Integrative Transcriptome and Metabolome Analysis to Reveal Red Leaf Coloration in Shiya Tea (Adinandra nitida).

BACKGROUND: Adinandra nitida, commonly known as Shiya tea, is a healthcare drink enriched in several phenolic acids and flavonoids, with a purple-red leaf variety possessing a unique flavor and a higher economic value. However, the mechanisms underlying leaf coloration and senescence discoloration remain unknown. METHODS: Here, we compared both varieties of A. nitida (purple-red leaf, RL, and green leaf, GL) at two stages of development. To make sure the difference in leaf color in these four groups, several indexes, leaf colorimetric differences, H2O2 content in leaf cells, and antioxidant enzymes activities (superoxide dismutase (SOD), catalase (CAT)) were measured. With the integration of metabolome and transcriptome becoming a trend, metabolites in four groups were detected using an Ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) system, and the transcriptome was performed after the extraction of RNA in samples. Afterward, the activities of laccase (LAC) and peroxidase (POD) were measured for further analysis. RESULTS: The deeper or discoloration of leaf color was not caused by the reactive oxygen species (ROS) stress because the H2O2 content was similar for each group. And the SOD and CAT activities improved significantly in young leaves, especially RL_young. Metabolome data showed a large shift in four groups. By focusing on the variation of flavonoids and 1079 metabolites detected in both varieties, along with the accumulation of flavonoids and tannins, proanthocyanins (PAs) were mostly accumulated in young RL. Differential analysis of expressed genes (DEGs) revealed six genes associated with leaf discoloration as hub factors, of which ANRs (ANR1 and ANR2) were positively correlated with the accumulation of PA in RL. CONCLUSIONS: Using integrate analysis of metabolome and transcriptome, our results revealed that six structural genes found in proanthocyanin biosynthesis, two reductases (ANR), two oxidative polymerases (POD64, LAC17) and two TFs (bHLH3 and MYB4) related to biosynthesis and polymerization of proanthocyanins were associated with not only the difference of GL and RL but also the faded coloration in two RL groups (RL_young and RL_old), which provided a foundation for further research on an understanding of the regulatory genes and the enzymes specific for proanthocyanidin biosynthesis, facilitating the genetic engineering of crops for beneficial metabolite accumulation.

Orthodontic alignment of ankylosed teeth with aid of surgical luxation: Case series.

BACKGROUND: Identification of tooth ankylosis before comprehensive orthodontic treatment can be challenging. This case series illustrates different presentations of tooth ankylosis, the importance of early diagnosis, the use of surgical luxation to aid orthodontic alignment of ankylosed teeth and its sequelae. CASE PRESENTATION: All three cases were adolescents: a 14-year-old girl with a highly placed upper left lateral incisor and history of general anaesthesia; a 14-year-old boy with an impacted upper right first premolar and history of dental trauma; and a 13-year-old girl with an infraoccluded upper left central incisor with history of replantation due to avulsion. Iatrogenic malocclusion developed from attempts to align ankylosed teeth. Subsequently, surgical luxation was performed, and the ankylosed teeth were successfully aligned. However, it was associated with pulp calcification, root resorption and recurrence of ankylosis. CONCLUSION: Surgical luxation and orthodontic alignment of ankylosed teeth can be considered a useful short-term solution to delay the need of surgical removal and teeth replacement.

Elevated Interleukin-37 Associated with Dengue Viral Load in Patients with Dengue Fever.

Dengue remains a public health issue worldwide. Similar to chronic infectious diseases, stimulation of cytokine production is not enough to drive immune effector cells for effective virus clearance. One possible mechanism is the virus induces a large number of negative stimulatory cytokines inhibiting immune response. Interleukin 37 (IL-37) plays a crucial regulatory role in infection and immunity, inhibits innate and adaptive immunity as an anti-inflammatory cytokine by inhibiting proinflammatory mediators and pathways. To date, there are few studies reporting correlations between dengue fever (DF) and IL-37. In this study we found that the serum IL-37b and IL-37b-producing monocytes in patients were significantly increased in DF patients. A majority of the IL-37b produced by DF patients was produced by monocytes, not lymphocytes. Increased levels of IL-6, IL-10, and IFN-α were also found in DF patients. However, we failed to detect IL-1ß, IL-17A and TNF-α in plasma, because of off-target. In our study, there was no relation between IL-6, IL-10, and IFN-α expressions and IL-37b in serum (P > 0.05). The IL-37b-producing monocytes were negatively correlated with the level of IFN-α in serum and platelet count, and positively correlated with lymphocytes percentage (P < 0.05, respectively). Additionally, serum DENV nonstructural protein 1 levels were positively correlated with monocytes percentages (P < 0.05). Our data represents findings for IL-37b expression and its potential mechanisms in DF patients' immune response.

