ABSTRACT
Cyclic neutropenia (CyN) is a rare, ELANE-related neutropenia. Oral manifestations are among the initial signs of CyN and an important reason that leads patients to seek professional help. This case report describes a 12-year-old girl with recurrent oral ulcers, severe chronic periodontitis, and pathological tooth migration as the initial and main clinical symptoms of CyN. Two novel mutations in ELANE, c.180T>G (p.I60M) and c.182C>G (p.A61G) associated with CyN were observed. Bioinformatics research indicated lower stability and impaired molecular linkages of the mutant neutrophil elastase (NE) encoded by ELANE. However, the enzyme affinity to the classic substrate Suc-Ala-Ala-Ala-pNA was not substantially changed, suggesting that the impaired integrity and stability of the mutant NE, rather than catalytic deficiency, might be the pathogenic mechanism of ELANE mutation-induced neutropenia. The patient was prescribed scaling and root planing (SRP) and monthly periodontal maintenance without systemic management. Although the routine periodontal treatment was occasionally interrupted by the 2019 coronavirus pandemic, her periodontal devastation remained well-remitted in the 5-year follow-up assessment. The results of this study confirmed the importance of plaque control and proper diagnosis in the periodontal management of such patients and provide better clinical references. In addition, the novel mutations identified in this study expand the spectrum of known ELANE mutations in CyN and further contribute to knowledge regarding its pathogenic mechanism.
ABSTRACT
Salvianolic acid B (SAB) is an active phytocomponent of a popular Chinese herb called Radix Salvia militiorrhiza with numerous biological properties. The anti-psoriasis activity of SAB was examined by evaluating various psoriasis inflammatory and keratin markers against imiquimod (IMQ)-induced psoriasis on BALB/c mice. Totally 50 healthy BALB/c mice were evenly divided into 5 groups including control, drug control (SAB; 40 mg/kg), IMQ-induced psoriasis (5%), IMQ exposure and treated with SAB (40 mg/kg), or standard methotrexate (MTX; 1 mg/kg). Mice supplemented with either SAB or MTX significantly lowered the values of psoriasis area severity index (PASI), erythema, scaling, skin thickness, inflammatory markers (interleukin [IL]-22/23/17A/1ß/6) and lipid peroxidation product (malondialdehyde). Also, IMQ exposed BALB/c mice treated with SAB or MTX display lesser histopathological changes with enhanced antioxidant activities (catalase, superoxide dismutase). Moreover, the protein expression of keratin markers (K16 and K17) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling proteins (pAkt/Akt and pPI3K/PI3K) were significantly downregulated after administration with SAB and MTX as compared with IMQ induced mice. Taking together, SAB and MTX significantly ameliorate psoriatic changes by inhibiting psoriatic inflammatory and keratin markers through abolishing PI3K/Akt signaling pathway. However, further studies (clinical trials) are needed to confirm the anti-psoriatic property of SAB before recommending to psoriasis patients.
ABSTRACT
The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health and there is currently no effective antiviral therapy. It has been suggested that Chloroquine (CQ) and hydroxychloroquine (HCQ), which were primarily employed as prophylaxis and treatment for malaria, could be used to treat COVID-19. CQ and HCQ may be potential inhibitors of SARS-CoV-2 entry into host cells, which is mediated via the angiotensin-converting enzyme 2 (ACE2), and may also inhibit subsequent intracellular processes which lead to COVID-19, including damage to the cardiovascular system. However, paradoxically, CQ and HCQ have also been reported to cause damage to the cardiovascular system. In this review, we provide a critical examination of the published evidence. CQ and HCQ could potentially be useful drugs in the treatment of COVID-19 and other ACE2 involved virus infections, but the antiviral effects of CQ and HCQ need to be tested in more well-designed clinical randomized studies and their actions on the cardiovascular system need to be further elucidated. However, even if it were to turn out that CQ and HCQ are not useful drugs in practice, further studies of their mechanism of action could be helpful in improving our understanding of COVID-19 pathology.