The role of BAFF and BAFF-R inhibitors in the treatment of immune thrombocytopenia; a focused review.

Immune thrombocytopenia (ITP) is an autoimmune-driven disease characterized by increased destruction and impaired platelet production resulting in an enhanced risk of bleeding. Immunosuppressant agents are the most common treatment strategies for ITP. Despite their efficacy, these medications often cause unpredictable side effects. Recent investigations revealed that patients with ITP exhibit elevated B-cell activating factor (BAFF) levels in both their spleens and serum. Belimumab, a BAFF inhibitor, illustrated a promising therapeutic avenue for managing ITP by interfering with BAFF activity and long-lived plasma cell production. Both clinical and experimental studies have yielded positive outcomes when combining rituximab with an anti-BAFF monoclonal antibody in treating ITP. In addition, ianalumab, a monoclonal antibody with a dual mechanism that targets BAFF-R and deletes peripheral BAFF-R+ B cells, is currently being used for ITP treatment [NCT05885555]. The upcoming results from novel BAFF inhibitors, such as ianalumab, could offer clinicians an additional therapeutic option for treating ITP.

Alcohol: Epigenome alteration and inter/transgenerational effect.

While DNA serves as the fundamental genetic blueprint for an organism, it is not a static entity. Gene expression, the process by which genetic information is utilized to create functional products like proteins, can be modulated by a diverse range of environmental factors. Epigenetic mechanisms, including DNA methylation, histone modification, and microRNAs, play a pivotal role in mediating the intricate interplay between the environment and gene expression. Intriguingly, alterations in the epigenome have the potential to be inherited across generations. Alcohol use disorder (AUD) poses significant health issues worldwide. Alcohol has the capability to induce changes in the epigenome, which can be inherited by offspring, thus impacting them even in the absence of direct alcohol exposure. This review delves into the impact of alcohol on the epigenome, examining how its effects vary based on factors such as the age of exposure (adolescence or adulthood), the duration of exposure (chronic or acute), and the specific sample collected (brain, blood, or sperm). The literature underscores that alcohol exposure can elicit diverse effects on the epigenome during different life stages. Furthermore, compelling evidence from human and animal studies demonstrates that alcohol induces alterations in epigenome content, affecting both the brain and blood. Notably, rodent studies suggest that these epigenetic changes can result in lasting phenotype alterations that extend across at least two generations. In conclusion, the comprehensive literature analysis supports the notion that alcohol exposure induces lasting epigenetic alterations, influencing the behavior and health of future generations. This knowledge emphasizes the significance of addressing the potential transgenerational effects of alcohol and highlights the importance of preventive measures to minimize the adverse impact on offspring.

A systematic review of interleukin-31 inhibitors in the treatment of prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a neuroimmunological skin disease. Severe itching is the most challenging symptom which affects patients' quality of life. T helper 2-derived cytokines, such as interleukin-31 and oncostatin M (OSM), play a crucial role in PN pathogenesis. Nemolizumab and vixarelimab are two biologics acting as IL-31 inhibitors. Vixarelimab also suppresses the OSM activity. This systematic review evaluates the efficacy and safety of nemolizumab and vixarelimab in PN management. METHODS: A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science up to September 17th, 2023. Clinical trials and cohort studies published in English were included. RESULTS: Among a total of 96 relevant records, five were included. The results of four studies with 452 patients using nemolizumab showed that a significantly higher percentage of patients treated with nemolizumab demonstrated a reduction in peak pruritus numerical rating scale (PP-NRS) and investigator's global assessment along with improved sleep disturbance (SD) and quality of life than the placebo group. Moreover, one study administered vixarelimab to 49 PN patients, and their finding illustrated a higher rate of subjects who received vixarelimab experienced ≥ 4-point diminution in worst itch NRS, visual analog scale, healing of representative lesions, and SD quality compared to the placebo group. CONCLUSIONS: IL-31 inhibitors suggest distinct advantages in improving pruritus, sleep quality, and overall quality of life in subjects with moderate-to-severe PN. Further clinical studies are recommended to compare the effectiveness of these biologics to other therapeutic choices.