Evaluation of Dental Students’ Medical History Records on Hypertension and Diabetes Mellitus at The National University of Malaysia

@#Introduction: A thorough medical history ensures safe dental practice. A good medical history guides clinicians in risk stratification to avoid medical emergencies and improve preparedness to prevent patient morbidity and mortality. This clinical audit aims to analyse the medical history taken by the dental students in patients with hypertension and/or diabetes mellitus (DM) and subsequently, recommend improvements in history-taking components in the dental practice. Methods: Hundred and two patients’ folders from the Faculty of Dentistry were examined by two independent auditors using a validated history-taking evaluation form. Six components of the medical history were classified as good or bad practices. Sociodemographic factors and distribution of the American Society of Anesthesiologists (ASA status) were described. The level of completeness of medical history records with years of study was assessed using the Chi-square test. Results: None of the students met 100% of the components required in medical history taking. Year three undergraduates performed poorly in the completeness of diagnosis and control of the medical condition whereby none of them had a good level of practice. The completeness of records did not differ between years of study except for diagnosis (p=0.026), control (p<0.001) and updating medical history (p=0.009) whereby the postgraduates had the best practice. Conclusion: This study highlighted marked deficiencies in taking a thorough medical history. Adaptation of the European Medical Risk Related History (EMRRH) form is recommended to be implemented in dental schools.

Meta-analysis and trial sequential analysis of Compound Qinlan Oral Liquid in treatment of acute upper respiratory tract infection / 中国中药杂志

This study aims to evaluate the efficacy and safety of Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. Computer-based online searching of CNKI, VIP, SinoMed, Wanfang, ChiCTR, ClinicalTrials.gov, Cochrane Library, PubMed, EMbase, and Web of Science was performed to retrieve the randomized controlled trial(RCT) regarding Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. In addition, manual searching of gray literature was conducted. After two evaluators independently selected articles, extracted data, and evaluated the quality of methodology included in the studies, Meta-analysis was carried out in RevMan 5.4 and trial sequential analysis(TSA) in TSA 0.9.5.10 Beta. GRADE profiler 3.6.1 was employed to evaluate the evidence quality. A total of 21 RCTs were included in this study, involving 2 651 patients(1 330 patients in the observation group and 1 321 patients in the control group). Meta-analysis showed that compared with conventional western medicine alone, Compound Qinlan Oral liquid improved the total response rate(RR=1.15, 95%CI[1.12, 1.19], P<0.000 01) without increasing the incidence of adverse reactions(RR=0.77, 95%CI[0.47, 1.25], P=0.16). The results of subgroup analysis are described as follows:(1) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid improved the total response rate(RR=1.10, 95%CI[1.05, 1.14], P<0.000 01) and shortened the time to symptom relief(SMD=-0.76, 95%CI[-1.02,-0.51], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=1.16, 95%CI[0.54, 2.47], P=0.71).(2) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid + conventional western medicine improved the total response rate(RR=1.20, 95%CI[1.15, 1.25], P<0.000 01), decreased traditional Chinese medicine(TCM) syndrome scores(MD=-0.58, 95%CI[-0.75,-0.41], P<0.000 01), shortened the time to symptom relief(SMD=-2.44, 95%CI[-3.09,-1.80], P<0.000 01) and physical sign improvement(MD=-2.57, 95%CI[-4.11,-1.04], P=0.001), lowered the serum levels of inflammatory cytokines(SMD=-2.16, 95%CI[-2.61,-1.70], P<0.000 01), improved respiratory function indicators(SMD=1.48, 95%CI[1.00, 1.96], P<0.000 01), and enhanced the humoral immunity(MD=0.94, 95%CI[0.69, 1.18], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=0.57, 95%CI[0.29, 1.09], P=0.09). TSA showed that the cumulative Z curve of total response rate crossed the traditional threshold and TSA threshold, further confirming the clinical efficacy of Compound Qinlan Oral Liquid. The GRADE graded the evidence of the above outcome indicators as low or extremely low, and yielded weak recommendation. Compared with conventional western medicine alone, Compound Qinlan Oral Liquid can improve the total effective rate and reduce the time to symptom relief. The combination of Compound Qinlan Oral Liquid and conventional western medicine can improve the total response rate, mitigate the symptoms and improve the physical signs, reduce inflammation, and improve respiratory function and immunity of the patients with acute upper respiratory tract infection. In view of the limited number and quality of the included studies, the above conclusions still require high-quality RCT to provide evidence support.

