Type 2 innate lymphoid cells (ILC2s, nuocytes, NHC) require RORA and GATA3 for their development. We show that human ILC2s express skin homing receptors and infiltrate the skin after allergen ...challenge, where they produce the type 2 cytokines IL-5 and IL-13. Skin-derived ILC2s express the IL-33 receptor ST2, which is up-regulated during activation, and are enriched in lesional skin biopsies from atopic patients. Signaling via IL-33 induces type 2 cytokine and amphiregulin expression, and increases ILC2 migration. Furthermore, we demonstrate that E-cadherin ligation on human ILC2 dramatically inhibits IL-5 and IL-13 production. Interestingly, down-regulation of E-cadherin is characteristic of filaggrin insufficiency, a cardinal feature of atopic dermatitis (AD). ILC2 may contribute to increases in type 2 cytokine production in the absence of the suppressive E-cadherin ligation through this novel mechanism of barrier sensing. Using Rag1(-/-) and RORα-deficient mice, we confirm that ILC2s are present in mouse skin and promote AD-like inflammation. IL-25 and IL-33 are the predominant ILC2-inducing cytokines in this model. The presence of ILC2s in skin, and their production of type 2 cytokines in response to IL-33, identifies a role for ILC2s in the pathogenesis of cutaneous atopic disease.
The occurrence of dengue haemorrhagic fever (DHF) is thought to result from a complex interplay between the virus, host genetics and host immune factors. Existing published data are not consistent, ...in part related to relatively small sample sizes. We set out to determine possible associations between dengue virus (DEN-V) NS3 specific T cells and cytokine and chemokine levels and the pathogenesis of severe disease in a large cohort of individuals with DHF.
By using ex vivo IFNγ ELISpot assays we determined DENV-NS3 specific responses in patients with varying severity of DHF. Other cytokines produced by DENV-NS3 specific T cells were determined by using multiple bead array analysis (MBAA). We also determined the serum cytokine levels using MBAA, lymphocyte subsets and Annexin V expression of lymphocytes in patients with varying severity of DHF. Of the 112 DHF patients studied, 29 developed shock. Serum IL-10 and IP-10 levels positively and significantly correlated with T cell apoptosis while IL-10 levels inversely correlated with T cell numbers. In contrast, TGFß showed a very significant (P<0.0001) and positive correlation (Spearman's R = 0.65) with the platelet counts, consistent with platelet release. We found that whilst patients with severe dengue had lower total T cell numbers, the DV-NS3 specific T cells persisted and produced high levels of IFNγ but not TNFα, IL-3, IL-13, IL-2, IL-10 or IL-17.
Our data suggest that serum IL-10, TNFα and TGFβ differentially associate with dengue disease severity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We conducted Passerini-type multicomponent polymerizations (P-MCPs) with various monomers and afforded a series of functional poly(carbamoyl ester)s (PCEs). We demonstrated an efficient, diverse, and ...facile approach through P-MCPs to produce these novel PCEs with dual-cleavable linkages of ester and disulfide groups and the aggregation-induced emission (AIE) luminogen tetraphenylethylene (TPE).
