Prevalence and risk factors of low birth weight in the United States: An analysis of 2016-2021 data.

BACKGROUND: Low birthweight (LBW), infants weighing less than 2,500 g, is a global health concern associated with high infant morbidity and mortality rates. This study investigates LBW prevalence and its relation to maternal sociodemographic characteristics and lifestyle behaviors factors in the United States (US). METHODS: This analysis used the National Survey of Children's Health (NSCH) data from 2016 to 2021, including n = 225,443 children aged 0-17 years. 18,131 had LBW (<2,500 g), and 2810 had very LBW (VLBW) (<1,500 g). Logistic regression calculated odds ratios (OR) using LBW as the dependent variable, adjusting for various factors. RESULTS: Between 2016 and 2021 in the United States, LBW prevalence averaged 9.31%, with VLBW at 1.50%. Mothers aged 18-35, White, had the lowest LBW (7.63%) and VLBW (1.17%) rates. Mothers aged ≤18 years, black, had the highest LBW (15.45%) and VLBW infants (4.70%). Maternal age emerged as a significant LBW factor, with an OR of 1.27 for ≤18 and 1.19 for >35. Children in poor health had the highest OR (2.87). Race/ethnicity and other disparities were observed. CONCLUSION: Our study highlights LBW risk among non-White mothers with specific criteria, emphasizing the need for continued exploration of intersectional targets for change that are exacerbating LBW disparities among marginalized populations which may be artificially attributed to biologic determinants and individual-level risk factors. In-depth analysis of repressive structures at the root of inequalities demand continued research on macro levels of influence. Customized healthcare reform holds the greatest potential to disrupt the patterns contributing to poor health outcomes among LBW children, and will ultimately maximize the reach and effectiveness of health promotion strategies and clinical practices aimed to improve universal maternal and infant health.

Factors Influencing Vision Health and Eye Care among Older Adults in Northeast Tennessee.

OBJECTIVES: The purpose of this study was to examine the factors associated with vision impairment (VI), age-related eye disease (ARED), and frequency of eye examinations among older adults. METHODS: A cross-sectional study (N = 166) was designed to identify barriers in vision and eye care services among adults 50 years and older in four counties in Appalachian Tennessee. Surveys were administered in March 2023. Simple and multiple logistic regression analyses were used to determine the risk factors of VI and ARED and the frequency of eye examinations. RESULTS: In two out of the three regression models, predictors such as traveling >10 mi to an eye care provider, barriers to eye care, and a lack of exposure to eye health information emerged as significant factors. Individuals who traveled >10 mi to an eye care provider were more than twice as likely than individuals who traveled shorter distances to have VI and not maintain routine eye care (adjusted odds ratio [AOR] 2.69, 95% confidence interval [CI] 1.08-6.75; AOR 2.82, 95% CI 1.05-7.55, respectively). Reporting barriers to eye care doubled the odds of ARED (AOR 2.33, 95% CI 1.02-5.34) and substantially increased the odds of reporting a 3-year or longer interval since the last eye examination (AOR 7.45, 95% CI 1.85-29.96) compared with having no barriers to eye care. Moreover, limited exposure to eye health information tripled the odds of VI (AOR 3.26, 95% CI 1.15-9.24) and not maintaining routine eye care (AOR 3.07, 95% CI 0.97-9.70) compared with more exposure to eye health information. Other predictors also were uncovered in the analysis. CONCLUSIONS: This study contributes to the scarce literature on risk factors associated with vision health among older adults in Appalachia.

The Impact of Providing Free HIV Self-testing on Sexual Risk Behaviors Among Men who have Sex with Men in Hunan, China: A Randomized Controlled Trial.

HIV self-testing (HIVST) increases testing frequency among men who have sex with men (MSM). However, its impact on sexual risk behaviors is unclear. In a randomized controlled trial conducted in Hunan Province, China, HIV-negative MSM were randomized to receive one of two interventions for one year: (1) facility-based HIV testing, or (2) facility-based HIV testing augmented with free HIVST. From April to June 2018, 230 MSM were enrolled. They self-reported sexual behaviors every 3 months for 12 months. Among 216 MSM with follow-ups (intervention: 110; control: 106), adjusting for potential confounders in Generalized Estimating Equation models, there were no statistically significant differences in consistent condom use with male partners (regular/casual) or female partners, nor on number of male or female sexual partners. Provision of free HIVST kits does not increase risky sex and should be included in comprehensive HIV prevention packages, particularly for sexual minority men in China.