Meta-analysis and trial sequential analysis of Chaihuang Granules in treatment of upper respiratory tract infection in children / 中国中药杂志

This study aimed to evaluate the efficacy and safety of Chaihuang Granules in the treatment of upper respiratory tract infection in children. The databases such as CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched for randomized controlled trial(RCT) of Chaihuang Granules for the treatment of upper respiratory tract infection in children, and supplemented by manual searching of gray literature. Two investigators independently screened the literature, extracted data, and assessed the methodological quality. Meta-analysis was performed using RevMan 5.4 software, trial sequential analysis was conducted using TSA 0.9.5.10 Beta software, and evidence quality evaluation was carried out using GRADE profiler 3.6.1 software. Eighteen RCTs involving 2 459 patients(1 262 in the treatment group and 1 197 in the control group) were included. Meta-analysis showed that compared with conventional therapy alone, Chaihuang Granules significantly improved the total effective rate(RR=1.18, 95%CI[1.15, 1.22], P<0.000 01), reduced the disappearance time of symptoms/signs(MD=-1.39, 95%CI[-1.66,-1.12], P<0.000 01), improved cytokine levels(MD=-2.40, 95%CI[-3.80,-1.00], P=0.000 8), improved humoral immune levels(MD=0.75, 95%CI[0.60, 0.90], P<0.000 01), and reduced the recurrence rate(MD=-2.11, 95%CI[-2.98,-1.25], P<0.000 01). However, the incidence of adverse reactions was not increased(RR=0.94, 95%CI[0.59, 1.49], P=0.78). Subgroup analysis showed that:(1) both Chaihuang Granules used alone(RR=1.19, 95%CI[1.11, 1.27], P<0.000 01) and in combination with other therapies(RR=1.18, 95%CI[1.14, 1.22], P<0.000 01) effectively improved the total effective rate.(2) In terms of symptoms/signs disappearance time, Chaihuang Granules effectively reduced the duration of fever(MD=-1.18, 95%CI[-1.78,-0.58], P=0.000 1), cough with sputum(MD=-1.82, 95%CI[-2.38,-1.25], P<0.000 01), cough(MD=-1.31, 95%CI[-1.89,-0.74], P<0.000 01), sore throat(MD=-1.57, 95%CI[-2.25,-0.89], P<0.000 01), and lung rales(MD=-1.49, 95%CI[-2.06,-0.92], P<0.000 01).(3) Regarding cytokine levels, Chaihuang Gra-nules effectively improved the levels of interleukin(IL)-2(MD=-0.94, 95%CI[-1.16,-0.72], P<0.000 01), IL-6(MD=-4.71, 95%CI[-6.39,-3.03], P<0.000 01), and tumor necrosis factor-α(TNF-α)(MD=-2.07, 95%CI[-2.43,-1.71], P<0.000 01).(4) In terms of cellular immune levels, Chaihuang Granules effectively improved the levels of CD3~+(MD=4.11, 95%CI[1.53, 6.69], P=0.002), CD4~+(MD=4.21, 95%CI[1.69, 6.73], P=0.001), CD8~+(MD=-2.65, 95%CI[-3.93,-1.37], P<0.000 1), and CD4~+/CD8~+(MD=0.25, 95%CI[0.14, 0.37], P<0.000 1).(5) In terms of humoral immune levels, Chaihuang Granules effectively improved the levels of IgA(MD=0.44, 95%CI[0.23, 0.64], P<0.000 1), IgM(MD=0.31, 95%CI[0.15, 0.46], P=0.000 1), and IgG(MD=2.02, 95%CI[1.60, 2.43], P<0.000 01). Trial sequential analysis showed that the cumulative Z-curve of the total effective rate crossed the boundary value, further confirming its clinical efficacy. The GRADE evidence quality evaluation showed that the evidence quality of the above outcome indicators was low or very low, and the recommendation strength was weak. Compared to conventional therapy alone, Chaihuang Granules can effectively improve the total effective rate of treatment, alle-viate symptoms and signs of upper respiratory tract infection in children, improve inflammatory conditions, enhance immune function, and reduce the recurrence rate. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.

