A randomized, double-blind, placebo-controlled phase II study to evaluate the efficacy and safety of ivarmacitinib (SHR0302) in adult patients with moderate-to-severe alopecia areata.

BACKGROUND: Alopecia areata (AA) is a CD8+ T cell-mediated autoimmune disease characterized by nonscarring hair loss. Ivarmacitinib, which is a selective oral Janus kinase 1 inhibitor, may interrupt certain cytokine signaling implicated in the pathogenesis of AA. OBJECTIVE: To evaluate the efficacy and safety of ivarmacitinib in adult patients with AA who have ≥25% scalp hair loss. METHODS: Eligible patients were randomized 1:1:1:1 to receive ivarmacitinib 2, 4, or 8 mg once daily or placebo for 24 weeks. The primary end point was the percentage change from baseline in the Severity of Alopecia Tool score at week 24. RESULTS: A total of 94 patients were randomized. At week 24, the least squares mean difference in the percentage change from baseline in the Severity of Alopecia Tool score for ivarmacitinib 2, 4, and 8 mg and placebo groups were -30.51% (90% CI, -45.25, -15.76), -56.11% (90% CI, -70.28, -41.95), -51.01% (90% CI, -65.20, -36.82), and -19.87% (90% CI, -33.99, -5.75), respectively. Two serious adverse events-follicular lymphoma and COVID-19 pneumonia-were reported. LIMITATIONS: A small sample size limits the generalizability of the results. CONCLUSION: Treatment with ivarmacitinib 4 and 8 mg doses in patients with moderate and severe AA for 24 weeks was efficacious and generally tolerated.

Physicochemical properties and fractal characterizations of the functionalized porous clinoptilolites for controlling alginate delivery in growing cauliflower and leaf mustard.

Using natural clinoptilolite (NCP) as a carrier and alginate (Alg)-calcium as an active species, the porous silicon calcium alginate nanocomposite (Alg-Ca-NCP) was successfully fabricated via adsorption-covalence-hydrogen bond. Its structural features and physicochemical properties were detailed investigated by various characterizations. The results indicated that Alg-Ca-NCP presented the disordered lamellar structures with approximately uniform particles in size of 300-500 nm. Specially, their surface fractal evolutions between the irregular roughness and dense structures were demonstrated via the SAXS patterns. The results elucidated that the abundant micropores of NCP were beneficial for unrestricted diffusing of Alg-Ca, which was conducive to facilitate a higher loading and sustainable releasing. The Ca content of leaf mustard treated with Alg-Ca-NCP-0.5 was 484.5 mg/100g on the 21st day, higher than that by water (CK) and CaCl2 solution treatments, respectively. Meanwhile, the prepared Alg-Ca-NCPs presented the obvious anti-aging effects on peroxidase drought stress of mustard leaves. These demonstrations provided a simple and effective method to synthesize Alg-Ca-NCPs as delivery nanocomposites, which is useful to improve the weak absorption and low utilization of calcium alginate by plants.

The enzymatic hydrolysate of fucoidan from Sargassum hemiphyllum triggers immunity in plants.

Fucoidans are polysaccharides that consist predominantly of sulfated L-fucoses, from which, fucoidan oligosaccharides (FOSs) are prepared through different methods. Fucoidan has versatile physiological activities, like antiviral functions against SARS CoV-2 and bioactivitiy in enhancing immune responses. Although fucoidan or FOS has been widely used in mammals as functional foods and new drugs, its application in plants is still very limited. Moreover, whether fucoidan or its derived hydrolytic products can trigger immune responses in plants remained unknown. In this work, we demonstrate that the fucoidan enzymatic hydrolysate (FEH) prepared from Sargassum hemiphyllum triggers various immune responses, such as ROS production, MAPK activation, gene expression reprogramming, callose deposition, stomatal closure, and plant resistance to the bacterial strain Pseudomonas syringae pv. tomato (Pst) DC3000. Notably, FEH did not induce Arabidopsis root growth inhibition at the concentration used for triggering other immune responses. Our work suggests that EHF can potentially be used as a non-microbial elicitor in agricultural practices to protect plants from pathogen infection.

Comparison of safety and efficacy between calcipotriol plus betamethasone dipropionate gel and calcipotriol scalp solution as long-term treatment for scalp psoriasis in Chinese patients: a national, multicentre, prospective, randomized, active-controlled phase 4 trial.

BACKGROUND: The efficacy and safety of calcipotriol plus betamethasone dipropionate gel for the treatment of scalp psoriasis has previously been demonstrated in a four-week trial in a Chinese population. OBJECTIVE: To evaluate the long-term safety and efficacy of two-compound gel in Chinese adult patients with scalp psoriasis. MATERIALS & METHODS: A multicentre, prospective, randomized, active-controlled trial was established in which subjects were randomized (at a ratio of 4:1) to receive either two-compound gel once daily or calcipotriol scalp solution twice daily for 28 weeks. Incidence of adverse drug reactions (ADRs) of any type and adverse events (AEs) of concern associated with long-term corticosteroid use on the scalp were evaluated. RESULTS: A total of 951 subjects were randomly assigned to receive either two-compound gel (n=760) or calcipotriol scalp solution (n=191). The incidence of ADRs was significantly lower in the two-compound gel group compared with the calcipotriol scalp solution group (11.7 vs. 22.2%, p<0.001). There was no significant difference in treatment-emergent adverse events (TEAEs) associated with long-term topical corticosteroid use on the scalp (1.1% vs. 0%, p=0.369) between the two groups. A statistically significant difference in the percentage of visits with treatment success according to the Subject's Global Assessment was observed (p=0.009); more subjects had visits with 100% treatment success (15.2 vs. 6.3%) and fewer subjects had visits with 0% treatment success (23.7 vs. 30.8%) using two-compound gel compared to calcipotriol scalp solution. CONCLUSION: The two-compound gel was well tolerated and effective in the long-term management of scalp psoriasis in Chinese patients.

