). Annexin V/PI staining revealed that, as compared with PDC315 plasmid transfection, the percentage of early and advanced apoptotic cells decreased by 28% (13.63±0.56 vs 9.79±0.39, P<0.01) and 29% (7.70±0.29 vs 5.43±0.29, P<0.01) respectively. CONCLUSION: FAM172A protein promotes cell proliferation, inhibits cell apoptosis and facilitates S-phases entry. It indicates that FAM172A protein is involved in cell growth regulation. Our findings provide a clue for further study on its physiological functions and roles in diabetic macroangiopathy.

Theoretical modeling and simulation-based assessment of graded-bandgap AlGaAs/GaAs electron-injection cathode.

The electron emission model of a negative electron affinity graded-bandgap AlGaAs/GaAs electron-injection cathode was developed from two-dimensional continuity equations. The emission current was obtained from a simulation of the model, and the emission current efficiency and emission current per unit length were calculated. Based on the simulation results and preparation conditions, the range of optimum parameters for the cathode structure were determined. The ranges of optimum thickness for the p-AlGaAs and the graded-bandgap p-AlGaAs layers were 0.05-0.15 µm and 0.1-0.3 µm, respectively. The optimum width of the base electrode ranged from 1 to 4 µm, and the optimum molar ratios of Al in the p-AlGaAs and the n-AlGaAs layers were 0.2-0.3 and 0.4-0.5, respectively. This abrupt PN heterojunction inhibited the hole current and increased the emission current efficiency, with a maximum value of 25.3%. According to the emission current per unit length, the optimum range of width of emission unit surface was 6 to 10 µm, and the peak emission current per unit length reached 43.2 µA/µm.

Association between polymorphisms in the interleukin-10 gene and susceptibility to human immunodeficiency virus-1 infection: A systematic review and meta-analysis.

BACKGROUND: This study meta-analyzed the literature on possible association of 3 polymorphisms (-592, -1082, -819) in the interleukin-10 (IL-10) gene with susceptibility to human immunodeficiency virus (HIV)-1 infection. METHODS: PubMed, EMBASE, MEDLINE and Google Scholar were systematically searched to identify relevant studies in English. Meta-analyses were performed to examine the association of IL-10 polymorphisms -592, -1082, and -819 with susceptibility to HIV-1 infection. RESULTS: A significant association between the -592 polymorphism and susceptibility to HIV-1 infection was found in the total population (recessive model, odds ratios (OR) = 1.44, 95% CI = 1.06-1.96, P = .02; homozygous model, OR = 1.44, 95% CI = 1.02-2.02, P = .04). However, these results were not observed in subgroups based on ethnicity. The -1082 polymorphism was significantly associated with susceptibility to HIV-1 infection in Caucasians (OR = 1.30, 95% CI = 1.05-1.62, P = .02; recessive model, OR = 1.49, 95% CI = 1.09-2.03, P = .01; homozygous model, OR = 1.58, 95% CI = 1.01-2.46, P = .04), but not in Asians or the total population. None of the 5 genetic models suggested a significant association between the -819 polymorphism and HIV-1 infection. CONCLUSION: The available evidence indicates that the AA genotype of IL-10 -592 may confer increased susceptibility to HIV-1 infection, and that the AA genotype of -1082 may confer increased susceptibility in Caucasians. In contrast, the -819 polymorphism may not be associated with HIV-1 infection risk. These conclusions should be verified in large, well-designed studies.