Pulmonary hypertension (PH) is a progressive and complex pulmonary vascular disease with poor prognosis. The aim of this study was to provide a new understanding of the lung pathology of disease and a noninvasive method in monitoring the establishment of animal models for basic and clinical studies of PH, indeed to explore clinical application value of lung ultrasound for patients with PH. Totally 32 male SD rats were randomly divided into control group, MCT (monocrotaline) group, PDTC (pyrrolidine dithiocarbamate) group, and NS (normal saline) group. Rats in the MCT group, PDTC group, and NS group received single intraperitoneal injection of MCT, while the control group received the same dose of NS. Then, PDTC group and NS group received PDTC and NS daily for treatment at the end of the model. Each group received lung ultrasound examination and measurement of pulmonary arterial pressure (PAP). Then, the rats were sacrificed to take the lung specimens to being observed. The ultrasound and pathological results were analyzed with a semiquantitative score. With the pulmonary artery pressure increases, the MCT group had a higher pulmonary ultrasound score and pathological score compared with the control group (p < 0.05). After PDTC treatment, the pulmonary ultrasound score and the pathological score decline (p < 0.05). We investigated both lung ultrasound scores, and the pathological scores were positively correlated with mean pulmonary artery pressure (mPAP) (both r > 0.8, p < 0.0001). Moreover, lung ultrasound scores were positively correlated with pathological scores (r > 0.8, p < 0.0001). We elucidated lung ultrasound evaluation providing more evidence for the management of PH in the rat model. Moreover, lung ultrasound provided a noninvasive method in monitoring the establishment of animal models for basic and clinical studies of PH.

UNASSIGNED: Cognitive impairment is a severe complication of acute respiratory distress syndrome (ARDS). Emerging studies have revealed the effects of pyrrolidine dithiocarbamate (PDTC) on improving surgery-induced cognitive impairment. The major aim of the study was to investigate whether PDTC protected against ARDS-induced cognitive dysfunction and to identify the underlying mechanisms involved.
UNASSIGNED: The rat model of ARDS was established by intratracheal instillation of lipopolysaccharide (LPS), followed by treatment with PDTC. The cognitive function of rats was analyzed by the Morris Water Maze, and pro-inflammatory cytokines were assessed by quantitative real-time PCR, enzyme-linked immunosorbent assay, and western blot assays. A dual-luciferase reporter gene assay was performed to identify the relationship between miR-181c and its target gene, TAK1 binding protein 2 (TAB2).
UNASSIGNED: The results showed that PDTC improved cognitive impairment and alleviated neuroinflammation in the hippocampus in LPS-induced ARDS model. Furthermore, we demonstrated that miR-181c expression was downregulated in the hippocampus of the ARDS rats, which was restored by PDTC treatment. In vitro studies showed that miR-181c alleviated LPS-induced pro-inflammatory response by inhibiting TAB2, a critical molecule in the nuclear factor (NF)-κB signaling pathway.
UNASSIGNED: PDTC improves cognitive impairment in LPS-induced ARDS by regulating miR-181c/NF-κB axis-mediated neuroinflammation, providing a potential opportunity for the treatment of this disease.

Anaplastic thyroid carcinoma (ATC) is the most advanced and aggressive thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) lacks anaplastic histology but has lost architectural and cytologic differentiation. Only a few studies have focused on the genetic relationship between the two advanced carcinomas and coexisting differentiated thyroid carcinomas (DTCs). In the present study, we investigated clinicopathologic features and genetic profiles in 57 ATC and PDTC samples, among which 33 cases had concomitant DTC components or DTC history. We performed immunohistochemistry for BRAF V600E, p53, and PD-L1 expression, Sanger sequencing for TERT promoter and RAS mutations, and fluorescence in situ hybridization for ALK and RET rearrangements. We found that ATCs and PDTCs shared similar gene alterations to their coexisting DTCs, and most DTCs were aggressive subtypes harboring frequent TERT promoter mutations. A significantly higher proportion of ATCs expressed p53 and PD-L1, and a lower proportion expressed PAX-8 and TTF-1, than the coexisting DTCs. Our findings provide more reliable evidence that ATCs and PDTCs are derived from DTCs.

