Dendritic cell SIRPα regulates homeostasis of dendritic cells in lymphoid organs

Signal regulatory protein α (SIRPα), an immunoglobulin superfamily protein that is expressed predominantly in myeloid lineage cells such as dendritic cells (DCs) or macrophages, mediates cell–cell signaling. In the immune system, SIRPα is thought to be important for homeostasis of DCs, but it remains unclear whether SIRPα intrinsic to DCs is indeed indispensable for such functional role. Thus, we here generated the mice, in which SIRPα was specifically ablated in CD11c⁺ DCs (Sirpa^ΔDC). Sirpa^ΔDC mice manifested a marked reduction of CD4⁺ CD8α^– conventional DCs (cDCs) in the secondary lymphoid organs, as well as of Langerhans cells in the epidermis. Such reduction of cDCs in Sirpa^ΔDC mice was comparable to that apparent with the mice, in which SIRPα was systemically ablated. Expression of SIRPα in DCs was well correlated with that of either endothelial cell‐selective adhesion molecule (ESAM) or Epstein–Barr virus‐induced molecule 2 (EBI2), both of which were also implicated in the regulation of DC homeostasis. Indeed, ESAM⁺ or EBI2⁺ cDCs were markedly reduced in the spleen of Sirpa^ΔDC mice. Thus, our results suggest that SIRPα intrinsic to CD11c⁺ DCs is essential for homeostasis of cDCs in the secondary lymphoid organs and skin.     

SIRPα on CD11c+ cells induces Th17 cell differentiation and subsequent inflammation in the CNS in experimental autoimmune encephalomyelitis

Signal regulatory protein α (SIRPα) is expressed predominantly on type 2 conventional dendritic cells (cDC2s) and macrophages. We previously showed that mice systemically lacking SIRPα were resistant to experimental autoimmune encephalomyelitis (EAE). Here, we showed that deletion of SIRPα in CD11c⁺ cells of mice (Sirpa^ΔDC mice) also markedly ameliorated the development of EAE. The frequency of cDCs and migratory DCs (mDCs), as well as that of Th17 cells, were significantly reduced in draining lymph nodes of Sirpa^ΔDC mice at the onset of EAE. In addition, we found the marked reduction in the number of Th17 cells and DCs in the CNS of Sirpa^ΔDC mice at the peak of EAE. Whereas inducible systemic ablation of SIRPα before the induction of EAE prevented disease development, that after EAE onset did not ameliorate the clinical signs of disease. We also found that EAE development was partially attenuated in mice with CD11c⁺ cell-specific ablation of CD47, a ligand of SIRPα. Collectively, our results suggest that SIRPα expressed on CD11c⁺ cells, such as cDC2s and mDCs, is indispensable for the development of EAE, being required for the priming of self-reactive Th17 cells in the periphery as well as for the inflammation in the CNS.     

Promotion of dermal regeneration using pullulan/gelatin porous skin substitute

Tissue‐engineered dermal substitutes represent a promising approach to improve wound healing and provide more sufficient regeneration, compared with current clinical standards on care of large wounds, early excision, and grafting of autografts. However, inadequate regenerative capacity, impaired regeneration/degradation profile, and high cost of current commercial tissue‐engineered dermal regeneration templates hinder their utilization, and the development of an efficient and cost‐effective tissue‐engineered dermal substitute remains a challenge. Inspired from our previously reported data on a pullulan/gelatin scaffold, here we present a new generation of a porous pullulan/gelatin scaffold (PG2) served as a dermal substitute with enhanced chemical and structural characteristics. PG2 shows excellent biocompatibility (viability, migration, and proliferation), assessed by in vitro incorporation of human dermal fibroblasts in comparison with the Integra® dermal regeneration template (Control). When applied on a mouse full‐thickness excisional wound, PG2 shows rapid scaffold degradation, more granulation tissue, more collagen deposition, and more cellularity in comparison with Control at 20 days post surgery. The faster degradation is likely due to the enhanced recruitment of inflammatory macrophages to the scaffold from the wound bed, and that leads to earlier maturation of granulation tissue with less myofibroblastic cells. Collectively, our data reveal PG2's characteristics as an applicable dermal substitute with excellent dermal regeneration, which may attenuate scar formation.     