Molecular aggregation via partial Gal removal affects physicochemical and macromolecular properties of tamarind kernel polysaccharides.

The role of molecular aggregation was investigated on physicochemical and macromolecular properties of tamarind kernel polysaccharides via partial degalactosylation (TKPs vs. CTKPs). From the results, their main structural characteristics remained when partially degalactosylated, while primary aggregates as fundamental solution behavior were dynamically converted into higher aggregated forms. Micromorphologically, their conformational changes in different forms of crimping and aggregation could be further promoted by partial Gal removal to assemble on larger scales via hydrophobic interactions. Obviously, the aggregation role was unignorable, especially after partial degalactosylation, which affected TKPs and CTKPs differently concerning viscous behaviors, macromolecular characteristics, amorphous-crystalline transition and thermal stability, probably related to distinctiveness in polymerization degree, chemical structure, conformational entropy, solvent-solute interactions, specific intermolecular associations, etc. Therefore, molecular aggregation in tamarind kernel polysaccharides via specific Gal tailoring could be potential in applicable fields, such as postsurgical adhesion, packaging material design and plasma lipid metabolism.

Pectic polysaccharides from Biluochun Tea: A comparative study in macromolecular characteristics, fine structures and radical scavenging activities in vitro.

In this study, two acidic Biluochun Tea polysaccharides (BTP-A11 and BTP-A12) were investigated comparatively, which mainly consisted of Rha, Ara, Gal and GalA, possibly suggesting their pectic nature. Structurally, their galacturonan backbones composed of →4)-α-D-GalpA-(1→ and →2)-α-L-Rhap-(1→ were revealed similar, while Ara- and Gal-based branches attached to the O-2 of →2)-α-L-Rhap-(1→ were in distinctive types, proportions, extensibilities and branching degrees. This could lead to their different macromolecular characteristics, where BTP-A11 with higher Mw presented a more hyper-branched chain conformation and relatively higher structural flexibility/compactness, thereby resulting in a lower exclusion effect and an insufficient hydrodynamic volume. Besides, better radical scavenging activities in vitro were also determined for Gal-enriched BTP-A11, where a larger surface area containing more H-donating groups were related to its higher Mw, more hyper-branched conformation, lower DM and higher DA. Therefore, the understanding of structure-property-activity relationships was improved to some degrees for acidic Biluochun Tea polysaccharides, which could be potentially required for more applications in food, medical and cosmetic fields.

A multi-center study on effect of low serum albumin levels and duration on first episode of peritonitis in continuous ambulatory peritoneal dialysis / 中华肾脏病杂志

Objective:To explore the relationship between low serum albumin levels and its duration on first episode of peritonitis in peritoneal dialysis (PD) patients.Methods:PD patients who were regularly followed up in the Pearl River Delta region from September 1, 2000 to July 6, 2021 in Shunde Hospital of Southern Medical University, Nanfang Hospital of Southern Medical University, and Foshan First People′s Hospital were retrospectively selected. The patients were divided into low serum albumin group (LSA group, mean albumin<35 g/L), moderate serum albumin group (MSA group, 35 g/L≤mean albumin<40 g/L) and high serum albumin group (HSA group, mean albumin≥40 g/L) according to the mean albumin of the patients, and the differences among the three groups were compared. The Kaplan-Meier survival analysis method was used to compare the risk of peritonitis events in different mean albumin groups and different durations of hypoalbuminemia. The multivariate Cox regression model was used to analyze the relationship between serum albumin levels and duration of hypoalbuminemia and new-onset peritonitis.Results:A total of 1 853 PD patients were included in this study, aged (49.72±15.34) years, and 1 036(55.9%) males. There were 551 patients (29.7%) in the LSA group, 920 patients (49.7%) in the MSA group, and 382 patients (20.6%) in the HSA group. The median follow-up was 37 (15, 66) months and there were 508 patients (27.4%) with new-onset peritonitis during the follow-up. Compared with the LSA group, the incidence of new peritonitis in the MSA group and HSA group was lower ( χ2=14.053, P<0.001; χ2=21.857, P<0.001), but there was no significant difference in the incidence of new peritonitis between the HSA group and MSA group. The Kaplan-Meier survival analysis showed that the cumulative incidence of peritonitis in the LSA group was significantly higher than that in the MSA group and HSA group (Log-rank χ2=22.128, P<0.001). Compared with PD patients with normal serum albumin, the patients with longer duration of hypoalbuminemia tended to have a higher incidence of new peritonitis. Multivariate Cox regression analysis showed that the mean albumin<35 g/L (LSA group/MSA group, HR=1.495, 95% CI 1.198-1.866, P<0.001; LSA group/HSA group, HR=1.459, 95% CI 1.104-1.928, P=0.008) was an independent risk factor of new-onset peritonitis in PD patients and the prolongation of duration of hypoalbuminemia had a significantly higher risk of new-onset peritonitis ( HR=1.013, 95% CI 1.003-1.024, P=0.014). Conclusion:The mean albumin<35 g/L and prolong duration of hypoalbuminemia are independent risk factors of PD-related peritonitis in PD patients.