Efficacy and safety of lasers versus topical medications for acanthosis nigricans and pseudo-acanthosis nigricans treatment: a systematic review.

Acanthosis nigricans (AN) is a cutaneous disorder identified by well-defined pigmented plaques mostly detected on skin folds. Timely diagnosis and treatment of AN is essential as it could be an early manifestation of an underlying condition. The treatment of choice for AN has not been determined yet. Our study aimed to compare the efficacy and safety of various lasers with topical medications, including cream and peel. PubMed, Scopus, and Web of Science databases, as well as the Google Scholar search engine, were thoroughly searched until May 1st, 2023. Study selection was restricted to clinical trials published in English language comparing lasers with topical treatments. This study followed the PRISMA guidelines for systematic reviews and meta-analyses. Out of 1748 studies, Six clinical trials met our inclusion criteria, with 133 patients. We examined laser therapies, including fractional CO2 laser, 1550-nm erbium fiber laser, and long-pulsed alexandrite laser, while the topical treatments comprised glycolic acid (GA) peel, retinoic acid peel, trichloroacetic acid (TCA) peel, and tretinoin cream. In two studies, GA peel demonstrated favorable results compared to fractional CO2 laser. Besides, fractional CO2 laser exhibited efficacy, surpassing TCA peel in AN management. Additionally, a fractional 1550-nm erbium fiber laser displayed superiority over tretinoin cream in reducing average roughness. Similarly, a long-pulsed alexandrite laser demonstrated its effectiveness in axillary AN treatment compared to the combination of tretinoin and ammonium lactate. Overall, the findings revealed that laser therapy was associated with superior results. Moreover, topical treatments are safe and efficacious in AN management.

Autologous adipose tissue injection in the treatment of alopecia: A mini-review.

BACKGROUND: Alopecia may decrease patients' quality of life and self-confidence by limiting their social life. Therefore, the main goal of the treatment is to limit or halt the progression of inflammation, scarring, and hair loss. The promising effect of fat injection on hair regrowth, limited adverse effects, and subsiding inflammation can be proof of its efficacy and safety in treating alopecia. AIMS: This review sought to assess the role of autologous fat tissue injection in scarring and non-scarring alopecia. METHODS: Accordingly, a thorough search was performed on the Web of Science, Scopus, and PubMed/Medline databases, as well as the Google Scholar search engine, for studies published from inception until September 1st, 2023, using the related keywords. RESULTS: Autologous fat grafting (AFG) is a novel and potentially effective modality for treating alopecia, particularly primary and secondary cicatricial alopecia. AFG can be an effective semi-invasive option for treating refractory lichen planopilaris because it induces angiogenesis, which supports hair regrowth. In addition to cicatricial alopecia, AFG held promise for treating non-scarring alopecia, including androgenic alopecia and alopecia areata. The adipose-derived regenerative cells (ADRCs) in adipose tissue (AT) secrete different growth factors, further supporting hair regeneration. Moreover, different anti-inflammatory and anti-oxidative agents are known in AT, preventing further damage to hair follicles. CONCLUSIONS: AFG can significantly control inflammatory processes, improve signs and symptoms, and increase hair density and diameter.

A systematic review of Janus kinase inhibitors and spleen tyrosine kinase inhibitors for Hidradenitis suppurativa treatment.

