Narrowing the focus: Therapeutic cell surface targets for refractory triple-negative breast cancer

Triple-negative breast cancer (TNBC) is defined as a type of breast cancer with lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor 2 protein. In comparison to other types of breast cancer, TNBC characterizes for its aggressive behavior, more prone to early recurrence and a disease with poor response to molecular target therapy. Although TNBC is identified in only 25%-30% of American breast cancer cases annually, these tumors continue to be a therapeutic challenge for clinicians for several reasons: Tumor heterogeneity, limited and toxic systemic therapy options, and often resistance to current standard therapy, characterized by progressive disease on treatment, residual tumor after cytotoxic chemotherapy, and early recurrence after complete surgical excision. Cell-surface targeted therapies have been successful for breast cancer in general, however there are currently no approved cell-surface targeted therapies specifically indicated for TNBC. Recently, several cell-surface targets have been identified as candidates for treatment of TNBC and associated targeted therapies are in development. The purpose of this work is to review the current clinical challenges posed by TNBC, the therapeutic approaches currently in use, and provide an overview of developing cell surface targeting approaches to improve outcomes for treatment resistant TNBC.     

探析新型冠状病毒肺炎的眼表损害及中西医治疗对策＊

新型冠状病毒肺炎（corona virus disease 2019，COVID-19）自2019年12月爆发以来，由于具有高传染性，迅速在世界各地蔓延，国内外疫情防治形势空前严峻。COVID-19不仅造成肺部、肠道、肾脏等多脏器损害，且部分患者以眼表损害为首发或伴发症状出现，临床上很容易被忽视。COVID-19的眼表损害归属于祖国医学“天行赤眼”范畴，本文结合国内外最新的文献报道，探讨新型冠状病毒（2019 novel corona virus，2019-nCoV）对眼表的损害，阐明其可能机制，并从中西医角度提出可行的治疗措施。     

Ultrasound-Assist Extrusion Methods for the Fabrication of Polymer Nanocomposites Based on Polypropylene/Multi-Wall Carbon Nanotubes

Isotactic polypropylenes (iPP) with different melt flow indexes (MFI) were used to fabricate nanocomposites (NCs) with 10 wt % loadings of multi-wall carbon nanotubes (MWCNTs) using ultrasound-assisted extrusion methods to determine their effect on the morphology, melt flow, and electrical properties of the NCs. Three different types of iPPs were used with MFIs of 2.5, 34 and 1200 g/10 min. Four different NC fabrication methods based on melt extrusion were used. In the first method melt extrusion fabrication without ultrasound assistance was used. In the second and third methods, an ultrasound probe attached to a hot chamber located at the exit of the die was used to subject the sample to fixed frequency and variable frequency, respectively. The fourth method is similar to the first method, with the difference being that the carbon nanotubes were treated in a fluidized air-bed with an ultrasound probe before being used in the fabrication of the NCs with no ultrasound assistance during extrusion. The samples were characterized by MFI, Optical microscopy (OM), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), electrical surface resistivity, and electric charge. MFI decreases in all cases with addition of MWCNTs with the largest decrease observed for samples with the highest MFI. The surface resistivity, which ranged from 10¹³ to 10⁵ Ω/sq, and electric charge, were observed to depend on the ultrasound-assisted fabrication method as well as on the melt flow index of the iPP. A relationship between agglomerate size and area ratio with electric charge was found. Several trends in the overall data were identified and are discussed in terms of MFI and the different fabrication methods.     

The effect of Benson’s relaxation response on sleep quality and anorexia in cancer patients undergoing chemotherapy: A randomized controlled trial