Effect of Curcumin on Diabetic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Clinical Trials.

BACKGROUND: Curcumin, a polyphenolic constituent from Curcuma longa, possesses antioxidant, hypolipidemic, and antidiabetic properties and has been reported to protect against diabetic kidney disease (DKD); however, the effect is inconsistent. OBJECTIVE: This systematic review and meta-analysis aimed to investigate the effect of curcumin supplementation on renal function, lipid profile, blood pressure, and glycemic control in DKD. METHODS: A systematic and comprehensive literature search of interrelated randomized controlled trials (RCTs) was conducted in PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov from inception to July 30, 2021. Two investigators independently extracted data and assessed the risk of bias. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated to describe the effect sizes using a fixed-effect model. Statistical analysis was performed using STATA 14.0 and RevMan 5.3. RESULTS: Five RCTs involving 290 participants with DKD were included. Curcumin supplementation significantly improved the serum creatinine (WMD: -0.16 mg/dL, 95% CI: -0.3 to -0.02, P = 0.029, I 2 = 0%, moderate certainty), total cholesterol (WMD: -10.13 mg/dL, 95% CI: -17.84 to -2.14, P = 0.01, I 2 = 0%, moderate certainty), systolic blood pressure (WMD: 3.94 mmHg, 95% CI: 1.86 to 6.01, P < 0.01, I 2 = 33.5%, moderate certainty), and fasting blood glucose (WMD: -8.29 mg/dL, 95% CI: -15.19 to -1.39, P = 0.019, I 2 = 43.7%, moderate certainty) levels; however, it had no significant effects on blood urea nitrogen, proteinuria, triglyceride, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and diastolic blood pressure levels. CONCLUSIONS: Curcumin may provide great potential effects against DKD. More large-scale and high-quality RCTs are required to confirm these findings.

Macromolecular and thermokinetic properties of a galactomannan from Sophora alopecuroides L. seeds: A study of molecular aggregation.

The molecular aggregation of a galactomannan (NSAP-25) from Sophora alopecuroides L. seeds was investigated, where three polydisperse systems were confirmed during particle size analysis, indicating existence of different aggregates composed of random coil chains revealed by circular dichroism. Morphologically, NSAP-25 aggregate of various sizes (200-1200 nm) was possibly multi-stranded and formed by ellipsoid-like particles (20-60 nm) composed of compact coil chain, exhibiting extended amorphous structure with chain-like branches intertwined. Hence, NSAP-25 aggregation was inevitable, which exerted an unignorable effect on augmenting flexibility (ß↓, γ↓, α↓ and Lp/ML↓) and compactness (ρ↓, df↑ and C∞↓) of branched random coil chain based on macromolecular analysis, especially when concentration increased. Moreover, it could be relevant to thermokinetic behavior of random nucleation and subsequent growth (A2 model and negative ΔS*) as well as good thermal stability (IPDT, ITS, t0.05, Tm and Tp), thus conferring potential applications for NSAP-25 in food and pharmaceutical industries.

Circular RNA TRAPPC6B inhibits intracellular Mycobacterium tuberculosis growth while inducing autophagy in macrophages by targeting microRNA-874-3p.