Potential Health Benefits of Curcumin on Female Reproductive Disorders: A Review

Curcumin is one of the main polyphenolic compounds in the turmeric rhizome. It possesses antioxidant, anti-inflammatory, anti-cancer, anti-arthritis, anti-asthmatic, anti-microbial, anti-viral and anti-fungal properties. This review aims to provide an overview of the potential health benefits of curcumin to treat female reproductive disorders, including polycystic ovary syndrome (PCOS), ovarian failure and endometriosis. Comprehensive information on curcumin was retrieved from electronic databases, which were MEDLINE via EBSCOhost, Scopus and Google Scholar. The available evidence showed that curcumin reduced the high level of androgen in PCOS. Studies in rodents suggest that curcumin resulted in the disappearance of cysts and the appearance of healthy follicles and corpora lutea. Furthermore, animal studies showed curcumin improved the overall function of the ovary in ovarian diseases and reversed the disturbance in oxidative stress parameters. Meanwhile, in vitro and in vivo studies reported the positive effects of curcumin in alleviating endometriosis through anti-inflammatory, anti-proliferative, anti-angiogenic and pro-apoptotic mechanisms. Thus, curcumin possesses various effects on PCOS, ovarian diseases and endometriosis. Some studies found considerable therapeutic effects, whereas others found no effect. However, none of the investigations found curcumin to be harmful. Curcumin clinical trials in endometriosis and ovarian illness are still scarce; thus, future studies need to be conducted to confirm the safety and efficacy of curcumin before it could be offered as a complementary therapy agent.     

Neurofibromatosis type 2 gene mutation and progesterone receptor messenger RNA expression in the pathogenesis of sporadic orbitocranial meningioma

AIM: To investigate neurofibromatosis type 2 (NF2) gene mutation at mRNA levels in sporadic orbitocranial meningioma and its association with progesterone receptor (PR) mRNA expression. METHODS: This was a case-control study. Thirty-four sporadic meningioma patients with no familial NF2-related meningioma history were recruited. They were interviewed for their obstetric, gynecologic, and contraception history. PR investigation was performed with real-time polymerase chain reaction (PCR). NF2 mutation was investigated using Qbiomarker Somatic Mutation PCR Assay at NF2 mRNA level after its cDNA extraction (four mRNA mutation cytoband coordinates for nucleotide change: c.634C>T/p.Q212, c.655G>A/p.V219M, c.784C>T/p.R262 and c.1228C>T/p. Q410). RESULTS: After mutation analysis at mRNA level, NF2 gene mutation was found in 35.29% patients. Non-mutation group was strongly associated with exogenous hormonal exposure (non-mutation vs mutation: 95.5% vs 83.3%, P<0.001). PR mRNA was found significantly lower in non-mutation group (P=0.033) which presumed as long term exogenous progesterone exposure. However, mutation group was associated with higher rate of progression to grade II (mutation vs non-mutation, 18.2% vs 5%, P<0.001) and was associated more in fibrous and anaplastic tumor tissue. CONCLUSION: NF2 mutation-meningioma is associated with higher grade of meningioma. Non NF2 mutation-meningioma is strongly associated with exogenous progesterone exposure and lower PR expression.     

SIRPα+ dendritic cells promote the development of fibroblastic reticular cells in murine peripheral lymph nodes

