Pemphigus foliaceus (PF) is a superficial form of pemphigus. Treatment options for PF resemble pemphigus vulgaris, including glucocorticosteroids, immunosuppressive agents and rituximab et al. These ...treatment approaches can effectively improve the condition but may also be accompanied by high risks of side effects. Therefore, it is crucial to find a safe and effective treatment options for patients with PF. It will not only benefit/be necessary for patients who refuse glucocorticosteroids or immunosuppressive agents treatments, but also for patients who cannot be treated with glucocorticosteroids or immunosuppressive agents. Herein, we reported a case of PF that was treated with apremilast without systemic glucocorticosteroids or immunosuppressive agents. A 54-year-old woman presented with itchy erythema and erosions on the trunk for more than 1 month. The patient applied mometasonefuroate cream without improvement for a duration of two weeks. The past history of diabetes mellitus and atrophic gastritis was reported. Physical examination revealed scattered erythematous macules and erosions on the trunk. No mucosal involvement was observed. The condition was assessed by the pemphigus disease area index and numerical rating scale, with baseline scores of 7 and 8, respectively. Histopathological examination showed acantholysis and intraepithelial blister. Direct immunofluorescence revealed the presence of IgG and Complement 3 deposition between the acanthocytes with the reticular distribution. Based on enzyme-linked immunosorbent assay results, the levels of Dsg1 and Dsg3 antibodies were 28.18 and 0.26 kU/L respectively. The diagnosis of PF was made. This patient was successfully treated with apremilast without systemic glucocorticosteroids or immunosuppressive agents. The patient has continued with apremilast 30mg once daily for maintenance and no adverse events related to apremilast such as gastrointestinal side effects were observed during the 9-month follow-up period. In conclusion, apremilast therapy without systemic glucocorticosteroids nor immunosuppressive agents might provide an effective alternative to management of mild PF without obvious side effect.
•CsA is the most effective and strongest evidence-based immunosuppressant for CSU.•Chinese herbal extract-TG, can be an effective treatment for CSU.•MTX did not provide any additional benefit ...compared to H1 antihistamines alone.
Immunosuppression is an integral part of treating chronic spontaneous urticaria (CSU), but there is no literature to evaluate the efficacy of multiple immunosuppressive agents.
The comparison of the efficacy, safety, and incidence of adverse effects of four immunosuppressive medicines (tripterygium glycosides, methotrexate, cyclosporine A, and azathioprine) in combination with antihistamines in treating CSU provides a clinical reference and evidence-based medicine for treating CSU.
PUBMED, The Cochrane Library, EMBASE, WANFANG, CNKI, CBM, and clinical trial registration platform were searched to collect relevant randomized controlled trials (RCT) and cohort studies of four immunosuppressive medicines combined with antihistamines for treating CSU. The primary outcomes were the efficacy of weekly urticaria activity score 7 (UAS7) and adverse effects.
This study pooled data from seven randomized clinical trials with 410 participants. The standardized mean differences for change in UAS7 were 0.10 (95% confidence interval (CI), 0.01 to 0.68) for cyclosporine A plus antihistamine; 0.03 (95% CI, 0.00 to 0.23) for azathioprine plus antihistamine; 0.52 (95% CI, 0.32 to 0.85) for tripterygium glycosides plus antihistamine; and 1.54 (95% CI, 0.64 to 3.67) for methotrexate plus antihistamine. There were no significant differences in side effects between these medicines in the limited number of trials and clinical samples.
Our results indicate that cyclosporine A combined with antihistamine resulted in greater improvements regarding the UAS7 in CSU patients and that tripterygium glycosides are also effective in treating CSU.
Comprehensive cancer treatments have been widely studied. Traditional treatment methods (e.g., radiotherapy, chemotherapy), despite ablating tumors, inevitably damage normal cells and cause serious ...complications. Photodynamic therapy (PDT), with its low rate of trauma, accurate targeting, synergism, repeatability, has displayed great advantages in the treatment of tumors. In recent years, nanotech-based PDT has provided a new modality for cancer treatment. Direct modification of PSs by nanotechnology or the delivery of PSs by nanocarriers can improve their targeting, specificity, and PDT efficacy for tumors. In this review, we strive to provide the reader with a comprehensive overview, on various aspects of the types, characteristics, and research progress of photosensitizers and nanomaterials used in PDT. And the application progress and relative limitations of nanotech-PDT in non-melanoma skin cancer and melanoma are also summarized.
