A Novel Inhibitor of Poly(ADP-Ribose) Polymerase-1 Inhibits Proliferation of a BRCA-Deficient Breast Cancer Cell Line via the DNA Damage-Activated cGAS-STING Pathway.

Loss-of-function mutations in the Breast Cancer Susceptibility Gene (BRCA1 and BRCA2) are often detected in patients with breast cancer. Poly(ADP-ribose) polymerase-1 (PARP1) plays a key role in the repair of DNA strand breaks, and PARP inhibitors have been shown to induce highly selective killing of BRCA1/2-deficient tumor cells, a mechanism termed synthetic lethality. In our previous study, a novel PARP1 inhibitor─(E)-2-(2,3-dibromo-4,5-dimethoxybenzylidene)-N-(4-fluorophenyl) hydrazine-1-carbothioamide (4F-DDC)─was synthesized, which significantly inhibited PARP1 activity with an IC50 value of 82 ± 9 nM. The current study aimed to explore the mechanism(s) underlying the antitumor activity of 4F-DDC under in vivo and in vitro conditions. 4F-DDC was found to selectively inhibit the proliferation of BRCA mutant cells, with highly potent effects on HCC-1937 (BRCA1-/-) cells. Furthermore, 4F-DDC was found to induce apoptosis and G2/M cell cycle arrest in HCC-1937 cells. Interestingly, immunofluorescence and Western blot results showed that 4F-DDC induced DNA double strand breaks and further activated the cGAS-STING pathway in HCC-1937 cells. In vivo analysis results revealed that 4F-DDC inhibited the growth of HCC-1937-derived tumor xenografts, possibly via the induction of DNA damage and activation of the cGAS-STING pathway. In summary, the current study provides a new perspective on the antitumor mechanism of PARP inhibitors and showcases the therapeutic potential of 4F-DDC in the treatment of breast cancer.

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

Hematoporphyrin injection mediated photodynamic therapy for secondary squamous cell carcinoma of arsenical keratosis: A case report.

Hematoporphyrin injection (HpD) mediated photodynamic therapy (PDT) has demonstrated efficacy in treating various types of Bowen's disease, including basal-cell carcinoma, squamous cell carcinoma, extramammary Paget's disease, and actinic keratosis. We present a case of a male patient who developed squamous cell carcinoma as a result of repeated instances of arsenic-induced keratosis on both his hands and feet. Due to the involvement of the joint in both hands, the patient declined the conventional surgical resection treatment since it could potentially impact normal physiological function. Instead, the patient chose to undergo hemoporphyrin photodynamic therapy. After the treatment, the rash was entirely eliminated and there were no restrictions in the movement of the joint. Nevertheless, a local recurrence was detected throughout the two-year monitoring period. Arsenical keratosis carries a substantial likelihood of recurring. However, we believe that hemoporphyrin photodynamic therapy is effective in treating this condition.

Dietary additive ferulic acid alleviated oxidative stress, inflammation, and apoptosis induced by chronic exposure to avermectin in the liver of common carp (Cyprinus carpio).

Avermectin (AVM) has been utilized extensively in agricultural production since it is a low-toxicity pesticide. However, the pollution caused by its residues to fisheries aquaculture has been neglected. As an abundant polyphenolic substance in plants, ferulic acid (FA) possesses anti-inflammatory and antioxidant effects. The goal of the study is to assess the FA's ability to reduce liver damage in carp brought on by AVM exposure. Four groups of carp were created at random: the control group; the AVM group; the FA group; and the FA + AVM group. On day 30, and the liver tissues of carp were collected and examined for the detection of four items of blood lipid as well as the activity of the antioxidant enzymes catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) in carp liver tissues by biochemical kits, and the transcript levels of indicators of oxidative stress, inflammation and apoptosis by qPCR. The results showed that liver injury, inflammation, oxidative stress, and apoptosis were attenuated in the FA + AVM group compared to the AVM group. In summary, dietary addition of FA could ameliorate the hepatotoxicity caused by AVM in carp by alleviating oxidative stress, inflammation, apoptosis in liver tissues.