Gallic acid pretreatment mitigates parathyroid ischemia-reperfusion injury through signaling pathway modulation.

Thyroid surgery often results in ischemia-reperfusion injury (IRI) to the parathyroid glands, yet the mechanisms underlying this and how to ameliorate IRI remain incompletely explored. Our study identifies a polyphenolic herbal extract-gallic acid (GA)-with antioxidative properties against IRI. Through flow cytometry and CCK8 assays, we investigate the protective effects of GA pretreatment on a parathyroid IRI model and decode its potential mechanisms via RNA-seq and bioinformatics analysis. Results reveal increased apoptosis, pronounced G1 phase arrest, and significantly reduced cell proliferation in the hypoxia/reoxygenation group compared to the hypoxia group, which GA pretreatment mitigates. RNA-seq and bioinformatics analysis indicate GA's modulation of various signaling pathways, including IL-17, AMPK, MAPK, transient receptor potential channels, cAMP, and Rap1. In summary, GA pretreatment demonstrates potential in protecting parathyroid cells from IRI by influencing various genes and signaling pathways. These findings offer a promising therapeutic strategy for hypoparathyroidism treatment.

Exploring the diagnostic value of endothelial cell and angiogenesis-related genes in Hashimoto's thyroiditis based on transcriptomics and single cell RNA sequencing.

(1) BACKGROUND: Hashimoto's thyroiditis (HT) can cause angiogenesis in the thyroid gland. However, the molecular mechanism of endothelial cells and angiogenesis related genes (ARGs) has not been extensively studied in HT. (2) METHODS: The HRA001684, GSE29315 and GSE163203 datasets were included in this study. Using single-cell analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, machine learning algorithms and expression analysis for exploration. And receiver operator characteristic (ROC) curves was draw. Gene set enrichment analysis (GSEA) was utilized to investigate the biological function of the biomarkers. Meanwhile, we investigated into the relationship between biomarkers and different types of immune cells. Additionally, the expression of biomarkers in the TCGA-TC dataset was examined and the mRNA-drug interaction network was constructed. (3) RESULTS: We found 14 cell subtypes were obtained in HT samples after single-cell analysis. A total of 5 biomarkers (CD52, CD74, CD79A, HLA-B and RGS1) were derived, and they had excellent diagnostic performance. Then, 27 drugs targeting biomarkers were predicted. The expression analysis showed that CD74 and HLA-B were significantly up-regulated in HT samples. (4) CONCLUSION: In this study, 5 biomarkers (CD52, CD74, CD79A, HLA-B and RGS1) were screened and their expressions in endothelial cells was compared to offer a new reference for the recognition and management of HT.

A deep learning model for the differential diagnosis of benign and malignant salivary gland tumors based on ultrasound imaging and clinical data.

Background: The preoperative differentiation between benign parotid gland tumors (BPGTs) and malignant parotid gland tumors (MPGTs) is of great significance for therapeutic decision-making. Deep learning (DL), an artificial intelligence algorithm based on neural networks, can help overcome inconsistencies in conventional ultrasonic (CUS) examination outcomes. Therefore, as an auxiliary diagnostic tool, DL can support accurate diagnosis using massive ultrasonic (US) images. This current study developed and validated a DL-based US diagnosis for the preoperative differentiation of BPGT from MPGT. Methods: A total of 266 patients, including 178 patients with BPGT and 88 patients with MPGT, were consecutively identified from a pathology database and enrolled in this study. Ultimately, considering the limitations of the DL model, 173 patients were selected from the 266 patients and divided into 2 groups: a training set, and a testing set. US images of the 173 patients were used to construct the training set (including 66 benign and 66 malignant PGTs) and testing set (consisting of 21 benign and 20 malignant PGTs). These were then preprocessed by normalizing the grayscale of each image and reducing noise. Processed images were imported into the DL model, which was then trained to predict the images from the testing set and evaluated for performance. Based on the training and validation datasets, the diagnostic performance of the 3 models was assessed and verified using receiver operating characteristic (ROC) curves. Ultimately, before and after combining the clinical data, we compared the area under the curve (AUC) and diagnostic accuracy of the DL model with the opinions of trained radiologists to evaluate the application value of the DL model in US diagnosis. Results: The DL model showed a significantly higher AUC value compared to doctor 1 + clinical data, doctor 2 + clinical data, and doctor 3 + clinical data (AUC =0.9583 vs. 0.6250, 0.7250, and 0.8025 respectively; all P<0.05). In addition, the sensitivity of the DL model was higher than the sensitivities of the doctors combined with clinical data (97.2% vs. 65%, 80%, and 90% for doctor 1 + clinical data, doctor 2 + clinical data, and doctor 3 + clinical data, respectively; all P<0.05). Conclusions: The DL-based US imaging diagnostic model has excellent performance in differentiating BPGT from MPGT, supporting its value as a diagnostic tool for the clinical decision-making process.

Salvage high intensity focused ultrasound for residual or recurrent cervical cancer after definitive chemoradiotherapy.