OBJECTIVES: Genetic and epigenetic mechanisms regulate antimicrobial immunity against Mycobacterium tuberculosis (Mtb) infection. METHODS: The present study assessed circular RNA TRAPPC6B (circTRAPPC6B) for antimicrobial immune functions and defined mechanisms wherein circTRAPPC6B regulates Mtb growth, autophagy and microRNA in macrophages. RESULTS: The Mtb infection of monocytes/macrophages resulted in a significantly decreased level of circTRAPPC6B that inhibited intracellular Mtb growth in macrophages. Conversely, circTRAPPC6B expression enhanced autophagy or autophagy-associated protein LC3-II production in Mtb-infected macrophages. circTRAPPC6B-enhanced autophagy aggregation or sequestration was also observed in fluorescence in situ hybridisation (FISH) analysis and confocal imaging. Mechanistically, circTRAPPC6B targets an inhibiting element miR-874-3p, as shown by bioinformatics, dual-luciferase reporter gene analysis and pull-down assay, respectively. Notably, miR-874-3p prohibited autophagy via suppressing autophagy protein ATG16L1 by binding to its 3'-untranslated region (UTR) in Mtb-infected macrophages and thus promoting intracellular Mtb growth. Concurrently, circTRAPPC6B enhanced autophagy in Mtb-infected macrophages by blocking the ability of miR-874-3p to inhibit ATG16L1. Thus, circTRAPPC6B antagonises the ability of miR-874-3p to suppress ATG16L1 expression and activate and enhance autophagy sequestration to restrict Mtb growth in macrophages. CONCLUSION: The current findings suggested that both circTRAPPC6B and miR-874-3p mechanisms can be explored as potential therapeutics against Mtb infection.

[Corrigendum] CCL22 and IL­37 inhibit the proliferation and epithelial­mesenchymal transition process of NSCLC A549 cells.

Subsequently to the publication of the above paper, the authors have drawn to our attention that, owing to errors made in the compilation of the images in Fig. 6, the images shown in Fig. 6A­C in the article were selected incorrectly (essentially, the images shown in Fig. 6A and B were alterative presentations of the same data shown in Fig. 6C). The authors were able to re­examine the original data files and retrieve the correct data panels. The revised version of Fig. 6, featuring the corrected data panels for Fig. 6A­C, is shown opposite. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in Oncology Reports 36: 2017-2024, 2016; DOI: 10.3892/or.2016.4995].

Elevation in the counts of IL-35-producing B cells infiltrating into lung tissue in mycobacterial infection is associated with the downregulation of Th1/Th17 and upregulation of Foxp3+Treg.

IL-35 is an anti-inflammatory cytokine and is thought to be produced by regulatory T (Treg) cells. A previous study found that IL-35 was upregulated in the serum of patients with active tuberculosis (ATB), and IL-35-producing B cells infiltrated to tuberculous granuloma of patients with ATB. Purified B cells from such patients generated more IL-35 after stimulation by antigens of Mycobacterium tuberculosis and secreted more IL-10. However, the function and the underlying mechanisms of IL-35-producing B cells in TB progression have not been investigated. The present study found that the expression of mRNA of IL-35 subsets Ebi3 and p35 was elevated in mononuclear cells from peripheral blood, spleen, bone marrow, and lung tissue in a mouse model infected with Mycobacterium bovis BCG, as tested by real-time polymerase chain reaction. Accordingly, the flow cytometry analysis showed that the counts of a subset of IL-35+ B cells were elevated in the circulating blood and in the spleen, bone marrow, and lung tissue in BCG-infected mice, whereas anti-TB therapy reduced IL-35-producing B cells. Interestingly, BCG infection could drive the infiltration of IL-35-producing B cells into the lung tissue, and the elevated counts of IL-35-producing B cells positively correlated with the bacterial load in the lungs. Importantly, the injection of exogenous IL-35 stimulated the elevation in the counts of IL-35-producing B cells and was associated with the downregulation of Th1/Th17 and upregulation of Foxp3+Treg.The study showed that a subset of IL-35-producing B cells might take part in the downregulation of immune response in mycobacterial infection.

The Heritability of Palatal Rugae Morphology Among Siblings*, †.

