Notes

Perseverance as well as healing of regressing 3-mm ovarian hair follicles inside heifers.
Myostatin (MSTN) and myogenic differentiation antigen (MyoD) play an essential role in specification and differentiation of skeletal muscle. However, the role of stress in the regulation of MyoD and MSTN has not been fully revealed and more evidence should be provided. Here, we reported the cloning and expressional analyses of MSTN and MyoD in Large-scale Loach Paramisgurnus dabryanus (hereafter PdMSTN and PdMyoD). Injecting individuals with 0, 60, 600, and 1,200 μg/kg dexamethasone (DXM) for five consecutive days resulted in a dose-dependent change of PdMSTN and PdMyoD expression. The expression of PdMSTN was upregulated with increasing DXM concentrations, while PdMyoD expression was downregulated. The changes in the expression of these genes at different time points for 10 consecutive days were studied after individuals were treated with 600 μg/kg DXM. #link# Compared with the control group, PdMSTN expression decreased and PdMyoD expression increased before 12 h, and both PdMSTN and PdMyoD expression levels increased at 24 h, which was significantly higher than those in control group. At a prolonged treatment of 5-10 d, expression levels of PdMSTN and PdMyoD had significantly reduced. The results indicate that both PdMyoD and PdMSTN are involved in DXM-induced stress in Large-scale Loach.Lead poisoning, mainly through incidental ingestion of lead ammunition in carcasses, is a threat to scavenging and predatory bird species worldwide. link2 In Australia, shooting for animal control is widespread, and a range of native scavenging species are susceptible to lead exposure. However, the prevalence of lead exposure in Australia's scavenging and predatory birds is largely unknown. We evaluated the degree to which the Tasmanian wedge-tailed eagle (Aquila audax fleayi), an endangered Australian raptor and facultative scavenger, showed evidence of lead exposure. read more detected lead in 100% of femur and liver tissues of 109 eagle carcasses opportunistically collected throughout Tasmania between 1996 and 2018. Concentrations were elevated in 10% of 106 liver (>6 mg/kg dry wt) and 4% of 108 femur (>10 mg/kg dry wt) samples. We also detected lead in 96% of blood samples taken from 24 live nestlings, with 8% at elevated concentrations (>10 μg/dL). Of the liver samples with elevated lead, 73% had lead207/206 isotope ratios within the published range of lead-based bullets available in Tasmania. These first comprehensive data on lead exposure of an Australian raptor are comparable to those for raptor studies elsewhere that identify lead-based ammunition exposure as a conservation threat. Our findings highlight the importance of further research and efforts to address lead contamination throughout the Tasmanian ecosystem and in other Australian regions. Environ Toxicol Chem 2021;40219-230. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab treatment in RRAL in real-world setting.

A retrospective multisite study of RRAL patients treated with daratumumab alone and in combinations.

Forty-nine patients, diagnosed between 1.1.2008 and 1.2.2018 were included; 27% also had multiple myeloma (MM). Revised Mayo score was≥3 in 67%. Hematologic overall response rate was 81%, 64% achieved very good partial response (VGPR) or better. Concurrent active MM was associated with lower rates of VGPR (OR 0.19, 95% CI 0.04-0.81; P=.03) in a multi-variate analysis. Cardiac and renal responses were 74% and 73%, respectively. Median progression-free survival (PFS) was 28.4months and median overall survival (OS) was not reached; 2-year PFS and OS were 68.6±7.5% and 90.4±4.6%, respectively. Hematologic response correlated with prolonged PFS and OS. link3 Daratumumab was safe and well tolerated, no patients discontinued therapy due to toxicity. Our data was aligned with outcomes from a systematic literature review, which identified 10 case series (n=517) and 2 clinical trials (n=62) meeting prespecified criteria.

