BACKGROUND: Enhancing blood flow and cell proliferation in the hair dermis is critical for treating hair loss. This study was designed to aid the development of alternative and effective solutions to overcome alopecia. Specifically, we examined the effects of Morus alba.L root extract (MARE, which has been used in traditional medicine as a stimulant for hair proliferation) on dermal fibroblasts and other cell types found in the epidermis. METHODS: We first optimized the concentration of MARE that could be used to treat human dermal fibroblasts (HDFs) without causing cytotoxicity. After optimization, we focused on the effect of MARE on HDFs since these cells secrete paracrine factors related to cell proliferation and angiogenesis that affect hair growth. Conditioned medium (CM) derived from MARE-treated HDFs (MARE HDF-CM) was used to treat human umbilical vein endothelial cells (HUVECs) and hair follicle dermal papilla cells (HFDPCs). RESULTS: Concentrations of MARE up to 20 wt% increased the expression of proliferative and anti-apoptotic genes in HDFs. MARE HDF-CM significantly improved the tubular structure formation and migration capacity of HUVECs. Additionally, MARE HDF-CM treatment upregulated the expression of hair growth-related genes in HFDPCs. CM collected from MARE-treated HDFs promoted the proliferation of HFDPCs and the secretion of angiogenic paracrine factors from these cells. CONCLUSION Since it can stimulate the secretion of pro-proliferative and pro-angiogenic paracrine factors from HDFs, MARE has therapeutic potential as a hair loss preventative.

Gut microbiota produce dietary metabolites such as short-chain fatty acids, which exhibit anti-inflammatory effects. Free fatty acid receptor 2 (FFA2, formerly known as GPR43) is a specific receptor for short-chain fatty acids, such as acetate that regulates inflammatory responses. However, the therapeutic potential of FFA2 agonists for treatment of atopic dermatitis has not been investigated. We investigated the efficacy of the FFA2 agonist, 4-chloro-α-(1-methylethyl)-N-2-thiazoylylbenzeneacetanilide (4-CMTB), for treatment of atopic dermatitis induced by 2,4-dinitrochlorobenzene (DNCB). Long-term application of DNCB to the ears of mice resulted in significantly increased IgE in the serum, and induced atopic dermatitis-like skin lesions, characterized by mast cell accumulation and skin tissue hypertrophy. Treatment with 4-CMTB (10 mg/kg, i.p.) significantly suppressed DNCB-induced changes in IgE levels, ear skin hypertrophy, and mast cell accumulation. Treatment with 4-CMTB reduced DNCB-induced increases in Th2 cytokine (IL-4 and IL-13) levels in the ears, but did not alter Th1 or Th17 cytokine (IFN-γ and IL-17) levels. Furthermore, 4-CMTB blocked DNCB-induced lymph node enlargement. In conclusion, activation of FFA2 ameliorated DNCB-induced atopic dermatitis, which suggested that FFA2 is a therapeutic target for atopic dermatitis.

Sphingosine-1-phosphate (S1P) and its receptors have been implicated in atopic dermatitis. S1P2 was found to function as a proallergic receptor, while its antagonist JTE-013 was found to suppress allergic asthma in mice. Topical application of JTE-013 has not been investigated in an in vivo model of atopic dermatitis. Therefore, the therapeutic potential of JTE-013 topical application was evaluated by the use of a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model. DNCB-induced inflammation and mast cell accumulation in skin tissues were significantly suppressed by topical JTE-013 treatment in BALB/c mice. DNCB-induced increase of lymph nodes sizes and elevated inflammatory cytokines (IL-4, IL-13, IL-17, and IFN-γ) in lymph nodes were also significantly reduced by the JTE-013 treatment. Elevated serum levels of IgE were significantly suppressed by the topical treatment of JTE-013. In summary, the topical treatment of JTE-013 S1P2antagonist suppressed DNCB-induced atopic dermatitis symptoms and immune responses. These results suggested JTE-013 as a potential therapeutic agent for atopic dermatitis.