Although there is clinical applicability of the palatal rugae as an identification tool in forensic odontology, controversy exists whether the palatal rugae patterns are stable or variable. The greater the genetic component, the higher the probability that palatal rugae patterns are stable. The aim of this study was to compare the palatal rugae morphology between full siblings and the proportion of variability due to genetic component. This cross-sectional study was conducted on digital models of 162 siblings aged 15-30 years old. The palatal rugae patterns were assessed with Thomas and Kotze (1983) classification using Geomagic Studio software (3D Systems, Rock Hill, SC). The palatal rugae morphology between siblings showed significantly similar characteristics for total number of left rugae (p = 0.001), left primary rugae (p = 0.017), secondary rugae for right (p = 0.024) and left sides (p = 0.001), right straight rugae (p = 0.010), and right convergent rugae (p = 0.005) accounting for at least 6.25%-12.8% of the variability due to heredity. Despite the similarities found, the palatal rugae patterns showed significant differences between siblings of at least 46.9% (p = 0.001). Zero heritability was found in 9 of the 14 rugae patterns. Meanwhile, total number of rugae, primary, backward, and convergent rugae showed moderate heritability (h2  > 0.3) and total number of secondary rugae showed high heritability (h2  > 0.6). In conclusion, despite the individuality characteristics, an appreciable hereditary component is observed with significant similarities found between sibling pairs and the palatal rugae patterns were both environmentally and genetically influenced.

Morphological patterns of the palatal rugae: A review.

BACKGROUND: Palatal rugae are asymmetric ridges of connective tissue located behind the incisive papilla over the anterior hard palate. They serve as stable superimposition landmarks to assess tooth movement in orthodontics and as identification aids in forensic odontology. However, the stability of palatal rugae remains controversial. This review aimed to describe the genetic, growth, and environmental factors that may influence the palatal rugae patterns. A broad search of PubMed and ScienceDirect databases was conducted. A total of 193 articles were identified, of which 73 met the selection criteria. Data were extracted into a table that presented the details of the study, sample description, and changes in the palatal rugae patterns. HIGHLIGHT: There were conflicting results regarding sexual dimorphism and population characterization of the palatal rugae patterns. All rugae showed positional changes, increased lengths, and lower numbers, but no significant shape changes with growth. The lengths, numbers, and positions of the rugae were affected by orthodontic treatment, especially their lateral points, but their individual characteristics did not change. CONCLUSION: The diversity in rugae patterns and their potential for sex discrimination among different populations showed differing results due to individual variations and the complex influence of genetic, growth, and environmental factors on their morphology.

Circular RNA hsa_circ_0001380 in peripheral blood as a potential diagnostic biomarker for active pulmonary tuberculosis.

Numerous studies have suggested that circular RNAs (circRNAs), a type of non­coding RNA lacking 5'­caps and 3'­poly(A) tails, are involved in the biological processes of various human diseases. However, little is known about their functions and diagnostic value in active pulmonary tuberculosis (APTB). The aim of the present study was to examine whether hsa_circ_0001380 is able to serve as a diagnostic biomarker for patients with APTB. The expression level of hsa_circ_0001380 was detected in the peripheral blood of 32 patients with APTB and 31 healthy volunteers by reverse transcription­quantitative PCR. The functional prediction of hsa_circ_0001380 was performed in silico. RNase R was used to detect the stability of hsa_circ_0001380. Finally, the diagnostic value of hsa_circ_0001380 was evaluated by receiver operating characteristic (ROC) curve analysis. The results showed that hsa_circ_0001380 was significantly downregulated in the peripheral blood of patients with APTB. In addition, hsa_circ_0001380 was found to be resistant to RNase R treatment. Moreover, four N6­adenosine methylation modification sites and two potential microRNA binding sites were predicted in silico. Importantly, the area under the ROC curve was 0.9502, which suggested that hsa_circ_0001380 may act as a diagnostic biomarker for APTB. Taken together, the results indicated that circRNA hsa_circ_0001380 was downregulated in the peripheral blood of patients with APTB, and could serve as a diagnostic biomarker.

BTLA-Expressing Dendritic Cells in Patients With Tuberculosis Exhibit Reduced Production of IL-12/IFN-α and Increased Production of IL-4 and TGF-ß, Favoring Th2 and Foxp3+ Treg Polarization.

