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Background: Hashimoto's thyroiditis (HT) is a thyroid autoimmune disease characterized by lymphocytic infiltration and thyroid destruction. Prunella vulgaris (PV) is a traditional Chinese herbal medicine with documented clinical efficacy in treating HT. We previously reported an immunoregulatory effect of PV in thyrocytes; however, the bioactive components of PV remained unclear. This study aimed to elucidate key components of PV for treating HT and their acting mechanisms. Methods: Network pharmacology was used to predict key PV components for HT. The predicted components were tested to determine whether they could exert an immunoregulatory effect of PV in human thyrocytes. Limited proteolysis-mass spectrometry (Lip-MS) was used to explore interacting proteins with PV components in human thyrocytes. Microscale thermophoresis binding assay was used to evaluate the affinity of PV components with the target protein. Results: Eleven PV components with 192 component targets and 3415 HT-related genes were gathered from public databases. With network pharmacology, a ‘component-target-disease’ network was established wherein four flavonoids including quercetin, luteolin, kaempferol, morin, and a phytosterol, β-sitosterol were predicted as key components in PV for HT. In stimulated primary human thyrocytes or Nthy-ori-31 cells, key components inhibited gene expressions of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interferon-β (IFN-β), cellular apoptosis, and activation of nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3). Heat shock protein 90 alpha, class A, member 1 (HSP90AA1), was identified to interact with flavonoids in PV by Lip-MS. Morin had the highest affinity with HSP90AA1 (KD = 122.74 μM), followed by kaempferol (KD = 168.53 μM), luteolin (KD = 293.94 μM), and quercetin (KD = 356.86 μM). Conclusion: Quercetin, luteolin, kaempferol, morin, and β-sitosterol reproduced an anti-inflammatory and anti-apoptosis effect of PV in stimulated human thyrocytes, which potentially contributed to the treatment efficacy of PV in HT.

IntroductionWe aimed to comprehensively investigate the causal relationship between 731 immune cell traits and autoimmune thyroiditis (AIT) and to identify and quantify the role of 1400 metabolic traits as potential mediators in between.MethodsUsing summary-level data from genome-wide association studies (GWAS) we performed a two-sample bidirectional Mendelian randomization (MR) analysis of genetically predicted AIT and 731 immune cell traits. Furthermore, we used a two-step MR analysis to quantify the proportion of the total effects (that the immune cells exerted on the risk of AIT) mediated by potential metabolites.ResultsWe identified 24 immune cell traits (with odds ratio (OR) ranging from 1.3166 6 to 0.6323) and 10 metabolic traits (with OR ranging from 1.7954 to 0.6158) to be causally associated with AIT, respectively. Five immune cell traits (including CD38 on IgD+ CD24-, CD28 on CD28+ CD45RA+ CD8br, HLA DR+ CD4+ AC, TD CD4+ %CD4+, and CD8 on EM CD8br) were found to be associated with the risk of AIT, which were partially mediated by metabolites (including glycolithocholate sulfate, 5alpha-androstan-3alpha,17beta-diol disulfate, arachidonoylcholine, X-15486, and kynurenine). The proportion of genetically predicted AIT mediated by the identified metabolites could range from 5.58% to 17.7%.DiscussionOur study identified causal associations between AIT and immune cells which were partially mediated by metabolites, thus providing guidance for future clinical and basic research.