Background and objectivesPatients with cancer experience many side effects due to its nature and usual treatments. Sleep disorders and anorexia are the most commonly reported symptoms in cancer patients undergoing chemotherapy. The present study aimed to investigate the effect of Benson's Relaxation Response (BRR) on sleep quality and anorexia in cancer patients undergoing chemotherapy.Methodology and participantsIn the present clinical trial, a total of 84 patients were enrolled and randomly divided into two groups of experimental and control. Benson's relaxation response was administered to the experimental group twice a day over 5 consecutive days. Data was collected using St. Mary's Hospital Sleep Questionnaire (SMHSQ) and anorexia questionnaire with Visual Analog Scale (VAS).ResultsThe results of our study showed a significant improvement in the sleep quality in the experimental group at 24 (p = 0.02) and 48 (p = 0.001) hours after the intervention compared to the control group. Benson's relaxation response (BRR) also had a significant effect on the anorexia in the experimental group at 24 (7.5 ± 1.6) and 48 (6.9 ± 2.1) hours after the intervention compared to the control group. No side effects were reported during the study and follow-up period.ConclusionBenson's relaxation response as a complementary method may improve sleep quality and anorexia in cancer patients undergoing chemotherapy. Further studies with greater sample size and longer follow-up period are needed to confirm the current findings.     

Decellularized porcine conjunctiva as an alternative substrate for tissue-engineered epithelialized conjunctiva

PurposeThe long-term success of visual rehabilitation in patients with severe conjunctival scarring is reliant on the reconstruction of the conjunctiva with a suitable substitute. The purpose of this study is the development and investigation of a re-epithelialized conjunctival substitute based on porcine decellularized conjunctiva (PDC).MethodsPDC was re-epithelialized either with pre-expanded human conjunctival epithelial cells (PDC + HCEC) or with a human conjunctival explant placed directly on PDC (PDC + HCEx). Histology and immunohistochemistry were performed to evaluate epithelial thickness, proliferation (Ki67), apoptosis (Caspase 3), goblet cells (MUC5AC), and progenitor cells (CK15, ΔNp63, ABCG2). The superior construct (PDC + HCEx) was transplanted into a conjunctival defect of a rabbit (n = 6). Lissamine green staining verified the epithelialization in vivo. Orbital tissue was exenterated on day 10 and processed for histological and immunohistochemical analysis to examine the engrafted PDC + HCEx. A human-specific antibody was used to detect the transplanted cells.ResultsFrom day-14 in vitro onward, a significantly thicker epithelium and greater number of cells expressing Ki67, CK15, ΔNp63, and ABCG2 were noted for PDC + HCEx versus PDC + HCEC. MUC5AC-positive cells were found only in PDC + HCEx. The PDC + HCEx-grafted rabbit conjunctivas were lissamine-negative during the evaluation period, indicating epithelial integrity. Engrafted PDC + HCEx showed preserved progenitor cell properties and an increased number of goblet cells comparable to those of native conjunctiva.ConclusionPlacing and culturing a human conjunctival explant directly on PDC (PDC + HCEx) enables the generation of a stable, stratified, goblet cell-rich construct that could provide a promising alternative conjunctival substitute for patients with extensive conjunctival stem and goblet cell loss.     

碘乙酸钠诱导的大鼠膝骨关节炎模型肠道菌群变化及其潜在影响

目的:研究碘乙酸钠诱导的大鼠膝骨关节炎(KOA)模型肠道菌群变化情况,探究肠道菌群与KOA的潜在联系。方法:将SPF级大鼠分为空白对照组和KOA组,通过膝关节局部注射碘乙酸钠制造大鼠KOA模型。通过16SrDNA检测大鼠粪便中的肠道菌群变化情况,蛋白印记法检测结肠组织中NF-κB和TNF-α蛋白表达,RT-qPCR检测结肠组织中Caspase-1和IL-1β基因表达情况,苏木精-伊红染色观察结肠黏膜通透性变化,苏木精-伊红染色观察关节滑膜和软骨组织的病理变化情况。ELISA检测血液上清中LBP,IL-1β,TNF-α及IL-10炎症因子水平。结果:与空白对照组相比,从KOA组中筛选出明显变化的肠道菌群,以Akkermansia和疣微菌门变化最为显著,结肠黏膜通透性增加,结肠组织中NF-κB p65及TNF-α蛋白表达升高,结肠组织中Caspase-1和IL-1β基因表达升高,血液中促炎因子LBP,IL-1β及TNF-α蛋白含量升高,抗炎因子IL-10蛋白含量降低。结论:KOA病理状态下肠道菌群发生变化,结肠炎症反应增强,结肠炎症反应或许在提高全身炎症反应水平、促进与肠道菌群相关的KOA的病理进程中起到重要的桥梁作用。     

Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.