Prevalence of HIV testing and factors influencing the attitude of high school students towards HIV testing uptake in U.S. using, Youth Risk Behavior Survey 2017 data.

This study examined associations between the prevalence of HIV testing and factors or behaviors that influence HIV testing in U.S.A. 9th to 12th graders using the 2017 Youth Risk Behavior Surveillance Survey (YRBSS) data. Selection criteria was based on a positive report of sexual debut (Ever had sex? Yes/No). Outcome of interest was having ever tested for HIV. Independent risk factors included age, sex, grade, race, condom use, age at first sexual intercourse, number of lifetime sexual partners, use of contraceptives, use of drug or alcohol before last sexual activity and several other factors. Chi-square and logistic regression analyses were conducted to evaluate factors associated with HIV screening participation. HIV testing prevalence was 20.34%. Females (53.97%) were more likely to participate in HIV screening test than males (67.37% females versus 32.63% males) and had higher odds of testing (OR: 2.229; p < .0001). Those in 11th and 12th grade, aged greater than 16 and with multiple sexual partners had higher rates of HIV testing. Strongest associations with HIV testing were older age at 1st sexual intercourse, odds ratio (OR): 0.413; (p ≤ .0001), having three or more sexual partners (OR: 2.023; p ≤ .0001), being female (OR: 2.021; p ≤ .0001), use of contraceptives (OR: 1.828; p ≤ .0001) and describing grades in school as mostly A's or B's (OR: 0.696; p ≤ .001).

Association between per and polyfluoroalkyl substances and markers of inflammation and oxidative stress.

OBJECTIVES: This study aimed to examine the association of Per and Polyfluoroalkyl substances (PFAS) and markers of chronic inflammation and oxidative stress. METHODS: Using data (n = 6652) from the National Health and Nutrition Examination Survey (NHANES) 2005-2012, generalized linear models were used to examine the association between PFAS and inflammatory (ferritin, alkaline phosphatase, C-reactive protein, absolute neutrophil count and lymphocyte count) and oxidative stress (serum bilirubin, albumin and iron) per unit exposure to PFAS while adjusting for covariates. Study participants were those ≥20 years of age. Outcome variables were markers of chronic inflammation and oxidative stress and exposure variables were PFAS. RESULLTS: Percentage change in Perfluorohexane sulfonic acid (PFHxS), Perfluorononanoic acid (PFNA), Perfluorooctanoic acid (PFOA), Perfluorooctane sulfonic acid (PFOS), and Perfluorodecanoic acid (PFDA) were all significantly associated with percentage increases in lymphocyte counts, beta (95% confidence interval); 0.04(0.02,0.05), 0.04(0.02,0.05), 0.05(0.03, 0.07), 0.04(0.03,0.05), 0.03(0.13,1.23) and with percentage increases in serum iron 0.07(0.05,0.09), 0.04(0.02,0.07), 0.10(0.07,0.12), 0.05(0.03,0.07), 0.04(0.02,0.06) and increased serum albumin 0.02(0.02,0.02), 0.02(0.02,0.03), 0.03(0.03,0.04), 0.02(0.017, 0.025), 0.01 (0.01, 0.05). Only PFHxS, PFNA, PFOA and PFOS were associated with percentage increases in serum total bilirubin 0.04(0.03,0.05), 0.02(0.00,0.03), 0.06(0.04,0.08), 0.03(0.02,0.05). Similar results were obtained for categorical quintile analysis with PFOA showing a significant trend (P < 0.001) with lymphocyte count, serum iron, serum total bilirubin and serum albumin. Trend for neutrophil count was not significant (p = 0.183). CONCLUSION: Per and Polyfluoroalkyl substances are associated with markers of chronic inflammation and oxidative stress. Increased exposure leads to increase in serum concentration of these markers meaning these chemicals are associated with both chronic inflammation and oxidative stress.