Our data support favorable safety tolerability and efficacy of daratumumab among non-selective RRAL patients in a real-world setting.
Our data support favorable safety tolerability and efficacy of daratumumab among non-selective RRAL patients in a real-world setting.Iatrogenic nerve injury during surgery is a major source of concern for both patients and surgeons. This study aimed to identify the nerves most commonly injured during surgery, along with the commonly associated operative procedures. A literature search was conducted using the PubMed database to identify nerves commonly injured during surgery, along with the surgical procedure associated with the injury. The following 11 nerves, ranked in order with their associated surgical procedures, were found to be the most commonly injured (a) intercostobrachial nerve in axillary lymph node dissections and transaxillary breast augmentations, (b) vestibulocochlear nerve in cerebellopontine tumor resections and vestibular schwannoma removals, c) facial nerve in surgeries of the inner ear and cheek region, (d) long thoracic nerve in axillary lymph node dissections, (e) spinal accessory nerve in surgeries of the posterior triangle of the neck and cervical lymph node biopsies, (f) recurrent laryngeal nerve in thyroid surgeries, (g) genitofemoral nerve in inguinal hernia and varicocele surgeries, (h) sciatic nerve in acetabular fracture repairs and osteotomies, (i) median nerve in carpal tunnel release surgeries, (j) common fibular nerve in varicose vein and short saphenous vein surgeries, and (k) ulnar nerve in supracondylar fracture surgeries. Although the root cause of iatrogenic nerve injury differs for each nerve, there are four unifying factors that could potentially decrease this risk for all peripheral nerves. These four influencing factors include knowledge of potential anatomical variations, visual identification of at-risk nerves during the procedure, intraoperative nerve monitoring, and expertise of the surgeon.Emerging evidence suggests that miR-143 plays an important role in the regulation of tumor sensitivity to chemotherapeutic agents. The study explores the underlying mechanism of miR-143 in reversing cisplatin resistance in ovarian cancer. The cisplatin-resistant ovarian cancer cell line A2780/CDDP was induced and established via treating A2780 cells by gradually increasing cisplatin concentrations. The IC50 values of A2780/CDDP and A2780 to cisplatin were 218.10 ± 1.12 and 21.99 ± 1.12 μM, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed that miR-143 was significantly decreased in A2780/CDDP cells compared with A2780 cells. miR-143 overexpression decreased cisplatin resistance in A2780/CDDP, and miR-143 inhibition decreased A2780 sensitivity to cisplatin. Results of qRT-PCR, Western blot analysis, and luciferase reporter assay indicated that the direct target of miR-143 was DNMT3A, which, in turn, was upregulated in A2780/CDDP. DNMT3A overexpression antagonized the sensitizing effect of miR-143 on A2780/CDDP to cisplatin. Knocking down of DNMT3A reduced cisplatin resistance in A2780/CDDP, while overexpression of DNMT3A increased cisplatin resistance in A2780. Methylation-specific polymerase chain reaction results showed that the methylation level in the promoter region of the miR-143 precursor gene was higher in A2780/CDDP cells than in A2780 cells. DNMT3A mediated the hypermethylation of the miR-143 precursor gene, resulting in miR-143 downregulation in A2780/CDDP. miR-143 inhibited cell growth of A2780/CDDP cell in nude mice. Our findings indicated the negative feedback between miR-143 and DNMT3A as a crucial epigenetic modifier of cisplatin resistance in ovarian cancer.Thymoquinone (TQ), the main active constituent of Nigella sativa seeds, has been shown to play a role in antioxidation, anti-inflammation, and antitumor. Recent studies have demonstrated that TQ contributes to the suppression of liver fibrosis. Abnormal activated epithelial-mesenchymal transition (EMT) promotes the activation of hepatic stellate cells (HSCs). However, whether the antifibrotic effects of TQ occur through inhibiting EMT is largely unknown. In this study, it was found that TQ ameliorated liver fibrosis and collagen accumulation in carbon tetrachloride (CCl4) mice. In vitro, TQ inhibited HSC activation including reduced proliferation, α-smooth muscle actin, and collagen. In addition, TQ markedly suppressed the EMT process, with enhanced E-cadherin and reduced desmin. Notably, snail family transcriptional repressor 1 (Snai1), the EMT master transcription factor, was obviously inhibited by TQ in vivo and in vitro. Further studies demonstrated that Snai1 was a target of microRNA-30a (miR-30a), which was upregulated by TQ. Interestingly, the effects of TQ on HSC activation and EMT were almost inhibited by miR-30a inhibitor. Collectively, we demonstrate that TQ inhibits HSC activation, at least in part, via regulation of miR-30a and Snai1. TQ upregulates miR-30a expression, resulting in a reduced Snai1 level as well as EMT process inactivation, which contributes to the inhibition of HSC activation. TQ may be a potential therapeutic agent for liver fibrosis.The anatomy of the hair follicle and the dynamics of its barrier provide a special space for interactions between macromolecules and the underlying tissue. Translocation across the hair follicle epithelium and immune recognition have been confirmed for proteins, nucleic acids, engineered particles, virus particles and others. Tissue responses can be modulated by pro-inflammatory stimuli as demonstrated in penetration and transcutaneous immunization studies. Even under physiological conditions, hair follicle openings are filled with exogenous material ranging from macromolecules, engineered particles to natural particles including diverse communities of microbes. The exposed position of the infundibulum suggests that local inflammatory insults could disturb the finely tuned balance and may trigger downstream responses that initiate or facilitate local outbreaks of inflammatory hair diseases typically occurring in close spatial association with the infundibulum as observed in cicatricial alopecia. The question as to how microbial colonization or deposition of contaminants on the surface of the hair follicle epithelium interact with the barrier status under the influence of individual predisposition, may help us understand local flare-ups of inflammatory hair diseases. Specifically, learning more about skin barrier alterations in the different types of inflammatory hair diseases and cross-talk with exogenous compounds could give new insights in this less explored aspect of hair follicle homeostasis. Such knowledge may not only be used to develop supportive measures to maintain a healthy scalp. It may have wider implications for our understanding on how external factors influence inflammation and immunological responses in the skin.
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