Background: Mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) can occur intrauterine, intrapartum, and postpartum. Currently, infants with confirmed positive results in virological tests before 48 h of age are defined as having intrauterine infection. Aim: We herein review the literature that identifies emerging challenges in diagnosing intrauterine HIV infection to rethink the current diagnostic criteria. Findings: A number of reports have shown that some infants who were diagnosed with intrauterine HIV infection after birth became negative for HIV in the subsequent follow-ups, including negative HIV antibodies at the age of 12–18 months. Such ''clearance'' of HIV was attributed to various reasons: neonatal antiretroviral treatment (ART), false positivity, strong host immune response, or unknown factors in maternal breast milk. Discussions: Positive HIV tests in newborn infants shortly after birth do not necessarily indicate HIV infection, because maternal HIV can enter fetal circulation intrapartum due to the repetitive, strong uterine contractions. The infants are therefore exposed to, but may not yet be infected with HIV at that time. The current diagnostic criteria cannot differentiate HIV exposure from HIV infection, leading to so-called “challenges in diagnosing intrauterine HIV infection”. Those infants diagnosed with intrauterine infection who cleared HIV later were less likely to have been truly infected with HIV, but more likely to have been exposed to HIV. Moreover, we suggest that the determination of HIV antibody titers in infants’ serial serum samples can provide valuable information to distinguish intrapartum exposure from intrauterine infection.

Abstract Background Previous research has shown an association between homebound status and falls among older adults. However, this association was primarily drawn from cross-sectional studies. This study aimed to determine the bidirectional relationship between homebound status and falls among older adults in the community. Methods We used data of the community-dwelling older adults from 2011 to 2015 of the National Health and Aging Trends Study, a nationally representative survey of Medicare Beneficiaries in the United States (Sample 1 [No falls at baseline]: N = 2,512; Sample 2 [Non-homebound at baseline]: N = 2,916). Homebound status was determined by the frequency, difficulty, and needing help for outdoor mobility. Falls were ascertained by asking participants whether they had a fall in the last year. Generalized estimation equation models were used to examine the bidirectional association between homebound status and falls longitudinally. Results Participants with no falls at baseline (n = 2,512) were on average, 76.8 years old, non-Hispanic whites (70.1%), and female (57.1%). After adjusting for demographics and health-related variables, prior year homebound status significantly contributed to falls in the following year (Odds ratio [OR], 1.28, 95% CI: 1.09–1.51). Participants who were non-homebound at baseline (n = 2,916) were on average, 75.7 years old, non-Hispanic white (74.8%), and female (55.8%). Previous falls significantly predicted later homebound status (OR, 1.26, 95% CI: 1.10–1.45) in the full adjusted model. Conclusion This is the first longitudinal study to determine the bidirectional association between homebound status and falls. Homebound status and falls form a vicious circle and mutually reinforce each other over time. Our findings suggest the importance of developing programs and community activities that reduce falls and improve homebound status among older adults.

Abstract Background Anxiety and depressive symptoms are associated with fear of falling and fear of falling-related activity restrictions. However, it remains unknown whether anxiety or depressive symptoms alone could predict fear of falling and activity restrictions in older adults. We sought to determine if anxiety and depressive symptoms alone could be an independent predictor of fear of falling and activity restrictions in community-dwelling older adults. Methods This longitudinal analysis used waves 5 (time 1, [T1]) and 6 (time 2, [T2], 1 year from T1) data (N = 6376) from the National Health and Aging Trends Study. The Generalized Anxiety Disorder Scale 2 and Patient Health Questionnaire 2 were used to assess anxiety and depressive symptoms, respectively. Interview questions included demographics, health-related data, and fall worry levels (no fear of falling, fear of falling but no activity restrictions, and activity restrictions). Using multinomial logistic regression models, we examined whether anxiety and depressive symptoms (T1) predicted fear of falling and activity restrictions (T2). Results In wave 5 (T1, mean age: 78 years, 58.1% female), 10 and 13% of participants reported anxiety and depressive symptoms. About 19% of participants experienced fear of falling but not activity restrictions, and 10% of participants developed activity restrictions in wave 6 (T2), respectively. Participants with anxiety symptoms at T1 had a 1.33 times higher risk of fear of falling (95% CI = 1.02–1.72) and 1.41 times higher risk of activity restrictions (95% CI = 1.04–1.90) at T2. However, having depressive symptoms did not show any significance after adjusting for anxiety symptoms. Conclusions Anxiety symptoms seemed to be an independent risk factor for future fear of falling and activity restrictions, while depressive symptoms were not. To prevent future fear of falling and activity restrictions, we should pay special attention to older individuals with anxiety symptoms.

