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Dendritic cells (DCs) are crucial in initiating and shaping both innate and adaptive immune responses. Clinical studies and experimental models have highlighted their significant involvement in various autoimmune diseases, positioning them as promising therapeutic targets. Nicotinamide (NAM), a form of vitamin B3, with its anti-inflammatory properties, has been suggested, while the involvement of NAM in DCs regulation remains elusive. Here, through analyzing publicly available databases, we observe substantial alterations in NAM levels and NAM metabolic pathways during DCs activation. Furthermore, we discover that NAM, but not Nicotinamide Mononucleotide (NMN), significantly inhibits DCs over-activation in vitro and in vivo. The suppression of DCs hyperactivation effectively alleviates symptoms of psoriasis. Mechanistically, NAM impairs DCs activation through a Poly (ADP-ribose) polymerases (PARPs)-NF-κB dependent manner. Notably, phosphoribosyl transferase (NAMPT) and PARPs are significantly upregulated in lipopolysaccharide (LPS)-stimulated DCs and psoriasis patients; elevated NAMPT and PARPs expression in psoriasis patients correlates with higher psoriasis area and severity index (PASI) scores. In summary, our findings underscore the pivotal role of NAM in modulating DCs functions and autoimmune disorders. Targeting the NAMPT-PARP axis emerges as a promising therapeutic approach for DC-related diseases. [ABSTRACT FROM AUTHOR]

The approval of poly(ADP-ribose) polymerase (PARP) inhibitor AZD2281 in 2014 marked the successful establishment of the therapeutic strategy targeting homologous recombination repair defects of cancers in the clinic. However, AZD2281 has poor water solubility, low tissue distribution and relatively weak in vivo anticancer activity, which appears to become limiting factors for its clinical use. In this study, we found that mefuparib hydrochloride (MPH) was a potent PARP inhibitor, possessing prominent in vitro and in vivo anticancer activity. Notably, MPH displayed high water solubility (> 35 mg/ml) and potent PARP1/2 inhibition in a substrate-competitive manner. It reduced poly(ADP-ribose) (PAR) formation, enhanced γH2AX levels, induced G2/M arrest and subsequent apoptosis in homologous recombination repair (HR)-deficient cells. Proof-of-concept studies confirmed the MPH-caused synthetic lethality. MPH showed potent in vitro and in vivo proliferation and growth inhibition against HR-deficient cancer cells and synergistic sensitization of HR-proficient xenografts to the anticancer drug temozolomide. A good relationship between the anticancer activity and the PARP inhibition of MPH suggested that PAR formation and γH2AX accumulation could serve as its pharmacodynamic biomarkers. Its high bioavailability (40%~100%) and high tissue distribution in both monkeys and rats were its most important pharmacokinetic features. Its average concentrations were 33-fold higher in the tissues than in the plasma in rats. Our work supports the further clinical development of MPH as a novel PARP1/2 inhibitor for cancer therapy.

Objective: To evaluate the right ventricular functions of patients with acute organophosphate poisoning patient (AOPP) by measuring the velocities of tricuspid annular motion through Doppler tissue imaging (DTI)., Methods: Tissue Doppler velocity mode was employed to observe tricuspid annulus movement in 78 AOPP patients and 32 healthy adults. After tricuspid annular pulsed-wave rate of E/A were measured by traditional echocardiographic, the peak values of tricuspid annular early diastolic velocity (E(m)) and late diastolic velocity (A(m)) were analyzed by DTI., Results: E/A > E(m)/A(m) > 1 was observed in health control group as well as the mild-moderate AOPP; E(m)/A(m) < E/A < 1 was observed in the severe AOPP group. There was significant difference between two groups. The right ventricular E/A correlated positively with E(m)/A(m) (P < 0.001). Pulmonary arterial pressure (PAP) correlated positively with right ventricular E/Em, Tei Index (P < 0.001) and negatively with right ventricular S(m), E(m) and E(m)/A(m) (P < 0.001)., Conclusion: The right ventricle functions, in terms of contraction and relaxation, decrease in severe AOPP patients versus health control and mild-moderate groups. TDI is a useful tool to assess the right ventricle functions of AOPP patients.

Objective: To investigate the application of fluorescence in situ hybridization (FISH) technique in prenatal diagnosis of complex chromosomal abnormalities., Methods: Eleven prenatal diagnosis cases (8 from amniocentesis and 3 from cord blood) with complex chromosomal abnormalities detected by routine G-banding, were further analyzed by FISH., Results: The FISH technique confirmed the results of balanced chromosome rearrangements detected by G-banding, and clarified the structure of the derivative chromosomes in the 3 amniocentesis samples and the origin of the mark chromosomes in the 2 cord blood samples., Conclusion: FISH can be used to diagnose the complex chromosomal abnormalities accurately in prenatal diagnosis, and can provide very useful genetic information for clinical diagnosis and treatment.

Objective: To explore the use of fluorescence in situ hybridization (FISH) and high resolution-comparative genomic hybridization (HR-CGH) techniques in amenorrhea study., Methods: After routine gynecologic examination, ultrasonography and endocrine examination, 17 cases of primary amenorrhea and 1 case of secondary amenorrhea were analysed by using chromosomal diagnoses including multiplex FISH and HR-CGH analyses., Results: Among 17 cases of primary amenorrhea, 7 revealed a 46,XX karyotype; 10 cases (58.8%) had abnormal karyotype, including 3 cases of 46,XY females, 2 cases of Turner's syndrome with 45,X and 45,X/46,XX, and other 5 cases with abnormal structure of X chromosome (including partial monosomy of X,X isochromosome and X/Y mosaic). The karyotype of the patient with secondary amenorrhea was translocation between X chromosome and euchromosome., Conclusion: The using of FISH and HR-CGH can correctly diagnose the patients' karyotypes, and provide absolutely necessarily medical genetic data for clinical diagnosis and therapy.