Principles and Clinical Application of Free-Style Capillary Perforator-Based Flap for Coverage of Facial Skin Cancer Defects.

This study introduces a free-style perforator based island flap (PBIF) for the reconstruction of skin defects. From March 2012 to December 2022, a retrospective investigation was conducted on patients who underwent reconstruction for facial defects due to skin cancer. Data on the patients' gender, age, anesthesia method, diagnosis, defect location, flap size, complications, and follow-up periods were collected. There are several principles for designing the PBIF: finger-pinching method, alignment with the direction of wrinkles, the smaller width and longer length of the flap, and proximal attachment to the muscle. A total of 32 patients were included, with an average age of 63.6 years. Surgeries were performed in various regions, such as the infraorbital area, nose, cheek, philtrum, and the anterior/posterior/inferior auricular regions, with an average flap size of 7.63 cm2. There were no complications, such as venous congestion or vascular insufficiency in the skin flaps, although one case required revisional closure due to flap disruption. The PBIF is a useful and effective method for the restoration of facial defects. This method can provide simple yet aesthetically satisfying results, showing stable outcomes without complex surgeries or complications. This study indicates the potential for this method to be more widely employed in reconstructive surgeries in the future.

Outcomes and Complications of Sole Reconstruction Using Lateral Thoracic Free Tissue Transfer.

BACKGROUND: The complex structure of the sole of the foot makes the repair of extensive defects challenging. The present study, therefore, aimed to address a gap in current research by evaluating the potential of the lateral thoracic free flap, including perforator options and chimeric configurations, to be used as an advanced solution for comprehensive sole reconstruction. PATIENTS AND METHODS: We retrospectively collected the following data from the charts of patients with sole defects, due to various causes, who underwent lateral thoracic free tissue transfers: patient demographics; etiologies; comorbidities; flap types and dimensions; pedicle length; operative time; follow-up period; complications; and management. RESULTS: The present study included 54 patients who underwent lateral thoracic free tissue transfer, citing infection, trauma, tumor, and posttraumatic sequelae as the major etiologies. We used the following techniques for the reconstruction of sole defects: thoracodorsal artery perforator free flap (83.3%); latissimus dorsi musculocutaneous free flap (1.9%); and various chimeric pattern flaps (14.8%). Free tissue transfer in the lateral thoracic region offers versatility for reconstruction, as well as low donor site morbidity. Complications observed in the present study included wound dehiscence (9.3%), partial necrosis (9.3%), and pressure ulcers (22.2%), although most patients healed favorably without flap loss. CONCLUSIONS: The lateral thoracic free flap is a viable option for the reconstruction of the sole of the foot and allows for the effective reconstruction of complex defects. It contains a sustainable skin paddle, and multiple components can be easily included as a chimeric type. Further studies should seek to identify ways to prevent pressure ulcers, which was the only known long-term complication in the present study.

Analysis of Operation Duration in Thoracodorsal Artery Perforator Free-Flap Surgery of the Lower Extremities.

PURPOSE: This retrospective study aimed to identify the factors that affect the duration of thoracodorsal artery perforator (TDAP) free-flap surgery and to offer strategies for optimizing the surgical procedure. METHODS: We analyzed 80 TDAP flap surgeries performed by a single surgeon between January 2020 and December 2022, specifically focusing on free flaps used for lower-extremity defects with single-artery and single-vein anastomosis. The operation duration was defined as the time between the surgeon's initial incision and completion of reconstruction. Linear regression analyses were conducted to identify the factors affecting operation duration. RESULTS: The average operative duration was 149 minutes (range, 80-245 minutes). All flaps survived, although 8 patients experienced partial flap loss. The operative duration decreased with increasing patient age and when end-to-end arterial anastomosis was performed. However, the risk increased with larger flap sizes and in patients with end-stage renal disease. CONCLUSIONS: Our study identified several factors and methods that could accelerate TDAP free-flap procedures. These findings offer valuable insights for optimizing surgical processes and improving overall surgical outcomes. Although further research is needed to confirm and expand upon these findings, our study provides important guidance for surgeons in developing effective strategies for TDAP flap surgery.