Objective: The treatment of residual/recurrent cervical cancer within a previously irradiated area is challenging and generally associated with a poor outcome. Local treatments such as salvage surgery and re-irradiation are usually traumatic and have limited efficacy. High intensity focused ultrasound (HIFU) treatment can directly ablate solid tumors without damaging neighboring healthy tissue. However, the HIFU studies for these patients are limited. Experience gained over the course of 10 years with the use of HIFU for the management of residual/recurrent cervical cancer after chemoradiotherapy is reported herein. Methods: 153 patients with residual/recurrent cervical cancer in a previously irradiated field who received HIFU treatment between 2010 and 2021 were retrospectively analyzed. Adverse effects, survival benefit and factors affecting prognosis were given particular attention. Results: A total of 36 patients (23.5%) achieved a partial response following HIFU treatment and 107 patients (69.9%) had stable disease. The objective response and disease control rates were 23.5% and 93.5%, respectively. The median progression-free survival (mPFS) and median overall survival (mOS) were 17.0 months and 24.5 months, respectively. Moreover, patients with lesions ≥1.40 cm before HIFU treatment and a shrinkage rate ≥ 30% after treatment had a higher mPFS and mOS, and patients with lesions ≤1.00 cm after HIFU treatment had a higher mPFS (P=<0.05). All the treatment-related adverse events were limited to minor complications, which included skin burns, abdominal pain and vaginal discharge. Conclusions: HIFU treatment is likely a preferred option for cervical cancer patients with residual disease or recurrence following CRT that can safely improve the local control rate and extend survival.

Polysaccharide from Echinacea purpurea plant ameliorates oxidative stress-induced liver injury by promoting Parkin-dependent autophagy.

BACKGROUND: Acetaminophen (APAP) overdose represents one of the most common drug-induced liver injuries (DILI) worldwide. Oxidative damage to the hepatocytes and their resultant autophagy are the key components in the APAP-induced DILI. Echinacea purpurea polysaccharide (EPPS), the component extracted from the root of Echinacea purpurea (L.) Moench, shows various biological functions including immunoregulation and antioxidant activity. PURPOSE: This study aimed to elucidate the protective effect of EPPS against APAP-induced DILI and the underlying mechanisms. RESULTS: EPPS attenuates APAP overdose induced DILI in mice and ameliorates inflammation and oxidative stress in mice with APAP overdose-induced DILI. Furthermore, EPPS protected the hepatocytes against APAP-induced liver injury by suppressing apoptosis. EPPS ameliorates APAP-induced DILI via an autophagy-dependent mechanism in vivo and increases autophagy with a reduction in oxidative stress and inflammation in vitro. Parkin knockdown prevents the autophagic-dependent manner of EPPS effects in APAP-treated hepatocytes. CONCLUSIONS: EPPS exhibited a strong hepatoprotective effect against APAP-induced DILI and was correlated with reduction of autophagy-dependent oxidant response, inflammation, and apoptosis. Moreover, the findings indicated that EPPS exerts its hepatoprotective effect against APAP mainly via Parkin-dependent autophagy, and the use of EPPS can serve as a promising novel therapeutic strategy for APAP-induced DILI.

Increased sensitivity of BCR-ABL-induced B-ALL to imatinib by releasing leukemia B cell differentiation blockage.

AIMS: In B cell acute lymphocytic leukemia (B-ALL), B cells are blocked mainly at the pro/pre-B phase, making them poorly responsive to imatinib. We aimed to investigate whether it was possible to promote pro/pre-B cell maturation beyond this phase and make them sensitive to imatinib treatment by overexpressing immunoregulatory tyrosine activation motif (ITAM) with BCR-ABL in a Ph+ B-ALL mouse model. MATERIALS & METHODS: Ph+ B-ALL mouse models were induced by BCR-ABL using retroviral transduction/transplantation. RESULTS: Overexpression of ITAM promoted the differentiation of blocked pro/pre-B cells to B220+IgM+ and increased disease sensitivity to imatinib in mice. Btk deficiency accelerated the progression of BCR-ABL-induced B-ALL. CONCLUSION: B-cell development blockage released by ITAM renders leukemia cells sensitive to imatinib treatment in BCR-ABL-induced B-ALL.

Draft genomic sequence of Armillaria gallica 012m: insights into its symbiotic relationship with Gastrodia elata.

Armillaria species (Basidiomycota, Physalacriaceae) are well known as plant pathogens related to serious root rot disease on various trees in forests and plantations. Interestingly, some Armillaria species are essential symbionts of the rare Chinese medicinal herb Gastrodia elata, a rootless and leafless orchid used for over 2000 years. In this work, an 87.3-M draft genome of Armillaria gallica 012m strain, which was symbiotic with G. elata, was assembled. The genome includes approximately 23.6% repetitive sequences and encodes 26,261 predicted genes. In comparison with other four genomes of Armillaria, the following gene families related to pathogenicity/saprophytic phase, including cytochrome P450 monooxygenases, carbohydrate-active enzyme AA3, and hydrophobins, were significantly contracted in A. gallica 012m. These characteristics may be beneficial for G. elata to get less injuries. The genome-guided analysis of differential expression between rhizomorph (RH) and vegetative mycelium (VM) showed that a total of 2549 genes were differentially expressed, including 632 downregulated genes and 1917 upregulated genes. In the RH, most differentially expressed genes (DEGs) related to pathogenicity were significantly upregulated. To further elucidate gene function, Gene Ontology enrichment analysis showed that the upregulated DEGs significantly grouped into monooxygenase activity, hydrolase activity, glucosidase activity, extracellular region, fungal cell wall, response to xenobiotic stimulus, response to toxic substance, etc. These phenomena indicate that RH had better infection ability than VM. The infection ability of RH may be beneficial for G. elata to obtain nutrition, because the rhizomorph constantly infected the nutritional stems of G. elata and formed the hyphae that can be digested by G. elata. These results clarified the characteristics of A. gallica 012m and the reason why the strain 012m can establish a symbiotic relationship with G. elata in some extent from the perspective of genomics.