UNASSIGNED: The clinic-pathological boundary between poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) is unclear due to a wide spectrum of histopathological features and the rarity of the disease. In addition to that, with the highest mortality rate and non-standard treatment modality, the PDTC/ATC population has not been subjected to comprehensive description and comparison with the extent of histological characteristics, therapeutic response, prognostic factors, and death attribution analysis.
UNASSIGNED: A total of 4,947 PDTC/ATC patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival curve estimation and Cox proportional hazard regression were applied.
UNASSIGNED: Overall, the 5- and 10-year DSS for PDTC were 71.9% and 68.0%, respectively, whereas the 5- and 10-year OS are 59.3% and 51.2%, respectively. The median survival time for ATC patients was 3 months with 1-year OS being 26.9% and 1-year DSS being 31.2%. During the follow-up period, 68.1% of the PDTC/ATC cohort were dead, 51.6% of which were attributed to thyroid malignancies and 16.5% to non-thyroid causes. The top three common non-thyroid causes of death were miscellaneous cancers, lower respiratory system disease, and heart disease. The histological feature of papillary thyroid cancer (PTC) was the leading pathological category for PDTC patients (51.7%), whereas 76.7% of ATC patients\' pathological feature was characterized as unidentifiable. Sarcoma histological characteristics found in ATC cases suffer the highest overall mortality (vs. PTC, HR = 2.61, 95% CI 1.68-4.06, P < 0.001). Older age unidentifiable histology feature, more advanced AJCC N1b, AJCC M1, and SEER stage, tumor size larger than 5 cm, and more invasive tumor extension were independent bad outcome predictors.
UNASSIGNED: The populational analysis of the PDTC/ATC cohort has provided reliable support for better understanding of the difference between PDTC and ATC cases and the guidance of clinical practice and further studies.

The present study was designed to explore the role of M2 macrophage‑derived exosomes (M2‑exos) on the KCa3.1 channel in a cellular atrial fibrillation (AF) model using rapidly paced HL‑1 myocytes. M2 macrophages and M2‑exos were isolated and identified. MicroRNA (miR)‑146a‑5p levels in M2 macrophages and M2‑exos were quantified using reverse transcription‑quantitative PCR (RT‑qPCR). HL‑1 myocytes were randomly divided into six groups: Control group, pacing group, pacing + coculture group (pacing HL‑1 cells cocultured with M2‑exos), pacing + mimic‑miR‑146a‑5p group, pacing + NC‑miR‑146a‑5p group and pacing + pyrrolidine dithiocarbamate (PDTC; a special blocker of the NF‑κB signaling pathway) group. Transmission electron microscopy, nanoparticle tracking analysis, western blotting, RT‑qPCR and immunohistochemistry were performed in the present study. A whole‑cell clamp was also applied to record the current density of KCa3.1 and action potential duration (APD) in each group. The results revealed that miR‑146a‑5p was highly expressed in both M2 macrophages and M2‑exos. Pacing HL‑1 cells led to a shorter APD, an increased KCa3.1 current density and higher protein levels of KCa3.1, phosphorylated (p‑)NF‑κB p65, p‑STAT3 and IL‑1β compared with the control group. M2‑exos, miR‑146a‑5p‑mimic and PDTC both reduced the protein expression of KCa3.1, p‑NF‑κB p65, p‑STAT3 and IL‑1β and the current density of KCa3.1, resulting in a longer APD in the pacing HL‑1 cells. In conclusion, M2‑exos and their cargo, which comprised miR‑146a‑5p, decreased KCa3.1 expression and IL‑1β secretion in pacing HL‑1 cells via the NF‑κB/STAT3 signaling pathway, limiting the shorter APD caused by rapid pacing.

We aimed to investigate the effects of tumor necrosis factor (TNF)-α on the expression of interferon α/β receptor subunit 1 (IFNAR1) and cervical squamous cancer (CSCC) resistance to Cisplatin, as well as the underlying mechanisms. Kaplan-Meier analysis was used to plot the overall survival curves. SiHa cells were treated with 20 ng/ml TNF-α to determine cell proliferation in human CSCC cells and the expression of IFNAR1. The effects of TNF-α on the downstream signaling pathway, including casein kinase 1α (CK1α), were investigated using the caspase protease inhibitor FK009, the c-Jun kinase inhibitor SP600125, and the nuclear factor kappa-B inhibitor ammonium pyrrolidinedithiocarbamate (PDTC). TNF-α induced down-regulation of IFNAR1 in human CSCC cells and promoted proliferation of SiHa cells. SiHa cells were transfected with the catalytic inactive mutant CK1α K49A, and the ability of TNF-α to induce down-regulation of IFNAR1 expression was found to be significantly diminished in this context. FK009 and PDTC had no obvious effect on the expression of CK1α, however, SP600125 significantly reduced the expression of CK1α in the presence of TNF-α. SiHa cells treated with TNF-α showed reduced sensitivity to Cisplatin and exhibited higher cell viability, while the sensitivity of SiHa cells to Cisplatin was restored after treatment with CK1α inhibitor D4476. Additionally, we constructed a TNF-α overexpressing SiHa cell line and a transplanted tumor model. The results were similar to those of in vitro efficacy. We demonstrate that TNF-α-induced down-regulation of type I interferon receptor contributes to acquired resistance of cervical squamous cancer to Cisplatin.