Proxy reliability of the 12-item world health organization disability assessment schedule II among adult patients with mental disorders.

PURPOSE: Despite the wide usage of World Health Organization Disability Assessment Schedule II (WHODAS 2.0) in psychiatry research and clinical practice, there was limited knowledge on its proxy reliability among people with mental disorders. This paper aimed to compare the 12-item WHODAS 2.0 responses of adult patients with mental disorders to their family caregivers. METHODS: In this study, 205 pairs of patients with mental disorders and primary family caregivers were consecutively recruited from one inpatient mental health department in a large hospital in China. All participants completed the 12-item version WHODAS 2.0 to assess patients' functioning in the 30 days prior to the hospitalization. Measurement invariance, including configural, metric and scalar invariance, was tested across patient and proxy groups, using multi-group confirmatory factor analysis. Agreement between patients and proxies was examined by paired Wilcoxon tests and intraclass correlation coefficients (ICC). Subgroup analyses for proxy reliability were conducted within strata of proxy kinship and patient psychiatric diagnosis. RESULTS: The 12-item WHODAS 2.0 achieved configural, metric and partial scalar invariance across patient and proxy groups. Unsatisfactory consistency was found for most items (ICC < 0.75, P < 0.05), especially for items on Cognition, Getting along, Life activities, and Participation in society (ICC < 0.4, P < 0.05). Spouses agreed with patients more often than parents (ICC ≥ 0.4, P < 0.05). The paired Wilcoxon tests found that impairment of patients with psychotic disorders tended to be overestimated by proxies while proxies tended to underestimate impairment of patients with mood disorders. CONCLUSION: Our study reveals inconsistency between self and proxy reports in the 12-item WHODAS 2.0 among adult patients with mental disorders. When proxy reports is needed, spouses are preferred than parents. We should be aware of proxies' impairment overestimation among patients with psychotic disorders and underestimation among patients with mood disorders.

Changes in oxidation-antioxidation function on the thymus of chickens infected with reticuloendotheliosis virus.

BACKGROUND: Reticuloendotheliosis virus (REV) is a retrovirus that causes severe immunosuppression in poultry. Animals grow slowly under conditions of oxidative stress. In addition, long-term oxidative stress can impair immune function, as well as accelerate aging and death. This study aimed to elucidate the pathogenesis of REV from the perspective of changes in oxidative-antioxidative function following REV infection. METHODS: A total of 80 one-day-old specific pathogen free (SPF) chickens were randomly divided into a control group (Group C) and an REV-infected group (Group I). The chickens in Group I received intraperitoneal injections of REV with 104.62/0.1 mL TCID50. Thymus was collected on day 1, 3, 7, 14, 21, 28, 35, and 49 for histopathology and assessed the status of oxidative stress. RESULTS: In chickens infected with REV, the levels of H2O2 and MDA in the thymus increased, the levels of TAC, SOD, CAT, and GPx1 decreased, and there was a reduction in CAT and Gpx1 mRNA expression compared with the control group. The thymus index was also significantly reduced. Morphological analysis showed that REV infection caused an increase in the thymic reticular endothelial cells, inflammatory cell infiltration, mitochondrial swelling, and nuclear damage. CONCLUSIONS: These results indicate that an increase in oxidative stress enhanced lipid peroxidation, markedly decreased antioxidant function, caused thymus atrophy, and immunosuppression in REV-infected chickens.

Association between stigma towards HIV and MSM and intimate partner violence among newly HIV-diagnosed Chinese men who have sex with men.