Little is known about how tuberculosis (TB) impairs dendritic cell (DC) function and anti-TB immune responses. We previously showed that the B and T lymphocyte attenuator (BTLA), an immune inhibitory receptor, is involved in TB pathogenesis. Here, we examined whether BTLA expression in TB affects phenotypic and functional aspects of DCs. Active TB patients exhibited higher expression of BTLA in myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) subsets compared with healthy controls (HCs). BTLA expression was similarly high in untreated TB, TB relapse, and sputum-bacillus positive TB, but anti-TB therapy reduced TB-driven increases in frequencies of BTLA+ DCs. BTLA+ DCs in active TB showed decreased expression of the DC maturation marker CD83, with an increased expression of CCR7 in mDCs. BTLA+ DCs in active TB displayed a decreased ability to express HLA-DR and to uptake foreign antigen, with a reduced expression of the co-stimulatory molecule CD80, but not CD86. Functionally, BTLA+ DCs in active TB showed a decreased production of IL-12 and IFN-α as well as a reduced ability to stimulate allogeneic T-cell proliferative responses. BTLA+ mDCs produced larger amounts of IL-4 and TGF-ß than BTLA- mDCs in both HCs and APT patients. BTLA+ DCs from active TB patients showed a reduced ability to stimulate Mtb antigen-driven Th17 and Th22 polarizations as compared to those from HCs. Conversely, these BTLA+ DCs more readily promoted the differentiation of T regulatory cells (Treg) and Th2 than those from HCs. These findings suggest that TB-driven BTLA expression in DCs impairs the expression of functional DC surrogate markers and suppress the ability of DCs to induce anti-TB Th17 and Th22 response while promoting Th2 and Foxp3+ Tregs.

The Use of Customised Surgical Guide for Bilateral Inferior Mandibulectomy in a Case of Monostotic Fibrous Dysplasia

@#Fibrous dysplasia (FD) is a benign pathological condition of bone in which normal cancellous bone is replaced by immature woven bone and fibrous tissue. Surgical recontouring aims to remove the excess fibrous bone and achieve acceptable symmetry. Conventional surgery which depends on visual exposure and the surgeon’s assessment during the procedure poses a great challenge in obtaining a predictable surgical outcome especially in bilateral presentation. Recent advances in surgical technology may overcome this challenge. Herein, we present a case of 23 years old Chinese lady who underwent bilateral inferior mandibulectomy for monostotic fibrous dysplasia. The aims of this surgery were to recontour the mandible symmetrically via extraoral approach while preserving the inferior alveolar nerves and mental nerves with the aid of a surgical guide. A stereolithography model of the patient’s mandible was produced using the computed tomography (CT) scan data in Digital Imaging and Communications in Medicine (DICOM) format to assist in the surgery. Simulation with SurgiCase software (Materialise, Leuven, Belgium) was utilised in creating the customised surgical guide. The autoclavable surgical guide was manufactured by rapid prototyping technology and used intraoperatively to define the osteotomy line for mandibular recontouring. Virtual surgical planning greatly assists surgeons to deliver a good surgical result.

MTB driven B cells producing IL-35 and secreting high level of IL-10 in the patients with active pulmonary tuberculosis.

Regulatory B cells (Bregs) have critical roles as a negative regulator of immunity, mainly due to the fact that it secrets high a level of interleukin 10 (IL-10). Recently, a new subset of Bregs was identified as a key source of IL-35, which is an immunosuppressive cytokine and conventionally thought to be secreted by regulatory T cells (Tregs). Our previous study showed that the level of IL-35 in serum was elevated in the patients with active tuberculosis (ATB). However, none of the studies reported that IL-35 is secreted by B cells in ATB patients. In the current study, we found that the mRNA expressions of the both subunits (p35 and Ebi3) of IL-35 by circulating B cells were increased in ATB patients. By using immunohistochemistry and immunofluorescence staining, we found a subset of B cells infiltrated into the tuberculous granuloma of ATB patients also expressed IL-35. Moreover, Mycobacterium tuberculosis (MTB) lysate stimulation assay also demonstrated higher levels of IL-35 were exerted by MTB lysate within purified B cells from healthy control group (HC). Flow cytometry analysis further showed that the IL-35-producing B cells from ATB patients produced a higher level of IL-10. Taken together, IL-35-producing B cells may play a regulatory role during MTB infection by producing IL-10.