Our group have demonstrated that splenic B cells contributed to the CD4+CD25− naive T cells conversion into CD4+CD25+Foxp3− regulatory T cells without adding appended cytokines, named Treg‐of‐B cells ...which were potent suppressors of adaptive immunity. We like to investigate whether Treg‐of‐B cells could promote alternatively activated macrophage (M2 macrophages) polarization and alleviate inflammatory disease, psoriasis. In this study, we co‐cultured the bone marrow‐derived macrophages (BMDMs) with Treg‐of‐B cells under LPS/IFN‐γ stimulation and analyzed the M2‐associated gene and protein using qPCR, western blotting, and immunofluorescence staining. We also examined the therapeutic effect of Treg‐of‐B cell‐induced M2 macrophage for skin inflammation using imiquimod (IMQ)‐induced psoriatic mouse model. Our results showed that BMDMs co‐cultured with Treg‐of‐B cells upregulated typical M2‐associated molecules, including Arg‐1, IL‐10, Pdcd1lg2, MGL‐1, IL‐4, YM1/2 and CD206. In an inflammatory environment, TNF‐α and IL‐6 production by macrophages co‐cultured with Treg‐of‐B cells was decreased significantly. The molecular mechanism revealed that Treg‐of‐B cells promoted M2 macrophage polarization via STAT6 activation in a cell contact‐dependent manner. Moreover, the treatment with Treg‐of‐B cell‐induced M2 macrophages attenuated the clinical manifestations of psoriasis, such as scaling, erythema and thickening in the IMQ‐induced psoriatic mouse model. T cell activation in draining lymph nodes was decreased in the Treg‐of‐B cell‐induced M2 macrophage group after IMQ application. In conclusion, our findings suggested that Foxp3− Treg‐of‐B cells could induce alternatively activated M2 macrophages through STAT6 activation, providing a cell‐based therapeutic strategy for psoriasis.
Background
Atopic dermatitis (AD) occurs in exclusively breastfed infants. As fatty acids have some immunomodulatory effect, we aimed to investigate the influence of fatty acid compositions in breast ...milk (BM) on the development of AD in exclusively breastfed infants.
Methods
We enrolled two‐ to four‐month‐old exclusively breastfed infants. The objective SCORing Atopic Dermatitis (objSCORAD) was evaluated. The lipid layer of BM was analyzed by gas chromatography for fatty acid levels. Medical charts were reviewed.
Results
Forty‐seven AD infants and 47 healthy controls were enrolled. The objSCORAD was 20.5 ± 1.7 (shown as mean ± SEM) in the AD group. The age, sex, parental atopy history, and nutrient intake of mothers were not significantly different between two groups. The palmitate and monounsaturated fatty acid (MUFA) levels in BM positively correlated with objSCORAD, while caprylate, acetate, and short‐chain fatty acid (SCFA) levels negatively correlated with objSCORAD (p = .031, .019, .039, .013, .022, respectively). However, the butyrate levels in BM were not significantly different. The caprylate and acetate levels in BM were significantly associated with the presence of infantile AD (p = .021 and .015, respectively) after adjusting for age, sex, parental allergy history, MUFA, palmitate, and SCFA levels in BM. ObjSCORAD in infancy was significantly associated with persistent AD (p = .026) after adjusting for age, sex, parental atopy history, caprylate, palmitate, MUFA, acetate, and SCFA levels in BM.
Conclusion
Caprylate and acetate levels in BM for exclusively breastfed infants were negatively associated with objSCORAD. Lower caprylate and acetate in BM might be the risk factors for infantile AD, while butyrate in BM was not associated with infantile AD.
Background
Our previous study showed that the discontinuation of breastfeeding could improve atopic dermatitis (AD) symptoms in exclusively breastfed infants. As vitamins A and D are influential on ...the immune system, we aimed to analyze the association of vitamin A and D levels in breast milk (BM) with AD.
Methods
We enrolled two‐ to four‐month‐old exclusively breastfed infants. The objective SCORing Atopic Dermatitis (objSCORAD) was evaluated. The lipid layer of BM was extracted and analyzed by liquid chromatography for vitamin A and D levels. Medical charts were reviewed for the clinical course of AD.
Results
Forty‐five AD patients and 45 healthy controls were enrolled. The objSCORAD was 20.54 ± 1.73 (shown as mean ± SEM) in the AD group. The sex, parental atopy history, nutrient intake of mothers, and vitamin A levels in BM were not significantly different between the two groups. The 25‐(OH) D3 level in BM was significantly lower in the AD group than in the control group (1.72 ± 0.30 and 3.95 ± 0.64 ng/mL, respectively; P = .001). The 25‐(OH) D3 level negatively correlated with objSCORAD (P = .003). The only factor that is significantly associated with persistent AD is the objSCORAD in infancy (P = .003) after adjusting for age, sex, parental atopy history, and 25‐(OH) D3 level by multiple regression.