Postvaccination serologic testing (PVST) is utilized to monitor the success or failure of vaccination against hepatitis B virus (HBV) infection in infants of hepatitis B surface antigen (HBsAg) positive mothers. This secondary analysis of 1255 infants of HBsAg-positive mothers at 7–14 months age included in two prospective studies aimed to determine the optimal interval for PVST after three hepatitis B vaccine doses. HBsAg and anti-HBs were quantitatively tested with microparticle enzyme immunoassay. The average PVST interval was 3.8 ± 2.2 months. Overall, 1.7% (21/1255) infants had anti-HBs

Before the availability of COVID-19 vaccines, surveys showed that vaccine hesitancy may influence the acceptance of COVID-19 vaccination. In this cross-sectional study, we aimed to investigate COVID-19 vaccination coverage among healthcare workers (HCWs) in obstetrics and gynecology, during the first three-month period of the vaccination campaign after COVID-19 vaccines were approved. A total of 662 eligible HCWs, consisting of 250 HCWs (group one) who participated in a Jiangsu provincial symposium and 412 HCWs (group two) in the department of obstetrics and gynecology, Nanjing Drum Tower Hospital, were invited to answer a 23-question questionnaire. In total, 618 (93.4%) HCWs completed the questionnaire. The vaccine acceptance in group one was higher than that in group two (87.2% [197/226] vs 74.2% [291/392], χ2 = 14.436, P

Objective Depressive symptoms are known modifiable factors of cognitive impairment in older adults. However, the pathway through which depressive symptoms lead to cognitive impairment is not well understood. This study aimed to investigate whether homebound status (defined as usually unable to leave home unassisted) mediates the association between depressive symptoms and cognitive impairment in community-dwelling older adults in the USA.Design A secondary analysis of cross-sectional data.Setting(s) Communities in the USA.Participants Community-dwelling older adults (N=7537) from the 2011 National Health and Aging Trends Study, a nationally representative survey of Medicare Beneficiaries in the USA.Main outcome measures Participants’ cognitive impairment status was classified using a composite measure. Depressive symptoms were assessed using Patient Health Questionnaire-2. Homebound status was determined by the frequency, difficulty and needing help in getting outdoors. We used logistic regression and the Paramed command in STATA to analyse whether homebound mediated the association between depressive symptoms and cognitive impairment.Results Participants were on average, 77.7 years old, female (58.3%) and non-Hispanic white (68.1%). About 26% of the participants were classified as having cognitive impairment, 16% reported depressive symptoms and 25% were homebound. Depressive symptoms (adjusted OR, 1.60; 95% CI 1.36 to 1.89) and homebound status (adjusted OR, 1.58; 95% CI 1.34 to 1.86) were independently associated with cognitive impairment. Homebound significantly mediated 12.5% of the total effect between depressive symptoms and cognitive impairment, with significant indirect effect (OR, 1.07; 95% CI 1.04 to 1.10), direct effect (OR, 1.61; 95% CI 1.36 to 1.91) and total effect (OR, 1.72; 95% CI 1.46 to 2.03).Conclusions This study supports a mediating role of homebound status in the relationship between depressive symptoms and cognitive impairment. Interventions to promote outdoor mobility should be studied for their ability to delay cognitive impairment for older adults with depressive symptoms.