Nonhematopoietic stromal cells contribute to the organization and homeostasis of secondary lymphoid organs by producing cytokines and chemokines. The development and maintenance of these stromal cells are thought to be regulated by innate immune cells. Indeed, we recently showed that signal regulatory protein α (SIRPα)‐positive dendritic cells (DCs) are essential for the proliferation and survival of podoplanin (Pdpn)‐positive fibroblastic reticular cells (FRCs) in mouse spleen. We have now established an in vitro culture system for lymph node stromal cells (LNSCs) isolated from mouse peripheral LNs. Activated DCs and TNF‐α each promoted the proliferation of cultured LNSCs, most of which were found to be Pdpn⁺ FRCs. Furthermore, ablation of SIRPα in CD11c⁺ cells attenuated this effect of DCs on LNSC proliferation. Transplantation of activated DCs together with cultured LNSCs into the renal subcapsular space markedly increased the number of ER‐TR7⁺ stromal cells as well as induced the accumulation of T cells and increased the expression of Ccl19 in the transplants. Ablation of SIRPα in CD11c⁺ cells greatly impaired the development of LN‐like structure in the transplants. Our findings thus suggest that SIRPα⁺ DCs are important for the proliferation and differentiation of Pdpn⁺ FRCs in peripheral LNs.     

Multiple regions of absent bone mineral and marrow function in a patient with chronic renal failure.

99mTc-methylene diphosphonate bone mineral and 99mTc-sulfur colloid bone marrow studies were performed on a patient with chronic renal failure. Multiple regions of absent deposition of both radiotracers were noted, involving the right ilium, multiple ribs, and the manubrium. Radiographs of these bones were normal. The findings suggest absent regional perfusion of the involved bones.     

Lag time, high-risk histopathological features, metastasis, and survival interrelation in retinoblastoma: a perspective from lower-middle income country

AIM: To investigate the impact of lag time to metastasis and survival rates among patients with retinoblastoma. METHODS: This retrospective study was conducted with 52 patients from the Department of Ophthalmology and the Department of Pediatrics of Dr. Sardjito General Hospital, between 1st January 2014 and 31st December 2020. Lag time was defined as the time delay between the first sign of retinoblastoma to the diagnosis of retinoblastoma. The subjects with lag time > one year were included in the case group, while the subjects with lag time < one year were included in the control group. RESULTS: The lag time was significantly correlated with American Joint Committee on Cancer and Intraocular Classification of Retinoblastoma staging of retinoblastoma (P=0.005 and P=0.006, respectively). The lag time was also significantly correlated with both metastasis event [odds ratio (OR): 5.06, 95%Cl: 1.56-16.44, P=0.006] and mortality (OR: 4.54, 95%Cl: 1.37-15.07, P=0.011). The follow-up was continued for 32 subjects for 3y after initial diagnoses. Survival analysis revealed a significant difference among these two groups (P=0.021). Furthermore, lag time was significantly correlated with survival of retinoblastoma (r=-0.53, P=0.046). CONCLUSION: The study highlights the importance of lag time between the onset of first symptoms and the time of retinoblastoma diagnosis which significantly contribute to metastasis and mortality of patients with retinoblastoma. Examinations for the early detection of retinoblastoma should be performed for individuals at-risk to minimize lag time and improve the outcomes.     

产后抑郁症的社区护理干预研究

目的:探讨产后抑郁症的社区护理干预.方法:定性与定量研究相结合,定性研究采用专题小组讨论和半结构性访谈,产妇9人参加专题讨论,半结构性访谈12人;定量研究随机抽取本市各社区产后42d左右的产妇200例问卷调查.结果:产妇"月子"期间常发生头疼、恶心、焦虑、恐惧、失眠以及照顾新生儿困难;半结构性访谈中有1产妇处于产后抑郁症的临界,EPDS量表测定为12分;173例"月子"里有身心健康问题的产妇中,求助者91.3%,其中需要社区护理人员帮助的64.2%,但实际寻求帮助的只有13.9%.结论:实施产后抑郁症的社区护理干预,应针对产妇"月子"期间的身心健康问题提供护理支持与指导,做到预防为主.与此同时,应加强社区护理人员培训、强化社区服务的规范化管理.     

Renal uptake of 99mTc-sulfur colloid in congestive heart failure

Renal uptake of 99mTc-sulfur colloid during liver and spleen imaging was observed in 4 patients; all had moderate to severe congestive heart failure. Four similar patients with this association have been reported. Although the exact mechanism of colloid uptake by the kidneys is not known, an association with congestive heart failure seems likely.