Abstract Interleukin-17A therapeutic inhibitors are among the most effective treatment methods for moderate-to-severe plaque psoriasis (PP). Reflectance confocal microscopy is a non-invasive imaging ...technique already documented to be beneficial in evaluating the follow-up of PP under treatment with topical actives and phototherapy. This study aimed to assess the epidermal and dermal changes associated with psoriasis and its treatment with RCM during systemic secukinumab treatment in patients with moderate-to-severe PP. A pilot study was conducted to evaluate RCM as a non-invasive tool for monitoring secukinumab treatment in patients with PP. For patients receiving secukinumab treatment, lesional skin was selected for RCM imaging, which were recorded at all scheduled times. The RCM evaluation criteria were established based on the histopathological diagnostic criteria for psoriasis. The clinical severity of psoriasis was assessed utilizing the psoriasis area severity index. A total of 23 patients with PP were included in the study. Each patient received 300 mg of subcutaneous secukinumab as induction therapy at baseline and weeks 1–4, followed by maintenance therapy every four weeks. Microscopic confocal changes were observed during the treatment. The results identified early microscopic evidence of the anti-inflammatory activity of secukinumab, which was not detected during the clinical examination. RCM findings correlating with the PASI were used to observe the patient’s response to treatment and were identified as follows: acanthosis and parakeratosis, presence of epidermal and dermal inflammatory cells, presence of non-edge dermal papillae, and vascularization in the papillary dermis. This study is the first to demonstrate the use of RCM as an effective tool for non-invasive monitoring of secukinumab therapeutic response at a cellular level in a clinical or research setting. Early detection of RCM parameters associated with secukinumab activity may facilitate the identification of an early treatment response. RCM appears to be capable of providing practical and helpful information regarding follow-up in patients with PP undergoing secukinumab treatment. RCM may also provide novel perspectives on the subclinical evaluation of PP’s response to biological therapy.
Argonaute proteins (Agos) from thermophilic archaea are involved in several important processes, such as host defense and DNA replication. The catalytic mechanism of Ago from different microbes with ...great diversity and genome editing potential is attracting increasing attention. Here, we describe an Argonaute from hyperthermophilic
Ferroglobus placidus
(
Fp
Ago), with a typical DNA-guided DNA endonuclease activity but adopted with only a short guide 15–20 nt length rather than a broad guide selectivity for reported Agos.
Fp
Ago performed the precise cleavage of phosphodiester bonds between 10 and 11 nt on the target strand (counting from the guide strand) guided strictly by 5′-phosphorylated DNA at temperatures ranging from 75 to 99°C. The cleavage activity was regulated by the divalent cations Mn
2+
, Mg
2+
, Co
2+
, and Ni
2+
. In addition,
Fp
Ago possesses guide/target mismatch tolerance in the seed region but is sensitive to mismatches in the 3′-guide region. Notably, the EMSA assay revealed that the
Fp
Ago-guide-target ternary complex exhibited a stronger binding affinity for short 15 and 16 nt guide DNAs than longer guides. Moreover, we performed structural modeling analyses that implied the unique PAZ domain of
Fp
Ago for 3′-guide recognition and binding to affect guide length specificity. This study broadens our understanding of thermophilic Agos and paves the way for their use in DNA manipulation.
DNA phosphorothioate (PT) modification, with a nonbridging phosphate oxygen substituted by sulfur, represents a widespread epigenetic marker in prokaryotes and provides protection against genetic ...parasites. In the PT-based defense system Ssp, SspABCD confers a single-stranded PT modification of host DNA in the 5'-C
CA-3' motif and SspE impedes phage propagation. SspE relies on PT modification in host DNA to exert antiphage activity. Here, structural and biochemical analyses reveal that SspE is preferentially recruited to PT sites mediated by the joint action of its N-terminal domain (NTD) hydrophobic cavity and C-terminal domain (CTD) DNA binding region. PT recognition enlarges the GTP-binding pocket, thereby increasing GTP hydrolysis activity, which subsequently triggers a conformational switch of SspE from a closed to an open state. The closed-to-open transition promotes the dissociation of SspE from self PT-DNA and turns on the DNA nicking nuclease activity of CTD, enabling SspE to accomplish self-nonself discrimination and limit phage predation, even when only a small fraction of modifiable consensus sequences is PT-protected in a bacterial genome.
Rituximab has proven effective for the treatment of steroid‐refractory bullous pemphigoid (BP), but there is controversy over the dosing protocol. We report three cases of refractory BP treated ...successfully with ultra‐low‐dose rituximab (100 mg weekly for 4 weeks). Our cases confirmed the efficacy and good follow‐up outcomes of this treatment strategy for refractory BP. The ultra‐low‐dose rituximab regimen (100 mg weekly for 4 weeks) may be a useful alternative therapy in patients with refractory BP.
The endometrium and uterine junction zone often change throughout the menstrual cycle. Some pathological conditions may appear normal in uterine imaging, which will lead to missed diagnosis and ...misdiagnosis.
To evaluate the changes in the thickness and apparent diffusion coefficient (ADC) values of the endometrium and uterine junction zone throughout the menstrual cycle in magnetic resonance imaging (MRI) of women of reproductive age.
Data were collected from 40 healthy women of reproductive age with regular menstrual cycles from January 2017 to April 2018. They underwent four total MRI sessions during the menstrual, proliferation, and early and late secretive phases. The main MRI sequences were T2-weighted (T2W) volume isotropic turbo spin echo acquisition (VISTA) spectral attenuated inversion recovery (SPAIR) and diffusion-weighted imaging (b = 0, 600, 800, 1000 s/mm
), which were used to measure the thicknesses and ADC values of endometrium and uterine junction zone.
First, the endometrium was thinnest during the menstrual phase and thickest in the late secretive phase. Second, the uterine junction zone was thinnest in the late secretive phase and thickest in the menstrual phase. Third, the ADC values of the endometrium were lowest in the menstrual phase and peaked in the early secretive phase. Finally, the ADC values of the uterine junction zone were lowest in the menstrual phase and peaked in the late secretive phase.
The endometrium and uterine junction zone showed cyclic changes. Radiologists should consider these changes in the thickness and ADC values when analyzing MRI images of the uterus.
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