Buruli ulcer is a chronic skin disease caused by a toxic lipid mycolactone produced by Mycobacterium ulcerans, which induces local skin tissue destruction and analgesia. However, the cytotoxicity pathway induced by mycolactone remains largely unknown. Here we investigated the mycolactone-induced cell death pathway by screening host factors using a genome-scale lenti-CRISPR mutagenesis assay in human premonocytic THP-1 cells. As a result, 884 genes were identified as candidates causing mycolactone-induced cell death, among which SEC61A1, the α-subunit of the Sec61 translocon complex, was the highest scoring. CRISPR/Cas9 genome editing of SEC61A1 in THP-1 cells suppressed mycolactone-induced endoplasmic reticulum stress, especially eIF2α phosphorylation, and caspase-dependent apoptosis. Although previous studies have reported that mycolactone targets SEC61A1 based on mutation screening and structural analysis in several cell lines, we have reconfirmed that SEC61A1 is a mycolactone target by genome-wide screening in THP-1 cells. These results shed light on the cytotoxicity of mycolactone and suggest that the inhibition of mycolactone activity or SEC61A1 downstream cascades will be a novel therapeutic modality to eliminate the harmful effects of mycolactone in addition to the 8-week antibiotic regimen of rifampicin and clarithromycin.

High vaccination coverage is essential to prevent and control the spread of the COVID-19 epidemic. Currently, the real-world acceptance of COVID-19 vaccines among adolescents aged 12–17 years in China has not been reported. We aimed to assess the acceptance rate of COVID-19 vaccination among adolescents in eastern China and to identify factors associated with the intention to get vaccinated against COVID-19. We conduct a cross-sectional questionnaire survey among adolescents from three provinces in the eastern part of China from 16 August to 28 October 2021. The questionnaires were distributed to 2,100 students, and 2,048 students completed the questionnaires. The results showed that 98.4% (2,016/2,048) of adolescents had received at least one dose of the COVID-19 vaccine and 1.6% (32/2,048) declined the vaccination. The participants from rural districts, or whose parents were vaccinated, were more likely to accept the vaccine. The main reason for declining vaccination was worry about vaccine safety (25%). The main adverse event after the vaccination was pain at the injection site. In conclusion, the vaccine coverage rate reached 98.4% among the adolescents in this study, which met the criteria for herd immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The high vaccination rate is beneficial to the prevention and control of the COVID-19 pandemic.

Summary: The global pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection confers great threat to public health. Human breast milk is a complex nutritional composition to nourish infants and protect them from different kinds of infectious diseases including COVID-19. Here, we identified that lactoferrin (LF), mucin1 (MUC1), and α-lactalbumin (α-LA) from human breast milk inhibit SARS-CoV-2 infection using a SARS-CoV-2 pseudovirus system and transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP). In addition, LF and MUC1 inhibited multiple steps including viral attachment, entry, and postentry replication, whereas α-LA inhibited viral attachment and entry. Importantly, LF, MUC1, and α-LA possess potent antiviral activities toward variants such as B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), and B.1.617.1 (kappa). Taken together, our study provides evidence that human breast milk components (LF, MUC1, and α-LA) are promising antiviral and potential therapeutic candidates warranting further development for treating COVID-19.

BackgroundVarious incisions and approaches for thyroidectomy have been developed to treat differentiated thyroid cancer (DTC). Supraclavicular oblique incision (SOI) thyroidectomy (SOIT) has been applied in DTC patients over the past ten years. However, the safety and efficacy of this approach were yet to be confirmed.AimThis study aimed to compare the surgical and patient-related outcomes between SOIT and traditional low collar incision thyroidectomy (TLCIT) in patients with DTC.MethodsWe retrospectively screened all patients with DTC who received thyroid lobectomy from October 2020 to October 2021. The surgical results and patient-related outcomes assessed at 1 and 6 months after surgery by questionnaire were compared between the SOIT and TLCIT groups.ResultsA total of 128 patients were included in this study, of whom 38 patients (30.5%) were operated on with SOIT and 89 patients (69.5%) with TLCIT. There was no significant difference in demographic characteristics and thyroid features between the two groups. Despite comparable operative time (61.9 ± 12.1 vs. 59.9 ± 15.0 min, p = 0.425), the SOIT group had a smaller neck incision (4.4 ± 0.7 vs. 5.0 ± 1.0 cm, p = 0.002), a shorter duration of postoperative drainage (2.4 ± 0.5 vs. 2.7 ± 0.9 days, p = 0.019), less volume of postoperative drainage (48.4 ± 24.6 vs. 60.3 ± 22.8 ml, p = 0.040), and shorter postoperative hospitalization (3.2 ± 0.5 vs. 3.6 ± 0.9 days p = 0.006), as compared with the TLCIT group. At 1-month follow-up after surgery, SOIT showed better performance in preventing hypoparathyroidism (p = 0.026) and abnormal neck sensation (p = 0.010) and in improving cosmetic satisfaction (p = 0.036) than TLCIT. At 6-month follow-up, SOIT was feedback with better cosmetic satisfaction (p < 0.001) and a lower percent of abnormal neck sensation (p = 0.031) or movement (p = 0.005).ConclusionOur study suggests that minimally invasive surgery using the SOI provides superior surgical and patient-related outcomes compared with surgery using a traditional low collar incision (TLCI) in patients with DTC.