BACKGROUND: HIV- and MSM-related stigma are well documented as common for Chinese men who have sex with men (MSM) living with HIV, yet there is sparse literature on intimate partner violence (IPV) and its relationship with stigma in this vulnerable population. To evaluate the association between HIV-stigma and stigma related to homosexuality and IPV among newly HIV-diagnosed MSM in China. METHODS: Data were collected in the baseline survey among newly HIV-diagnosed Chinese MSM in a randomized clinical trial via face-to-face interviews. Univariate logistic and multivariate logistic regression analyses were performed to assess the associations between IPV and HIV- and MSM-related stigma. RESULTS: Of 367 newly HIV-diagnosed Chinese MSM, 23.7% experienced any IPV, including 16.6% physical, 7.4% psychological and 5.2% sexual IPV. Positive associations were found between HIV- and MSM-related stigma and IPV. Men with high HIV-related stigma (score ≥ 27) were 1.67 times as likely to experience any IPV as those with low stigma (adjusted odds ratio [AOR]: 1.67, 95% confidence interval [CI]: 1.02-2.76). Men with high MSM-related stigma (score ≥ 6) were 1.99 times as likely to experience any IPV as those with low stigma (AOR: 1.99, 95% CI: 1.18-3.36). CONCLUSIONS: HIV- and MSM-related stigmas was positively associated with IPV experiences among newly diagnosed MSM in China. The manner in which stigma may exacerbate IPV, and/or the influence of IPV on worsening stigma should be further evaluated. The high prevalence of IPV and stigma in this population suggests that interventions should be taken to reduce stigma and prevent this risky behavior among MSM.

Negative associations between general self-efficacy and anxiety/depression among newly HIV-diagnosed men who have sex with men in Beijing, China.

To evaluate the association between general self-efficacy and depression/anxiety among newly HIV-diagnosed Chinese men who have sex with men (MSM) in Beijing, our study evaluated the baseline survey data of MSM taking part in a clinical trial among Chinese MSM in Beijing. The baseline survey of the trial was conducted between March 2013 and March 2014. General self-efficacy and depression/anxiety were measured using standard scales. Logistic regression and cumulative logistic regression were used to evaluate the associations between general self-efficacy and depression/anxiety. A total of 367 newly HIV-diagnosed Chinese MSM in Beijing were recruited. There were negative associations between general self-efficacy and depression/anxiety among the study population. As general self-efficacy increased by one unit, the odds of "likely" or "borderline" depression versus normal, or "likely" depression versus "borderline" depression or normal decreased by 12% [adjusted odds ratio (AOR): 0.88, 95% confidence interval (CI): 0.85-0.92] after adjusting for potential confounders. Similarly, general self-efficacy was negatively associated with anxiety (AOR: 0.89, 95% CI: 0.86-0.93). A higher level of general self-efficacy was associated with lower levels of depression and anxiety among newly HIV-diagnosed Chinese MSM. Interventions promoting overall health and wellness should address self-efficacy, depression and anxiety.

Inhibition of tumor necrosis factor alpha and increased of interleukin 10 by Lactobacillus: a molecular mechanism protection against TNBS-induced ulcerative colitis in chicks.

The purpose of this study was to evaluate the effects and mechanism of Lactobacillus on ameliorating ulcerative colitis chicks induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). There are three groups in this study, control, Lactobacillus and ulcerative colitis groups. 1-day-old chicks were fed with microcapsules containing Lactobacillus LA-5 daily for Lactobacillus group and clustered with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to make the model of ulcerative colitis at ten-day-old. Chicks in control and ulcerative colitis groups were fed with empty microcapsules daily at 1-day-old and then chicks in ulcerative colitis group were induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) for preparation of ulcerative colitis model at 10-day-old. We detected the changes of mRNA and protein expression of TNF-α and IL-10 in the colon by Real-Time PCR and Western Blot. Histopathology evaluation on colon was conducted. Results showed that chicks pretreated with Lactobacillus had striking injury improvement compared with ulcerative colitis group in histopathology. Compared with ulcerative colitis group, down-regulation of TNF-α and up-regulation of IL-10 were observed in Lactobacillus group chicks. Therefore, Lactobacillus could improve the injury of intestinal mucosa and reduce inflammatory response by regulating mRNA and protein expression levels of TNF-α and IL-10, respectively. In conclusion, Lactobacillus could ameliorate the effects on chicks of TNBS-induced ulcerative colitis by reducing the inflammation and regulating the expression of TNF-α and IL-10, respectively.

Comparison of immune responses induced by porcine parvovirus virus-like particles and inactivated vaccine.

