Tumor-derived extracellular vesicles in melanoma immune response and immunotherapy.

Tumor-derived extracellular vesicles (EVs) are key immune regulators of the tumor microenvironment. They reshape the immune microenvironment and prevent antitumor immune responses via their immunosuppressive cargo, thereby determining cancer responsiveness to treatment. In the immune microenvironment of melanoma, tumor-derived EVs influence tumor progression by regulating innate and adaptive immune responses. Tumor-derived EV-based therapy is a cutting-edge and promising strategy for inhibiting melanoma progression and enhancing antitumor immunity. This review aimed to summarize the regulatory roles of EVs in the immune responses and immunotherapy of patients with melanoma. This paper provided insights into future exploration directions and potential clinical strategies targeting EVs for melanoma treatment.

A near-infrared phosphorescent iridium(iii) complex for fast and time-resolved detection of cysteine and homocysteine.

Thiol-containing amino acids, cysteine (Cys) and homocysteine (Hcy), play crucial roles in the biosystem; their abnormal contents in the cells are linked to many diseases. Herein, we designed and synthesized a novel near-infrared (NIR) phosphorescent iridium(iii) complex-based probe (FNO1) that can detect Cys and Hcy in real-time in the biosystem. Due to the advantages of the iridium complex, the FNO1 probe had excellent chemical stability and photostability, high luminescence efficiency, and long luminescence lifetime. In addition, the probe showed a fast response, high sensitivity, and low cytotoxicity. As verified by high resolution mass spectra (HR-MS) and density functional theory (DFT) calculations, the detection was achieved through the addition of the α,ß-unsaturated ketone group in FNO1 by the nucleophilic thiol group in Cys and Hcy. Through time-resolved emission spectroscopy (TRES) and in the presence of a strongly fluorescent dye rhodamine B, the FNO1 probe could detect Cys and Hcy due to its long luminescence lifetime (260/197 ns). Finally, owing to its NIR-emitting properties, the FNO1 probe was successfully applied in the imaging of Cys and Hcy in living cells, zebrafish, and mice.

A time-resolved near-infrared phosphorescent iridium(iii) complex for fast and highly specific peroxynitrite detection and bioimaging applications.

Peroxynitrite (ONOO-), one of the reactive oxygen/nitrogen species (ROS/RNS) found in vivo, plays crucial roles in many physiological and pathological processes. The ability to selectively and sensitively determine ONOO-in vivo is important for the understanding of its biological roles. Thus, by utilizing the excellent chemical stability and photostability, high luminescence efficiency, and long luminescence lifetime of iridium complexes, we developed a novel near-infrared (NIR) phosphorescent iridium(iii) complex (FNO2) probe to detect ONOO- within seconds. The probe FNO2 showed better selectivity towards ONOO- over other interfering biomolecules, including O2- and ClO-. Moreover, it possessed a long luminescence lifetime, which enabled successful elimination of the interference from background fluorescence in vitro (simulated by Rhodamine B) in time-resolved emission spectra. Finally, in addition to its low cytotoxicity, the probe FNO2 showed emission wavelength in the NIR region and was able to specifically sense ONOO- induced in living cells and inflamed mouse models.

A near-infrared xanthene fluorescence probe for monitoring peroxynitrite in living cells and mouse inflammation model.

Peroxynitrite (ONOO-) plays important roles in the regulation of many physiological and pathological processes, and an increase in its levels is related to numerous diseases. Thus, accurate detection of ONOO- in physiological conditions is imperative for elucidating its functions. However, studies on high signal-to-noise-ratio (SNR) fluorescence imaging of ONOO-in vivo for its detection are currently lacking. Thus, a novel NIR xanthene fluorescence probe (NOF2) for the endogenous detection of ONOO- is designed and synthesized. The fluorescence of the NOF2 probe is pre-quenched by the hydroxyl protection group of diphenyl phosphinate. Additionally, the NOF2 probe exhibits good selectivity and sensitivity for ONOO- with a low detection limit of 0.40 µM. Importantly, the NOF2 probe displays good performances for the detection of endogenous ONOO- not only in living cells but also in a mouse inflammation model. This demonstrates its great potential for applications involving the detection of ONOO- both in vitro and in vivo to explore the roles of ONOO- in different physiological systems.