A 74-year-old woman presented with a progressive pattern of dysphagia and odynophagia over one month.Magnetic resonance imaging of the neck revealed diffuse swelling from the tongue base and velum extending to the posterior pharyngeal wall. Instrumental evaluation of swallowing showed decreased peristalsis in the esophageal phase, accompanied by severe swelling of the hypopharynx, which limited laryngeal elevation and subsequently led to decreased bolus clearance and impaired airway protection. Laboratory studies revealed a 61% increase in eosinophil count. An endoscopic biopsy of the esophagus confirmed the diagnosis of eosinophilic esophagitis. The patient was administered intravenous dexamethasone at a total dosage of 45 mg/day for 7 days. The eosinophil count dropped to the normal range, correlating with the improvement in dysphagia and aspiration. Eosinophilic esophagitis often presents in children and rarely involves the oropharyngeal structures. Due to its specific involvement of the esophagus, it seldom leads to aspiration. By contrast, the extension of eosinophilic inflammation from the esophagus to the oropharynx in this case resulted in atypical symptoms such as odynophagia and aspiration. The therapeutic approach can be challenging due to the difficulty in administering topical steroids, which are often the treatment of choice. However, the condition showed an excellent response to intravenous steroid therapy.

A 74-year-old woman presented with a progressive pattern of dysphagia and odynophagia over one month.Magnetic resonance imaging of the neck revealed diffuse swelling from the tongue base and velum extending to the posterior pharyngeal wall. Instrumental evaluation of swallowing showed decreased peristalsis in the esophageal phase, accompanied by severe swelling of the hypopharynx, which limited laryngeal elevation and subsequently led to decreased bolus clearance and impaired airway protection. Laboratory studies revealed a 61% increase in eosinophil count. An endoscopic biopsy of the esophagus confirmed the diagnosis of eosinophilic esophagitis. The patient was administered intravenous dexamethasone at a total dosage of 45 mg/day for 7 days. The eosinophil count dropped to the normal range, correlating with the improvement in dysphagia and aspiration. Eosinophilic esophagitis often presents in children and rarely involves the oropharyngeal structures. Due to its specific involvement of the esophagus, it seldom leads to aspiration. By contrast, the extension of eosinophilic inflammation from the esophagus to the oropharynx in this case resulted in atypical symptoms such as odynophagia and aspiration. The therapeutic approach can be challenging due to the difficulty in administering topical steroids, which are often the treatment of choice. However, the condition showed an excellent response to intravenous steroid therapy.

A 74-year-old woman presented with a progressive pattern of dysphagia and odynophagia over one month.Magnetic resonance imaging of the neck revealed diffuse swelling from the tongue base and velum extending to the posterior pharyngeal wall. Instrumental evaluation of swallowing showed decreased peristalsis in the esophageal phase, accompanied by severe swelling of the hypopharynx, which limited laryngeal elevation and subsequently led to decreased bolus clearance and impaired airway protection. Laboratory studies revealed a 61% increase in eosinophil count. An endoscopic biopsy of the esophagus confirmed the diagnosis of eosinophilic esophagitis. The patient was administered intravenous dexamethasone at a total dosage of 45 mg/day for 7 days. The eosinophil count dropped to the normal range, correlating with the improvement in dysphagia and aspiration. Eosinophilic esophagitis often presents in children and rarely involves the oropharyngeal structures. Due to its specific involvement of the esophagus, it seldom leads to aspiration. By contrast, the extension of eosinophilic inflammation from the esophagus to the oropharynx in this case resulted in atypical symptoms such as odynophagia and aspiration. The therapeutic approach can be challenging due to the difficulty in administering topical steroids, which are often the treatment of choice. However, the condition showed an excellent response to intravenous steroid therapy.

Autoimmune pancreatitis (AIP) is rarely associated with pancreatic pseudocysts. AIP-associated pseudocysts requiring drainage despite steroid therapy are rather rare. We report a case of AIP with an infected pseudocyst requiring drainage despite steroid therapy. A 68-year-old male was diagnosed with AIP via pancreatic imaging, a high serum immunoglobulin G4 level, and steroid responsiveness. The AIP was accompanied by a pancreatic pseudocyst. Steroid therapy was prescribed, but the pancreatic pseudocyst became aggravated during steroid tapering. Endoscopic ultrasonography-guided cyst drainage was required; the pseudocyst then became completely resolved.
Aged ; Drainage* ; Humans ; Immunoglobulins ; Male ; Pancreatic Pseudocyst ; Pancreatitis* ; Steroids

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.