Dosimetric Comparison Between Jaw Tracking and No Jaw Tracking in Intensity-Modulated Radiation Therapy.

PURPOSE: This article compares the dosimetric differences between jaw tracking and no jaw tracking technique in static intensity-modulated radiation therapy plans of large and small tumors. METHODS: Eight plans with large tumor (nasopharyngeal carcinoma, volume range: 510.9 to 768.0 cm3) and 8 plans with small tumor (single brain metastasis, volume range: 5.3 to 9.9 cm3) treated with jaw tracking on Varian EDGE LINAC were chosen and recalculated with no jaw tracking to study the dosimetric differences. We compared the differences of organ-at-risk doses (Dmax, Dmean), monitor units, and γ passing rate of plan verification (3mm/3%, threshold 10%; 2mm/2%, threshold 10%) between the 2 techniques. RESULTS: The organ-at-risk doses of nasopharyngeal carcinoma cases having jaw tracking are all less than those with no jaw tracking. The Dmax and Dmean of organ-at-risks reduced 0.61% to 17.65% and 2.17% to 19.32%, P < .05, respectively. In cases with single brain metastasis, the organ-at-risk doses with jaw tracking were also lower than no jaw tracking. The Dmax and Dmean of organ-at-risk doses reduced 0.84% to 1.52% and 0.90% to 1.86%, P < .05, respectively. The monitor units for the large tumor and small tumor were increased by 2.41% and 1.1%, respectively. The γ passing rates (3mm/3%, th10%; 2mm/2%, th10%) of nasopharyngeal carcinoma plans are 99.89% ± 0.06% (jaw tracking) versus 99.56% ± 0.19% (no jaw tracking; P = .127); 97.15% ± 0.98% (jaw tracking) versus 91.90% ± 1.40% (no jaw tracking; P = .000), and the γ passing rates (3mm/3%, th10%; 2mm/2%, th10%) of brain metastasis plans are 99.97% ± 0.05% (jaw tracking) versus 99.44% ± 1.24% (no jaw tracking; P = .251), 98.65% ± 1.27% (jaw tracking) versus 93.35% ± 2.72% (no jaw tracking; P = .000). CONCLUSION: Jaw tracking can reduce the dose of organ-at-risks compared to no jaw tracking, and the effect is more significant for plans with large tumor. The γ passing rate of plans with jaw tracking is also higher than the plans with no jaw tracking. Although the monitor units in plans of jaw tracking will increase slightly, it is recommended to use jaw tracking in static intensity-modulated radiation therapy both in large and in small tumors.

Effect of honghua (Flos Carthami) on nitric oxide production in RAW 264.7 cells and alpha-glucosidase activity.

OBJECTIVE: To study the effects of extracts from Honghua (Flos Carthami) on lipopolysaccharide induced nitric oxide (NO) production in RAW 264.7 cells and the influence of the extracts on yeast a-glucosidase activity. The total flavonoid content of the extracts was also determined. METHODS: Cytotoxicity of the extracts to RAW 264.7 cells was evaluated by the ATPlite method. Inhibitory effects of the extracts on NO production were evaluated by Griess assay. Curcumin was used as a positive control. Screening of extracts for potential a-glucosidase inhibitors was done by a fluorometric assay. The assay was based on the hydrolysis of 4-methylumbelliferyl-a-D-glucopyranoside to form the fluorescent product, 4-methylumbelliferone. Acarbose was used as a positive control. The total flavonoid content was tested using kaempferol as the standard. RESULTS: There were significant inhibitory effects on NO production when the extracts were 25-100 microg/ mL (P < 0.05) and curcumin was 2-4 microg/mL (P < 0.001). The extracts showed an inhibitory effect on alpha-glucosidase activity at the concentrations of 15.6-125 microg/mL with a half maximal (50%) inhibitory concentration (IC50) of (32.8 +/- 5.7) microg/mL, compared with the IC50 of acarbose at (1.8 +/- 0.4) microg/mL. There was a significant difference between the two IC50 values (P < 0.001). The total content of flavonoids per gram of dried herb was 1.14 mg. CONCLUSION: Honghua (Flos Carthami) showed inhibitory effects on NO production in activated RAW 264.7 macrophage cells and an inhibitory effect on yeast alpha-glucosidase. There might be a relationship between these pharmacological effects and its flavonoid content.