Laboratory-prepared inactivated porcine parvovirus (PPV) vaccines and VP2 virus-like particles (VLPs) were utilized to immunize gilts. PPV BQ strain and SP2/0 cells were used. Hemagglutination-inhibiting (HI) antibody titers were measured in the immunized gilts and the differences in cytokine production of interferon gamma (IFN-γ, IL-2 and IL-4) were compared. CD4+ and CD8+ T cells proliferation were compared by flow cytometry. The variation between the immune response level induced by inactivated PPV vaccine and VP2 VLPs were determined. The results showed that all vaccinated gilts had HI antibody titers reaching 1:256 for at least one month post immunization and the peak level of antibody could be sustained for one month; further, PPV antibodies could be detected in the second week post immunization with VP2 VLPs. We also found that the level of cytokines (IFN-γ, IL-2 and IL-4) were all increased post immunization and continued to rise after the booster immunization; the level of increase in IFN-γ and IL-2 were significantly higher than IL-4. The flow cytometry results showed that the numbers of the CD4+ and CD8+ T cells subsets were significantly higher in the groups immunized with inactivated PPV vaccine or VP2 VLPs than those of negative control group (p<0.01); additionally, the number of CD4+ cells in the gilts that received VP2 VLP immunization was significantly higher than the inactivated vaccine group (p<0.01). In summary, the inactivated PPV vaccine and PPV VP2 VLPs were both able to induce humoral and cellular immunity, but the VP2 VLPs lead to better cellular immune responses in gilts compared to those of the inactivated vaccine..

Mechanistic understanding of N-glycosylation in Ebola virus glycoprotein maturation and function.

The Ebola virus (EBOV) trimeric envelope glycoprotein (GP) precursors are cleaved into the receptor-binding GP1 and the fusion-mediating GP2 subunits and incorporated into virions to initiate infection. GP1 and GP2 form heterodimers that have 15 or two N-glycosylation sites (NGSs), respectively. Here we investigated the mechanism of how N-glycosylation contributes to GP expression, maturation, and function. As reported before, we found that, although GP1 NGSs are not critical, the two GP2 NGSs, Asn563 and Asn618, are essential for GP function. Further analysis uncovered that Asn563 and Asn618 regulate GP processing, demannosylation, oligomerization, and conformation. Consequently, these two NGSs are required for GP incorporation into EBOV-like particles and HIV type 1 (HIV-1) pseudovirions and determine viral transduction efficiency. Using CRISPR/Cas9 technology, we knocked out the two classical endoplasmic reticulum chaperones calnexin (CNX) and/or calreticulin (CRT) and found that both CNX and CRT increase GP expression. Nevertheless, NGSs are not required for the GP interaction with CNX or CRT. Together, we conclude that, although Asn563 and Asn618 are not required for EBOV GP expression, they synergistically regulate its maturation, which determines its functionality.

Analysis of alternative splicing in chicken embryo fibroblasts in response to reticuloendotheliosis virus infection.

Alternative splicing (AS) plays a significant role in regulation of genomic expression at the transcriptional level and is involved in many important biological functions of cells, thus a gene can be spliced into distinct transcript variants then translated to many different kinds of protein. Reticuloendotheliosis virus (REV) is a kind of retrovirus that can infect multiple avian species, leading to runting syndrome, immunosuppression and oncogenesis. In this present study, we analyzed AS in REV-infected chicken embryo fibroblasts (CEFs) which were inoculated with the second generation of REV (group VB) and compared with normal CEFs (group C) by high-throughput RNA sequencing technology. A total of 6,939 genes which were alternatively spliced were detected, among them, skipped exon (SE) was the most common pattern. Moreover, 5,607 AS genes were detected as differentially expressed; compared with group C, group VB has 2,825 genes upregulated significantly and 2,782 genes downregulated significantly. These 5,607 differentially expressed AS genes are involved in many important biological processes. Many of them are involved in apoptosis and tumourigenesis. We also proved, by agarose gel electrophoresis, that AS events predicted by our study are authentic and AS is closely related with apoptosis and tumourigenesis in REV-infected CEFs. Our study provides the best analysis to date of the potential link between AS and CEFs in response to REV infection. Research highlights Transcriptomics analysis of REV-infected CEFs using high-throughput sequencing. Potential link between alternative splicing and CEFs in response to REV infection. Skipped exon is the most common spliced pattern in REV-infected CEFs. Differentially expressed genes mainly involved in apoptosis and tumourigenesis.