Leprosy reactions are acute inflammatory episodes that complicate the course of a Mycobacterium leprae infection and are the major cause of leprosy-associated pathology. Two types of leprosy reactions with relatively distinct pathogenesis and clinical features can occur: type 1 reaction, also known as reversal reaction, and type 2 reaction, also known as erythema nodosum leprosum. These acute nerve-destructive immune exacerbations often cause irreversible disabilities and deformities, especially when diagnosis is delayed. However, there is no diagnostic test to detect or predict leprosy reactions before the onset of clinical symptoms. Identification of biomarkers for leprosy reactions, which impede the development of symptoms or correlate with early-onset, will allow precise diagnosis and timely interventions to greatly improve the patients' quality of life. Here, we review the progress of research aimed at identifying biomarkers for leprosy reactions, including its correlation with not only immunity but also genetics, transcripts, and metabolites, providing an understanding of the immune dysfunction and inflammation that underly the pathogenesis of leprosy reactions. Nevertheless, no biomarkers that can reliably predict the subsequent occurrence of leprosy reactions from non-reactional patients and distinguish type I reaction from type II have yet been found.

In order to investigate the pollution characteristics of size-segregated particles and metal elements (MEs) after the Chinese Air Pollution Prevention Action Plan was released in 2013, an intensive field campaign was conducted in the suburban area of Chaoyang District, Beijing in winter 2016. The size distributions of particle mass concentrations were bimodal, with the first peak in the fine fraction (0.4–2.1 µm) and the second peak in the coarse fraction (3.3–5.8 µm). Moreover, the proportion of fine particles increased and the proportion of coarse particles decreased as the pollution level was more elevated. It was found that the composition of coarse particles is as important as that of fine particles when pollution of aerosol metals in the atmosphere in 2016 were compared to 2013. In addition, according to the size distribution characteristics, 23 MEs were divided into three groups: (a) Fe, Co, Sr, Al, Ti, Ba, and U, which concentrated in coarse mode; (b) Zn, As, Cd, Tl, and Pb, which concentrated in fine mode; and (c) Na, K, Be, V, Cr, Mn, Ni, Cu, Mo, Ag, and Sn, showing bimodal distribution. Under clean air, slight pollution and moderate pollution conditions, most elements maintained their original size distributions, while under severe pollution, the unimodal distributions of most MEs became bimodal distributions. The factors analysis combined with size distributions indicated that Na, Zn, Mo, Ag, Cd, and Tl, showing the moderate to severe contamination on environment, were significantly influenced by diffuse regional emissions or anthropogenic source emissions (vehicle exhaust emissions and combustion process). The environmental risk assessment revealed that the heavy metal loading in the atmospheric particles collected had a high potential for ecological risk to the environment during sampling period because of the high contribution of Cd, Tl, Zn and Pb.