Conclusion
Vitamin D levels in BM for exclusively breastfed infants were negatively associated with objSCORAD. Lower vitamin D levels in BM might be a risk factor for infantile AD.
Scope
Curcumin, a potent antioxidant extracted from Curcuma longa, confers protection against atherosclerosis, yet the detailed mechanisms are not fully understood. In this study, we examined the ...effect of curcumin on lipid accumulation and the underlying molecular mechanisms in macrophages and apolipoprotein E‐deficient (apoE−/−) mice.
Methods and results
Treatment with curcumin markedly ameliorated oxidized low‐density lipoprotein (oxLDL)‐induced cholesterol accumulation in macrophages, which was due to decreased oxLDL uptake and increased cholesterol efflux. In addition, curcumin decreased the protein expression of scavenger receptor class A (SR‐A) but increased that of ATP‐binding cassette transporter (ABC) A1 and had no effect on the protein expression of CD36, class B receptor type I (SR‐BI), or ATP‐binding cassette transporter G1 (ABCG1). The downregulation of SR‐A by curcumin was via ubiquitin–proteasome–calpain‐mediated proteolysis. Furthermore, the curcumin‐induced upregulation of ABCA1 was mainly through calmodulin‐liver X receptor α (LXRα)‐dependent transcriptional regulation. Curcumin administration modulated the expression of SR‐A, ABCA1, ABCG1, and SR‐BI in aortas and retarded atherosclerosis in apoE−/− mice.
Conclusion
Our findings suggest that inhibition of SR‐A‐mediated oxLDL uptake and promotion of ABCA1‐dependent cholesterol efflux are two crucial events in suppression of cholesterol accumulation by curcumin in the transformation of macrophage foam cells.
Abstract
Background
Previous works reported people with schizophrenia experienced inferior hand functions which influence their daily participation and work efficiency. Sensorimotor capability is one ...of indispensable elements acting in a well-executed feed-forward and feedback control loop to contribute to hand performances. However, rare studies investigated contribution of sensorimotor ability to hand functions for people with schizophrenia. This study aimed to explore hand function in people with schizophrenia based on the perspective of the sensorimotor control capabilities of the hands.
Methods
Twenty-seven people at the chronic stage of schizophrenia were enrolled. The following assessment tools were used: the Purdue Pegboard Test (PPT) and the VALPAR Component Work Sample-8 (VCWS 8) system for hand function; the Self-Reported Graphic version of the Personal and Social Performance (SRG-PSP) scale for functionality; and the Semmes-Weinstein Monofilaments (SWM), the pinch-holding-up-activity (PHUA) test and the Manual Tactile Test (MTT) for the sensory and sensorimotor parameters. The Clinical Global Impression-Severity (CGI-S) scale and the Extrapyramidal Symptom Rating Scale (ESRS) were used to grade the severity of the illness and the side-effects of the drugs. Spearman’s rank correlation coefficient was used to analyze associations among hand function, functionality, and sensorimotor capabilities. A multiple linear regression analysis was used to identify the determinants of hand function.
Results
The results indicated that both hand function and sensorimotor capability were worse in people with schizophrenia than in healthy people, with the exception of the sensory threshold measured with the SWM. Moreover, the sensorimotor abilities of the hands were associated with hand function. The results of the regression analysis showed that the MTT measure of stereognosis was a determinant of the PPT measure of the dominant hand function and of the performance on the VCWS 8, and that the ESRS and the MTT measure of barognosis were determinants of the performance on the assembly task of the PPT.
Conclusions
The findings suggested that sensorimotor capabilities, especially stereognosis and barognosis, are crucial determinants of hand function in people with schizophrenia. The results also revealed that the side effects of drugs and the duration of the illness directly affect hand function.