Analysis of microRNA expression profile in specific pathogen-free chickens in response to reticuloendotheliosis virus infection.

Reticuloendotheliosis virus (REV) is an avian retrovirus that causes immunosuppression, growth retardation, and oncogenesis in a variety of birds. REV infection is epidemic in many countries. In this study, we used high-throughput sequencing to identify microRNAs (miRNAs) associated with REV infection. A total of 88 differentially expressed miRNAs were identified in samples collected on days 21 and 28 post-REV infection. Possible target genes of the differentially expressed miRNAs were analyzed. We observed that expression of proapoptotic, proto-oncogene, and carcinogenic cytokine mRNAs was highly upregulated, whereas expression of antiapoptotic cytokine mRNAs was significantly downregulated. Our findings provide a potential link between miRNA expression and the pathogenesis of REV infection.

Prevalence of and Trends in Diabetes Among Veterans, United States, 2005-2014.

Diabetes is a highly prevalent chronic disease among US adults, and its prevalence among US veterans is even higher. This study aimed to examine the prevalence of and trends in diabetes in US veterans by using data from the US National Health and Nutrition Examination Survey from 2005 through 2014. The overall prevalence of diabetes and undiagnosed diabetes was 20.5% and 3.4%, respectively, and increased from 15.5% in 2005-2006 to 20.5% in 2013-2014 (P = .04). Effective prevention and intervention approaches are needed to lower diabetes prevalence among US veterans and ultimately improve their health status.

60S ribosomal protein L35 regulates ß-casein translational elongation and secretion in bovine mammary epithelial cells.

60S ribosomal protein L35 (RPL35) is an important component of the 60S ribosomal subunit and has a role in protein translation and endoplasmic reticulum (ER) docking. However, few studies have investigated RPL35 in eukaryotes and much remains to be learned. Here, we analyzed the function of RPL35 in ß-casein (CSN2) synthesis and secretion in bovine mammary epithelial cells (BMECs). We found that methionine (Met) could promote the expressions of CSN2 and RPL35. Analysis of overexpression and inhibition of RPL35 confirmed that it could mediate the Met signal and regulate CSN2 expression. The mechanism of CSN2 regulation by RPL35 was analyzed by coimmunoprecipitation (Co-IP), colocalization, fluorescence resonance energy transfer (FRET) and gene mutation. We found that RPL35 could control ribosome translational elongation during synthesis of CSN2 by interacting with eukaryotic translational elongation factor 2 (eEF2), and that eEF2 was the signaling molecule downstream of RPL35 controlling this process. RPL35 could also control the secretion of CSN2 by locating it to the ER. Taken together, these results revealed that, RPL35 was an important positive regulatory factor involving in the Met-mediated regulation of CSN2 translational elongation and secretion.

Development of a real-time reverse transcription loop-mediated isothermal amplification method for the rapid detection of porcine epidemic diarrhea virus.

BACKGROUND: Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease characterized by severe enteritis, vomiting and watery diarrhea in swine. Recently, the outbreak of the epidemic disease has been a serious problem in swine industry. The objective of this study is to develop a rapid, sensitive, and real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for the detection of porcine epidemic diarrhea virus (PEDV) in less equipped laboratories. RESULTS: The optimal reaction condition of the current real-time RT-LAMP for PEDV was 62 °C for 45 min. It was capable of detecting PEDV from clinical samples and differentiating PEDV from several related porcine viruses, while it did not require additional expensive equipment. The minimum detection limit of the real-time RT-LAMP assay was 0.07PFU per reaction for PEDV RNA, making this assay approximately 100-fold more sensitive than that of one-step RT-PCR. By screening a panel of clinical specimens, the results showed that this method presented a similar sensitivity with real-time RT-PCR and was somewhat sensitive than one-step RT-PCR in detection of clinical samples. CONCLUSIONS: In this study, we have developed a new real-time RT-LAMP method, which is rapid, sensitive and efficient to detect PEDV.This method holds great promises not only in laboratory detection and discrimination of PEDV but also in large scale field and clinical studies.