Mycobacterium leprae (M. leprae) is the etiological agent of leprosy, and the skin lesions of lepromatous leprosy are filled with numerous foamy or xanthomatous histiocytes that are parasitized by M. leprae. Lipids are an important nutrient for the intracellular survival of M. leprae. In this study, we attempted to determine the intracellular lipid composition and underlying mechanisms for changes in host cell lipid metabolism induced by M. leprae infection. Using high-performance thin-layer chromatography (HPTLC), we demonstrated specific induction of triacylglycerol (TAG) production in human macrophage THP-1 cells following M. leprae infection. We then used [14C] stearic acid tracing to show incorporation of this newly synthesized host cell TAG into M. leprae. In parallel with TAG accumulation, expression of host glycerol-3-phosphate acyltransferase 3 (GPAT3), a key enzyme in de novo TAG synthesis, was significantly increased in M. leprae-infected cells. CRISPR/Cas9 genome editing of GPAT3 in THP-1 cells (GPAT3 KO) dramatically reduced accumulation of TAG following M. leprae infection, intracellular mycobacterial load, and bacteria viability. These results together suggest that M. leprae induces host GPAT3 expression to facilitate TAG accumulation within macrophages to maintain a suitable environment that is crucial for intracellular survival of these bacilli.

Despite the presence of hepatitis B virus (HBV) in the human breastmilk of mothers infected with HBV, it has been shown that breastfeeding does not increase the risk of mother-to-child transmission (MTCT) of HBV. We tested the hypothesis that human breastmilk may contain active components that bind to HBV and inhibit the infectivity of HBV. The results show that human whey significantly inhibited the binding of the hepatitis B surface antigen (HBsAg) to its antibodies in competitive inhibition immunoassays. The far-western blotting showed that HBsAg bound to a protein of 80 kD in human whey, which was identified as lactoferrin by mass spectrometry. Competitive inhibition immunoassays further demonstrated that both human lactoferrin and bovine lactoferrin bound to HBsAg. Human whey, human lactoferrin, and bovine lactoferrin each significantly inhibited the infectivity of HBV in vitro. Our results indicate that human breastmilk can bind to HBsAg and inhibit the infectivity of HBV, and the active component is lactoferrin. The findings may explain the reason that breastfeeding has no additional risk for MTCT of HBV, although human breastmilk contains HBV. Our study provides experimental evidence that HBV-infected mothers should be encouraged to breastfeed their infants

Prunella vulgaris (PV), a perennial herb, has been used to treat thyroid diseases in China for over 2,000 years. In particular, its therapeutic effect has been described for Hashimoto’s thyroiditis, including reducing titers autoantibodies against thyroid peroxidase and thyroglobulin of and T helper 17 (Th17) cells. However, the underlying mechanism for how PV exerts such effects has not been investigated. We examined the effects of PV on innate immune activation, which is thought to be one of the triggers for the development of autoimmune diseases, including Hashimoto’s thyroiditis. In cultured thyrocytes, PV reduced mRNA levels of inflammatory cytokines that were originally induced as a result of innate immune activation initiated by transfection of double-stranded DNA (dsDNA) or dsRNA. PV suppressed activation of nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF3), and suppressed corresponding promoter activation, which were initially activated by dsDNA or dsRNA. PV also suppressed the mRNA levels of molecules responsible for antigen processing and presentation, and PV protected thyrocytes from apoptosis induced by dsDNA and dsRNA. Additionally, PV suppressed the expression of genes involved in iodide uptake and oxidation. Taken together, these results suggest that PV exerts its protective effect on thyrocytes by suppressing both innate and adaptive immune responses and cell death. PV may also protect cells from iodide-associated oxidative injury. This report is among the first to identify the mechanisms to explain PV’s beneficial effects in Hashimoto’s thyroiditis.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae). In lepromatous leprosy (LL), skin macrophages, harboring extensive bacterial multiplication, gain a distinctive foamy appearance due to increased intracellular lipid load. To determine the mechanism by which M. leprae modifies the lipid homeostasis in host cells, an in vitro M. leprae infection system, using human macrophage precursor THP-1 cells and M. leprae prepared from the footpads of nude mice, was employed. RNA extracted from skin smear samples of patients was used to investigate host gene expressions before and after multidrug therapy (MDT). We found that a cluster of peroxisome proliferator-activated receptor (PPAR) target genes associated with adipocyte differentiation were strongly induced in M. leprae-infected THP-1 cells, with increased intracellular lipid accumulation. PPAR-δ and PPAR-γ expressions were induced by M. leprae infection in a bacterial load-dependent manner, and their proteins underwent nuclear translocalization after infection, indicating activation of PPAR signaling in host cells. Either PPAR-δ or PPAR-γ antagonist abolished the effect of M. leprae to modify host gene expressions and inhibited intracellular lipid accumulation in host cells. M. leprae-specific gene expressions were detected in the skin smear samples both before and after MDT, whereas PPAR target gene expressions were dramatically diminished after MDT. These results suggest that M. leprae infection activates host PPAR signaling to induce an array of adipocyte differentiation-associated genes, leading to accumulation of intracellular lipids to accommodate M. leprae parasitization. Certain PPAR target genes in skin lesions may serve as biomarkers for monitoring treatment efficacy.