Clinical Trail Registration
ClinicalTrials.gov
, identifier NCT04941677, 28/06/2021.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective: Injuries to the hands, wrists, and fingers often involve damage to the tendons. The ability to measure tendon movements during the rehabilitation process can provide clinicians with ...important information in the quantification of tendon injuries. Conventionally, the tendon is considered a single spring-like structure during force transmission, and its twisted structure is neglected. Recently, clinicians believed that the twisted fiber structure (which enables tendon rotation during movement) of the tendon can provide it with a degree of elasticity and improve the efficiency of force transmission. However, observation of the hand tendon rotation in vivo by using the current imaging modalities is difficult. Methods: In this study, a 40-MHz high-frequency vector Doppler imaging (HFVDI) was used to visualize the movement of the hand tendon during muscle contraction. The performance of HFVDI was verified using a rotation phantom experiment. Two human experiments were designed in the present study: 1) participants were allowed to bend their distal and proximal interphalangeal (DIP and PIP) joints of fingers freely and 2) the PIP joint of the finger was fixed such that only the DIP could be moved. The HFVDIs of the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) tendons were obtained in the transverse and longitudinal views to observe the movements of the hand tendon during finger movements. Results: The average longitudinal displacements of the FDS and FDP were approximately 3-4 mm for free bending of the finger; however, it was reduced when only the DIP was moved. The rotational phenomenon of the FDS and FDP tendons was observed in the transverse view, which demonstrated the different rotational behaviors of the FDS and FDP fibers during muscle contraction. Conclusion: All the results validated the potential of HFVDI as a novel tool for visualizing tendon rotation and would be useful in providing quantitative information regarding tendon function to determine the rehabilitation process following injuries.
In this study we performed atom transfer radical polyadditions (ATRPAs) of the inimer 4-vinylbenzyl 2-bromo-2-phenylacetate (VBBPA), catalysed by environmentally friendly FeX
3
/triphenylphosphine ...(TPP) complexes in the absence of a reducing agent. Interestingly, we obtained linear-type PVBBPA polyesters of high molecular weight (MW) (
M
w
=
ca.
27 000;
M
w
/
M
n
(
) = 1.50). UV-Vis spectroscopy revealed that reduction of the Fe
III
complex to an Fe
II
complex was mediated by the VBBPA inimer, such that we could regard the mechanism as a generation of activators by inimer addition (GAIMA) ATRPA. In the presence of reducing agents, Fe
0
and proanthocyanidins (PC), the chain branching reaction occurred at 70 °C, possibly because of insufficient deactivation from the deactivator to the benzylic radical (PhCH
2
&z.rad;) at the polymer backbone. At a moderate reaction temperature and in the presence of a moderate amount of Fe
0
, a high-MW PVBBPA polyester was obtained (
M
w
=
ca.
40 000;
= 2.40). The PVBBPAs were then subjected to successive quantitative azidation and copper(
i
)-catalysed azide/alkyne cycloaddition (CuAAC) click reactions to obtain amphiphilic polymer brushes (APBs). By clicking different ratios of oligo(ethylene glycol)
n
(OEG
n
-&z.tbd;;
n
= 4, 7, 12) and 1-octyne (Oct), we observed reversible cloud points in the approximate range of 40-65 °C for the (OEG
7
/Oct)- and (OEG
12
/Oct)-grafted APBs; in contrast, only aggregation occurred for the (OEG
4
/Oct)-grafted APBs. The sizes of the micellized APBs were in the approximate range of 50-90 nm. We examined the drug release behavior of these APBs toward rhodamine B, as a model compound. The release profiles revealed high degrees of release (
ca.
70-80%) in acidic environments, but they were poor (<10%) in neutral solutions, suggesting pH-sensitive behavior that resulted from the triazole units positioned along the polymer backbone.
Novel aliphatic polyesters were synthesized and quantitatively modified by click reactions to obtain amphiphilic polymer brushes for nano-carrier applications.
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