BACKGROUNDS AND AIMS: Hidradenitis suppurativa (HS) is a challenging skin disease with an underlying inflammatory process. Substantial progress has been made in our understanding of HS over the last few years, with the advancement of novel treatment approaches. The current systematic review aims to evaluate the safety and efficacy of Janus kinase (JAK) inhibitors and spleen tyrosine kinase (Syk) inhibitors in treating HS. METHOD: A thorough systematic search was performed on PubMed/Medline, Web of Science, and Ovid Embase databases up to September 23th, 2023. Clinical studies published in English were included. RESULTS: Our search yielded ten articles with a total of 165 patients treated with four types of JAK inhibitors (upadacitinib, povorcitinib, tofacitinib, and baricitinib) and one Syk inhibitor (fostamatinib). Upadacitinib, povorcitinib, and tofacitinib improved clinical outcomes, with a significant reduction in hidradenitis suppurativa clinical response (HiSCR) and abscess and inflammatory nodule count (AN count) during the treatment period. Also, these drugs are well tolerated in most HS patients with minimal adverse events (AEs). Moreover, baricitinib depicted an amelioration in signs and symptoms of HS in one case report. Also, fostamatinib exhibited favorable tolerability throughout a 12-week in moderate-to-severe HS patients. The remarkable clinical improvement, as assessed through HiSCR and hidradenitis suppurativa severity (IHS4), corresponded closely with serological indicators of inflammation following fostamatinib administration was achieved. CONCLUSION: JAK and Syk inhibitors are potentially efficacious in managing moderate-to-severe HS since the proinflammatory cytokines are mediated by JAK and Syk signaling pathways. However, further research with a more rigorous examination is mandatory to evaluate such medication's long-term safety and efficacy.

Efficacy and safety of Bruton's tyrosine kinase inhibitors in the treatment of pemphigus: A comprehensive literature review and future perspective.

Bruton's tyrosine kinase (BTK) is a protein involved in B-cell-receptor signaling and B-cell proliferation. The pathophysiology of several autoimmune diseases, such as pemphigus disorder, relies on the BTK signaling pathway. Therefore, BTK inhibitors were found to be beneficial alternatives to conventional treatmentsThe current study aimed to assess the efficacy and safety of BTK inhibitors in treating pemphigus. A complete search was performed on databases including PubMed/MedLine, Scopus, Web of Science, as well as Google Scholar search engine for studies published by September 20th, 2023. The current review indicates that BTK inhibitors alone or in combination with conventional treatments are promising options in the management of pemphigus. The overall safety profile of BTK inhibitors has been acceptable, and the reported adverse reactions were not severe or life-threatening.

Association between metabolic syndrome and prevalent skin diseases: A systematic review and meta-analysis of case-control studies.

Background and Aim: Metabolic syndrome (MetS) is a well-known noncommunicable disease that plays a significant role in emerging other chronic disorders and following complications. MetS is also involved in the pathophysiology of numerous dermatological diseases. We aim to evaluate the association of MetS with the most prevalent dermatological diseases. Methods: A systematic search was carried out on PubMed, Science Direct, Web of Science, Cochrane, as well as the Google Scholar search engine. Only English case-control studies regarding MetS and any skin disease from the beginning of 2010 up to November 15, 2022, were selected. The study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Results: A total of 37 studies (13,830 participants) met the inclusion criteria. According to our result, patients with psoriasis, hidradenitis suppurativa (HS), vitiligo, androgenetic alopecia (AGA), and lichen planus (LP) have a higher chance of having MetS compared to the general population. Furthermore, people with seborrheic dermatitis (SED) and rosacea are more prone to insulin resistance, high blood pressure (BP), and higher blood lipids. After pooling data, the meta-analysis revealed a significant association between MetS and skin diseases (pooled odds ratio [OR]: 3.28, 95% confidence interval: 2.62-4.10). Concerning the type of disease, MetS has been correlated with AGA (OR: 11.86), HS (OR: 4.46), LP (OR: 3.79), and SED (OR: 2.45). Psoriasis also showed a significant association but with high heterogeneity (OR: 2.89). Moreover, skin diseases and MetS are strongly associated in Spain (OR: 5.25) and Thailand (OR: 11.86). Regarding the metaregression model, the effect size was reduced with increasing age (OR: 0.965), while the size increased with AGA (OR: 3.064). Conclusions: MetS is closely associated with skin complications. Dermatologists and other multidisciplinary teams should be cautious while treating these patients to prevent severe complications resulting from MetS.