Pentasachme caudatum Wallich ex Wight is considered as one of the Asian enigmatic genera classified in the Asclepiadoideae (Apocynaceae). To determine its evolutionary relationship in the family, we sequenced and characterized the complete chloroplast genome of P. caudatum. The plastid genome of P. caudatum is 158,487 bp in length, containing a large single-copy (90,380 bp), a small single-copy (18,585 bp), and a pair of inverted repeats (24,761 bp). It has 127 annotated genes, consisting of 83 protein-coding, eight rRNA and 36 tRNA genes. Phylogenetic analysis using 76 protein-coding regions of the plastid genomes of related taxa showed that P. caudatum was resolved in a fully supported clade with Orthanthera albida. The newly sequenced P. caudatum provides essential genetic information that is useful for future phylogenetic studies in the family Apocynaceae.

The mycobacterial cell wall is composed of large amounts of lipids with varying moieties. Some mycobacteria species hijack host cells and promote lipid droplet accumulation to build the cellular environment essential for their intracellular survival. Thus, lipids are thought to be important for mycobacteria survival as well as for the invasion, parasitization, and proliferation within host cells. However, their physiological roles have not been fully elucidated. Recent studies have revealed that mycobacteria modulate the peroxisome proliferator-activated receptor (PPAR) signaling and utilize host-derived triacylglycerol (TAG) and cholesterol as both nutrient sources and evasion from the host immune system. In this review, we discuss recent findings that describe the activation of PPARs by mycobacterial infections and their role in determining the fate of bacilli by inducing lipid metabolism, anti-inflammatory function, and autophagy.

The global effort to prevent iodine deficiency disorders through iodine supplementation, such as universal salt iodization, has achieved impressive progress during the last few decades. However, iodine excess, due to extensive environmental iodine exposure in addition to poor monitoring, is currently a more frequent occurrence than iodine deficiency. Iodine excess is a precipitating environmental factor in the development of autoimmune thyroid disease. Excessive amounts of iodide have been linked to the development of autoimmune thyroiditis in humans and animals, while intrathyroidal depletion of iodine prevents disease in animal strains susceptible to severe thyroiditis. Although the mechanisms by which iodide induces thyroiditis are still unclear, several mechanisms have been proposed: (1) excess iodine induces the production of cytokines and chemokines that can recruit immunocompetent cells to the thyroid; (2) processing excess iodine in thyroid epithelial cells may result in elevated levels of oxidative stress, leading to harmful lipid oxidation and thyroid tissue injuries; and (3) iodine incorporation in the protein chain of thyroglobulin may augment the antigenicity of this molecule. This review will summarize the current knowledge regarding excess iodide as an environmental toxicant and relate it to the development of autoimmune thyroid disease.