The first-trimester maternal serum cyclophilin A concentrations in women with complicated pregnancy as preeeclampsia.

BACKGROUND: Cyclophilin A (CyPA) is a potential mediator of inflammation. We assessed the predictive value of the first-trimester maternal serum CyPA concentrations for complicated pregnancy. METHODS: The first-trimester serum CyPA concentrations were quantified in 100 women with normal pregnancy and in 351 women with complicated pregnancy, including 102 pre-eclampsia women, 131 gestational hypertension (GH) women and 118 gestational diabetes mellitus (GDM) women. Its association with complicated pregnancy was ascertained using multivariate analysis. RESULTS: Median CyPA concentrations were significantly higher in women developing complicated pregnancy as pre-eclampsia, GH or GDM than in women with normal pregnancy. CyPA concentrations were independently correlated with C-reactive protein concentrations in complicated pregnancy as pre-eclampsia, GH or GDM women. Serum CyPA and body mass index were independently associated with the development of complicated pregnancy as pre-eclampsia, GH or GDM. Serum CyPA possessed significantly high area under receiver operating characteristic curve. Meanwhile, CyPA significantly improved the predictive value of body mass index. CONCLUSIONS: Serum CyPA might be utilized as a potential inflammatory biomarker for complicated pregnancy and assessment of serum CyPA might aid in the prediction of complicated pregnancy.

Antinociceptive Effects of Prim-O-Glucosylcimifugin in Inflammatory Nociception via Reducing Spinal COX-2.

We measured anti-nociceptive activity of prim-o-glucosylcimifugin (POG), a molecule from Saposhnikovia divaricate (Turcz) Schischk. Anti-nociceptive or anti-inflammatory effects of POG on a formalin-induced tonic nociceptive response and a complete Freund's adjuvant (CFA) inoculation-induced rat arthritis pain model were studied. Single subcutaneous injections of POG produced potent anti-nociception in both models that was comparable to indomethacin analgesia. Anti-nociceptive activity of POG was dose-dependent, maximally reducing pain 56.6% with an ED50 of 1.6 mg. Rats given POG over time did not develop tolerance. POG also time-dependently reduced serum TNFα, IL-1ß and IL-6 in arthritic rats and both POG and indomethacin reduced spinal prostaglandin E2 (PGE2). Like indomethacin which inhibits cyclooxygenase-2 (COX-2) activity, POG dose-dependently decreased spinal COX-2 content in arthritic rats. Additionally, POG, and its metabolite cimifugin, downregulated COX-2 expression in vitro. Thus, POG produced potent anti-nociception by downregulating spinal COX-2 expression.

Subhaplogroup D4b1 enhances the risk of cervical cancer initiation: A case-control study in southern China.

AIM: To investigate whether mitochondrial DNA (mtDNA) background (haplogroup) is associated with cervical cancer in patients in southern China. METHODS: A case-control study of 150 patients with cervical cancer and 217 geographically matched controls was conducted in Wenzhou, a southern Chinese city in the Zhejiang province. DNA from peripheral blood was extracted and sequenced. Sequences were aligned to the mtDNA revised Cambridge Reference Sequence (GenBank number NC_012920) to determine mtDNA single nucleotide polymorphisms (SNPs) and haplogroups. RESULTS: We found that both M and N haplogroups and their diagnostic SNPs (A10398G and C10400T) are not associated with the risk of cervical cancer. However, individuals with haplogroup D4b1/D4b1*, an M subhaplogroup, exhibited an increased risk of cervical cancer (odds ratio [OR] = 1.034; 95% confidence interval [CI] 1.004, 1.066; P = 0.011/OR =1.027; 95% CI 1.001, 1.055; P = 0.027). Individuals with SNPs C10181T/A10136G (OR =1.034; 95% CI 1.004, 1.066; P = 0.011/OR =1.027; 95% CI 1.001, 1.055; P = 0.027) were more susceptible to cervical cancer than individuals without. Furthermore, we determined that mtDNA background is not associated with the progression of cervical cancer. CONCLUSIONS: Our results indicate that mtDNA haplogroups play a role in cervical cancer initiation.