Microfluidic Synthesis of Ultrasmall Chitosan/Graphene Quantum Dots Particles for Intranasal Delivery in Alzheimer's Disease Treatment.

Nanoparticles (NPs) based therapies for Alzheimer's disease (AD) attract interest due to their ability to pass across or bypass the blood-brain barrier. Chitosan (CS) NPs or graphene quantum dots (GQDs) are promising drug carriers with excellent physicochemical and electrical properties. The current study proposes the combination of CS and GQDs in ultrasmall NP form not as drug carriers but as theranostic agents for AD. The microfluidic-based synthesis of the CS/GQD NPs with optimized characteristics makes them ideal for transcellular transfer and brain targeting after intranasal (IN) delivery. The NPs have the ability to enter the cytoplasm of C6 glioma cells in vitro and show dose and time-dependent effects on the viability of the cells. IN administration of the NPs to streptozotocin (STZ) induced AD-like models lead to a significant number of entrances of the treated rats to the target arm in the radial arm water maze (RAWM) test. It shows the positive effect of the NPs on the memory recovery of the treated rats. The NPs are detectable in the brain via in vivo bioimaging due to GQDs as diagnostic markers. The noncytotoxic NPs localize in the myelinated axons of hippocampal neurons. They do not affect the clearance of amyloid ß (Aß) plaques at intercellular space. Moreover, they showed no positive impact on the enhancement of MAP2 and NeuN expression as markers of neural regeneration. The memory improvement in treated AD rats may be due to neuroprotection via the anti-inflammation effect and regulation of the brain tissue microenvironment that needs to be studied.

Brain Homogenate of a Rat Model of Alzheimer's Disease Modifies the Secretome of 3D Cultured Periodontal Ligament Stem Cells: A Potential Neuroregenerative Therapy.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease leading to neuronal cell death and manifested by cognitive disorders and behavioral impairment. Mesenchymal stem cells (MSCs) are one of the most promising candidates to stimulate neuroregeneration and prevent disease progression. Optimization of MSC culturing protocols is a key strategy to increase the therapeutic potential of the secretome. Objectives: Here, we investigated the effect of brain homogenate of a rat model of AD (BH-AD) on the enhancement of protein secretion in the secretome of periodontal ligament stem cells (PDLSCs) when cultured in a 3D environment. Moreover, the effect of this modified secretome was examined on neural cells to study the impact of the conditioned medium (CM) on stimulation of regeneration or immunomodulation in AD. Methods: PDLSCs were isolated and characterized. Then, the spheroids of PDLSCs were generated in a modified 3D culture plate. PDLSCs-derived CM was prepared in the presence of BH-AD (PDLSCs-HCM) and the absence of it (PDLSCs-CM). The viability of C6 glioma cells was assessed after exposure to different concentrations of both CMs. Then, a proteomic analysis was performed on the CMs. Results: Differentiation into adipocytes and high expression of MSCs markers verified the precise isolation of PDLSCs. The PDLSC spheroids were formed after 7 days of 3D culturing, and their viability was confirmed. The effect of CMs on C6 glioma cell viability showed that both CMs at low concentrations (> 20 mg/mL) had no cytotoxic effect on C6 neural cells. The results showed that PDLSCs-HCM contains higher concentrations of proteins compared to PDLSCs-CM, including Src-homology 2 domain (SH2)-containing PTPs (SHP-1) and muscle glycogen phosphorylase (PYGM) proteins. SHP-1 has a role in nerve regeneration, and PYGM is involved in glycogen metabolism. Conclusions: The modified secretome derived from 3D cultured spheroids of PDLSCs treated by BH-AD as a reservoir of regenerating neural factors can serve as a potential source for AD treatment.