The microflora in environmental water consists of a high density and diversity of bacterial species that form the foundation of the water ecosystem. Because the majority of these species cannot be cultured in vitro, a different approach is needed to identify prokaryotes in environmental water. A novel DNA microarray was developed as a simplified detection protocol. Multiple DNA probes were designed against each of the 97,927 sequences in the DNA Data Bank of Japan and mounted on a glass chip in duplicate. Evaluation of the microarray was performed using the DNA extracted from one liter of environmental water samples collected from seven sites in Japan. The extracted DNA was uniformly amplified using whole genome amplification (WGA), labeled with Cy3-conjugated 16S rRNA specific primers and hybridized to the microarray. The microarray successfully identified soil bacteria and environment-specific bacteria clusters. The DNA microarray described herein can be a useful tool in evaluating the diversity of prokaryotes and assessing environmental changes such as global warming.

Graves’ hyperthyroidism is caused by autoantibodies directed against the thyroid stimulating hormone receptor (TSHR) that mimic the action of TSH. The establishment of Graves’ hyperthyroidism in experimental animals has proven to be an important approach to dissect the mechanisms of self-tolerance breakdown that lead to the production of thyroid-stimulating TSHR autoantibodies (TSAbs). ‘Shimojo’s model was the first successful Graves’ animal model, wherein immunization with fibroblasts cells expressing TSHR and a major histocompatibility complex (MHC) class II molecule, but not either alone, induced TSAb production in AKR/N (H-2k) mice. This model highlights the importance of coincident MHC class II expression on TSHR-expressing cells in the development of Graves’ hyperthyroidism. These data are also in agreement with the observation that Graves’ thyrocytes often aberrantly express MHC class II antigens via mechanisms that remain unclear. Our group demonstrated that cytosolic self-genomic DNA fragments derived from sterile injured cells can induce aberrant MHC class II expression and production of multiple inflammatory cytokines and chemokines in thyrocytes in vitro, suggesting that severe cell injury may initiate immune responses in a way that is relevant to thyroid autoimmunity mediated by cytosolic DNA signaling. Furthermore, more recent successful Graves’ animal models were primarily established by immunizing mice with TSHR-expressing plasmids or adenovirus. In these models, double-stranded DNA vaccine contents presumably exert similar immune-activating effect in cells at inoculation sites and thus might pave the way toward successful Graves’ animal models. This review focuses on evidence suggesting that cell injury-derived self-DNA fragments could act as Graves’ disease triggers.

The Nabe-kaburi is a unique burial method, the purpose of which is shrouded in mystery. The burials were performed during the 15(th) to 18(th) centuries in eastern Japan, and involved covering the heads of the deceased with iron pots or mortars. The identification of leprosy-specific osteological lesions among some of the excavated remains has led to the suggestion that Nabe-kaburi burials were a reflection of the social stigma against certain infectious diseases, such as leprosy, tuberculosis or syphilis. However, molecular evidence for the presence of disease has been lacking. The goal of this study was to detect Mycobacterium leprae (M. leprae) DNA in archaeological human skeletal remains from Nabe-kaburi burials. The paleopathological data from three Nabe-kaburi burials were re-evaluated before small samples were taken from affected and control areas. DNA was extracted and used as a template to target the M. leprae-specific DNA using a combination of whole genome amplification, PCR analysis and DNA sequencing. M. leprae DNA fragments were detected in the two sets of skeletal remains that had also shown paleopathological evidence of leprosy. These findings provide definitive evidence that some of the Nabe-kaburi burials were performed for people affected by leprosy. Demonstration of the presence of M. leprae DNA, combined with archeological and anthropological examinations, will aid in solving the mystery of why Nabe-kaburi burials were performed in medieval Japan.