Acrolein, a common environmental pollutant, is linked to the development of cardiovascular inflammatory diseases. Pelargonidin is a natural compound with anti-inflammation activity. In this study, we aimed to explore the effects of pelargonidin on inflammation induced by acrolein in human umbilical vein endothelial cells (HUVECs). MTT assay was utilized for assessing cell viability in HUVECs. LDH release in HUVECs was measured using the LDH kit. Western blot was used to detect the protein expression of p-p65, p65 and COX-2. Inflammation was evaluated through determining the levels of PGE2, IL-1β, IL-6, IL-8 and TNF-α in HUVECs after treatment. COX-2 mRNA expression and COX-2 content were examined using RT-qPCR and a human COX-2 ELISA kit, respectively. Acrolein treatment at 50 μM resulted in a 45% decrease in the viability and an increase in LDH release (2.2-fold) in HUVECs. Pelargonidin at 5, 10, 20, and 40 μM alleviated acrolein-caused inhibitory effect on cell viability (increased to 1.3-, 1.5-, 1.8-, and 1.9-fold, respectively, compared to acrolein treatment group) and promoting effect on LDH release (decreased to 82%, 75%, 62%, and 58%, respectively, compared to acrolein treatment group) in HUVECs. Moreover, pelargonidin or pyrrolidine dithiocarbamate (PDTC; an NF-κB pathway inhibitor) inhibited acrolein-induced activation of the NF-κB pathway. Acrolein elevated the levels of PGE2, IL-1β, IL-6, IL-8 and TNF-α (from 40.2, 27.3, 67.2, 29.0, 24.8 pg/mL in control group to 224.0, 167.3, 618.3, 104.6, and 275.1 pg/mL in acrolein treatment group, respectively), which were retarded after pelargonidin (decreased to 134.8, 82.3, 246.2, 70.2, and 120.8 pg/mL in acrolein + pelargonidin treatment group) or PDTC (decreased to 107.9, 80.1, 214.6, 64.0, and 96.6 pg/mL in acrolein + PDTC treatment group) treatment in HUVECs. Pelargonidin inactivated the NF-κB pathway to reduce acrolein-induced COX-2 expression. Furthermore, pelargonidin relieved acrolein-triggered inflammation through decreasing COX-2 expression by inactivating the NF-κB pathway in HUVECs. In conclusion, pelargonidin could protect against acrolein-triggered inflammation in HUVECs through attenuating COX-2 expression by inactivating the NF-κB pathway.

Many studies have recently highlighted the role of photobiomodulation (PBM) in neuropathic pain (NP) relief after spinal cord injury (SCI), suggesting that it may be an effective way to relieve NP after SCI. However, the underlying mechanisms remain unclear. This study aimed to determine the potential mechanisms of PBM in NP relief after SCI.
We performed systematic observations and investigated the mechanism of PBM intervention in NP in rats after SCI. Using transcriptome sequencing, we screened CXCL10 as a possible target molecule for PBM intervention and validated the results in rat tissues using reverse transcription-polymerase chain reaction and western blotting. Using immunofluorescence co-labeling, astrocytes and microglia were identified as the cells responsible for CXCL10 expression. The involvement of the NF-κB pathway in CXCL10 expression was verified using inhibitor pyrrolidine dithiocarbamate (PDTC) and agonist phorbol-12-myristate-13-acetate (PMA), which were further validated by an in vivo injection experiment.
Here, we demonstrated that PBM therapy led to an improvement in NP relative behaviors post-SCI, inhibited the activation of microglia and astrocytes, and decreased the expression level of CXCL10 in glial cells, which was accompanied by mediation of the NF-κB signaling pathway. Photobiomodulation inhibit the activation of the NF-κB pathway and reduce downstream CXCL10 expression. The NF-κB pathway inhibitor PDTC had the same effect as PBM on improving pain in animals with SCI, and the NF-κB pathway promoter PMA could reverse the beneficial effect of PBM.
Our results provide new insights into the mechanisms by which PBM alleviates NP after SCI. We demonstrated that PBM significantly inhibited the activation of microglia and astrocytes and decreased the expression level of CXCL10. These effects appear to be related to the NF-κB signaling pathway. Taken together, our study provides evidence that PBM could be a potentially effective therapy for NP after SCI, CXCL10 and NF-kB signaling pathways might be critical factors in pain relief mediated by PBM after SCI.

Gold ions have high activity and cytotoxicity completely different from elemental gold. It is necessary and critical to develop Au3+ detection tools that are easy to operate, intuitive, inexpensive, and non-destructive testing. Here, we propose a novel two-photon fluorescent probe named DA for detecting Au3+, which is a rare combination of dicoumarin with dimethylthiocarbamate for the first time. Based on the PET mechanism, DA turns-on the fluorescence to yellow-green after specifically binds to Au3+, and the reaction is completed within 5 min. The detection limit is as low as 27.60 nM. Simultaneously, DA achieved qualitative and quantitative detection of Au3+ in environmental water samples, and fluorescence imaging of Au3+ in biological cells.

Thiocarbamates could be synthesized in green solvents via thiol-dioxazolone modified Lossen rearrangement under transition-metal free, additive free, and mild conditions. Polythiocarbamates were further prepared with excellent self-healing and shape-memory properties, showing great potential in the development of functional materials.