A systematic review and meta-analysis of gastrointestinal events associated with nonoperative therapies for neuroendocrine tumors.

The risk of gastrointestinal (GI) events induced by nonoperative therapies in patients with neuroendocrine tumors (NETs) is unclear. Nonoperative therapies include somatostatin analogs, molecular targeted agents, cytotoxic chemotherapy, interferon-α, and peptide receptor radionuclide therapy. We undertook an up-to-date meta-analysis to determine the incidence and relative risks (RRs) of GI events in NET patients treated with these therapies. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched to identify relevant trials. Eligible trials were selected according to the PRISMA statement. Summary incidence, RR, and 95% CIs were calculated using random- and fixed-effects models. We included 2,890 patients from 17 randomized controlled trials in this meta-analysis. The experimental treatments led to increased incidence and risks of GI events compared to the control treatments (P<0.05). Diarrhea was the most common GI event. The experimental treatments were associated with increased risks of high-grade nausea (RR 2.36; 95% CI 1.05-5.25; P<0.01) and vomiting (RR 1.89; 95% CI 1.04-3.44; P<0.05). In regard to specific therapy regimens, everolimus led to increased risks of diarrhea (RR 2.97; 95% CI 1.83-4.83; P<0.05), vomiting (RR 2.19; 95% CI 1.38-3.48; P<0.05), and anorexia (RR 3.20; 95% CI 1.69-6.06; P<0.05), whereas VEGFR inhibitors led to increased risk of diarrhea (RR 2.12; 95% CI 1.39-3.25; P<0.05). Additionally, GI NETs led to higher risk of GI events than pancreatic NETs. Thus, nonoperative therapies are associated with increased risks of GI events in NET patients, and rigorous management is warranted to minimize the adverse impact on treatment outcomes and to improve quality of life.

Alginate-derived oligosaccharides promote water stress tolerance in cucumber (Cucumis sativus L.).

Marine alginate-derived oligosaccharides (ADOs) are prepared from degraded alginate. Our experiments were carried out to determine the mechanism of ADOs to improve resistance to water stress in cucumber (Cucumis sativus L.). We evaluated the effects of ADOs on physiological indices, photosynthesis, reactive oxygen species (ROS) levels, antioxidant enzyme activities, and relative expression levels of drought resistance genes. The growth of drought stressed cucumber decreased markedly. However, treatment with ADOs significantly improved the diameter, fresh weight, photosynthetic rate, transpiration rate, stomatal conductance, maximum quantum yield of photosystem II (Fv/Fm) and chlorophyll degradation; thus, reversing the effects of drought stress. Moreover, the antioxidant levels and ROS scavenging enzyme activities also increased in response to the ADOs. Additionally, the genes involved in abscisic aid (ABA) signaling and the drought stress response, such as superoxide dismutase [Cu-Zn] (CsSOD(Cu-Zn)), the peroxidase superfamily protein (CsPOD3), ABA deficient 2 (CsABA2), responsive to ABA 18 (CsRAB18), abscisic acid insensitive 5 (CsABI5), responsive to dehydration 22 (CsRD22), and responsive to dehydration 29A (CsRD29A) were upregulated by ADOs. The ABA content was also improved by ADOs. Our results suggest that ADOs induced the expression of some antioxidant enzyme synthetic genes involved in the ABA signaling pathway by stimulating ABA synthesis to improve the drought resistance capacity in cucumber.

Transient bullous dermolysis of the newborn: a novel de novo mutation in the COL7A1 gene.

BACKGROUND: Bullous dermolysis of the newborn (BDN), an extremely rare clinical type of dystrophic epidermolysis bullosa (DEB), is characterized by subepidermal blistering at birth or shortly thereafter, followed by rapid improvement with minimal scarring or pigmentation. A total of 38 cases have been reported in the literature since the disease was initially described in 1985, but only 14 mutations in COL7A1, the gene responsible for the disease, have been detected in families with BDN. OBJECTIVES: We report a Chinese male infant with BDN and indirect inguinal hernia, in whom a novel de novo mutation in COL7A1 was demonstrated. METHODS: DNA was obtained from the blood of the patient and his parents. The coding exon and flanking regions of COL7A1 gene were amplified by polymerase chain reaction and subjected to sequence analysis. RESULTS: Sequencing showed a heterozygous substitution of guanine by adenine at nucleotide position 6136 of exon 73 in the triple helical domain of type VII collagen, which predicts a change of glycine by serine at position p.G2046S. The mutation was considered to be a pathogenic and de novo mutation. CONCLUSIONS: The coexistence of BDN and indirect inguinal hernia may simply be coincidental. These data contribute to the expanding database of COL7A1 mutations in DEB and should be useful for genetic counseling and prenatal diagnosis in affected families.