Opsonization Inveigles Macrophages Engulfing Carrier-Free Bilirubin/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy.

Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease-modifying treatments for OA are currently lacking. Because inflammation mediated by an imbalance of M1/M2 macrophages in the synovial cavities contributes to OA progression, regulating the M1 to M2 polarization of macrophages can be a potential therapeutic strategy. Basing on the inherent immune mechanism and pathological environment of OA, an immunoglobulin G-conjugated bilirubin/JPH203 self-assembled nanoparticle (IgG/BRJ) is developed, and its therapeutic potential for OA is evaluated. After intra-articular administration, IgG conjugation facilitates the recognition and engulfment of nanoparticles by the M1 macrophages. The internalized nanoparticles disassemble in response to the increased oxidative stress, and the released bilirubin (BR) and JPH203 scavenge reactive oxygen species (ROS), inhibit the nuclear factor kappa-B pathway, and suppress the activated mammalian target of rapamycin pathway, result in the repolarization of macrophages and enhance M2/M1 ratios. Suppression of the inflammatory environment by IgG/BRJ promotes cartilage protection and repair in an OA rat model, thereby improving therapeutic outcomes. This strategy of opsonization involving M1 macrophages to engulf carrier-free BR/JPH203 nanoparticles to suppress inflammation for OA therapy holds great potential for OA intervention and treatment.

Neddylation pathway regulates the proliferation and survival of macrophages.

Neddylation is a new type of protein post-translational modification which adds the ubiquitin-like molecule Nedd8 to target proteins. The well-identified targets of neddylation are cullins, which serve as essential components of Cullin-RING E3 ligases (CRL). It is reported that inhibition of neddylation repressed NF-κB-mediated proinflammatory cytokine production in macrophages. However, the role of neddylation in the proliferation and survival of macrophages has not been well defined. Here we report that partial inactivation of the neddylation pathway by a specific Nedd8-activating enzyme E1 (NAE) inhibitor MLN4924 reduced LPS-induced production of the proinflammatory cytokines TNF-α and IL-6 without obvious impairment of cell viability. However, persistent and severe inactivation of neddylation by MLN4924 significantly inhibited cell proliferation by inducing G2 phase cell-cycle arrest and further triggered cell death by inducing apoptosis in RAW264.7 macrophages. Mechanistic analysis revealed that inactivation of neddylation blocked cullin neddylation, inhibited CRL E3 ligase activity, and thus led to the accumulation of CRL substrates, resulting in cell-cycle arrest, DNA damage response and apoptosis. The findings revealed that neddylation serves as an important signaling pathway regulating the proliferation and survival of macrophages.

Maternal depressive symptoms and the risk of overweight in their children.

To examine the association between maternal depressive symptoms during early childhood of their offspring and later overweight in the children. Only children (n = 1,090) whose weights and heights were measured at least once for three time points (grades one, three and six) from the National Institute of Child Health and Human Development Study were included. Maternal depressive symptoms, defined as a Center for Epidemiologic Studies Depression Scale (CES-D) score of 16 or greater, were assessed using CES-D when the child was 1, 24, and 36 months. Childhood overweight was based on standardized height and weight measures taken during the interviews, and was defined according to appropriate CDC age- and sex-specific BMI percentiles. Generalized estimating equation was used to examine the impact of maternal depressive symptoms on the childhood overweight after adjusting for covariates. Compared to children of mothers without depression at any of the three time points, when children were one, 24 and 36 months of age, children of mothers with depression at all three time points were 1.695 times more likely to be overweight after adjusting for other child characteristics (95 % CI = 1.001-2.869). When further adjusted for maternal characteristics, children of mothers with depression at all three time points were 2.13 times more likely to be overweight (95 % CI = 1.05-4.31). Persistent maternal depressive symptoms may be associated with an increased risk of childhood overweight in their offspring. Children of mothers with depression may benefit from special attention in terms of obesity prevention.