Isobavachin, a main bioavailable compound in Psoralea corylifolia, alleviates lipopolysaccharide-induced inflammatory responses in macrophages and zebrafish by suppressing the MAPK and NF-κB signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia L. (PC) is widely used in traditional medicines to treat inflammatory and infectious diseases. Isobavachin (IBC) is a bioavailable prenylated flavonoid derived from PC that has various biological properties. However, little information is available on its anti-inflammatory effects and mechanisms of action. AIM OF THE STUDY: In this study, we aimed to determine the anti-inflammatory effects of IBC in vitro and in vivo by conducting a mechanistic study using murine macrophages. MATERIALS AND METHODS: We evaluated the modulatory effects of IBC on the production of pro-inflammatory cytokines and mediators in murine macrophages. In addition, we examined whether IBC inhibits lipopolysaccharide (LPS)-induced inflammatory responses in a zebrafish model. Alterations in inflammatory response-associated genes and proteins were determined using quantitative reverse transcriptional polymerase chain reaction (RT-qPCR) and Western blotting analysis. RESULTS: IBC markedly reduced the overproduction of inflammatory mediators, pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear translocation of nuclear factor-kappa B (NF-κB) in macrophages induced by lipopolysaccharides (LPS). In addition, excessive NO, ROS, and neutrophil level induced by LPS, were suppressed by IBC treatment in a zebrafish inflammation model. CONCLUSIONS: Collectively, bioavailable IBC inhibited on the inflammatory responses by LPS via MAPK and NF-κB signaling pathways in vitro and in vivo, suggesting that it may be a potential modulatory agent against inflammatory disorders.

Anti-Osteoporotic Potential of Water Extract of Anethum graveolens L. Seeds.

Anethum graveolens L., known as European dill, is a versatile herb widely used in both traditional medicine and culinary practices. Despite its long-standing history, the potential impact of the water extract of A. graveolens seeds (WEAG) on bone health remains unexplored. In this study, we investigated the influence of WEAG on osteoclast differentiation and assessed its potential as an anti-osteoporotic agent. WEAG hindered osteoclast differentiation through the suppression of receptor activator of nuclear factor-κB ligand (RANKL) expression in osteoclast-supporting cells and by directly targeting osteoclast precursor cells. WEAG significantly reduced the expression of key osteoclastogenic transcription factors, namely c-Fos and NFATc1, typically induced by RANKL in osteoclast precursors. This reduction was attributed to the suppression of both MAPKs and NF-κB pathways in response to RANKL. In vivo experiments further revealed that WEAG administration effectively reduces trabecular bone loss and weight gain triggered by ovariectomy, mimicking postmenopausal osteoporosis. Furthermore, our comprehensive phytochemical analysis of WEAG identified a range of phytochemical constituents, associated with bone health and weight regulation. Notably, we discovered a specific compound, isorhamnetin-3-O-glucuronide, within WEAG that exhibits anti-osteoclastogenic potential. Overall, this research elucidated the beneficial effects and mechanistic basis of WEAG on osteoclast differentiation and bone loss, indicating its potential as a viable alternative to address bone loss in conditions like postmenopause.

Water Extract of Angelica dahurica Inhibits Osteoclast Differentiation and Bone Loss.

Angelica dahurica radix has a long history of traditional use in China and Korea for treating headaches, cold-damp pain and skin diseases. Despite various pharmacological studies on A. dahurica, its impact on bones remains unclear. Hence, this study investigated the inhibitory effect of A. dahurica's radix water extract (WEAD) on osteoclast differentiation. In vitro experiments showed that WEAD effectively suppresses osteoclast differentiation. Treatment of an osteoclast precursor with WEAD significantly suppressed the expression of nuclear factor of activated T-cells 1 (NFATc1), essential transcription factor for osteoclastogenesis, while increasing the expression of negative regulators, interferon regulatory factor 8 (Irf8) and v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MafB). Consistent with the in vitro findings, the oral administration of WEAD (100 and 300 mg/kg/day) to mice subjected to surgical ovariectomy for a duration of six weeks alleviated bone loss, while also mitigating weight gain and liver fat accumulation. In addition, we also identified phytochemicals present in WEAD, known to regulate osteoclastogenesis and/or bone loss. These results suggest the potential use of WEAD for treating various bone disorders caused by excessive bone resorption.

Reconstruction of a Severe Open Tibiofibular Fracture using an Ipsilateral Vascularized Fractured Fibula with a Thoracodorsal Artery Perforator Free Flap.

The Gustilo IIIB tibiofibular fractures often result in long bone loss and extensive soft tissue defects. Reconstruction of these complex wounds is very challenging, especially when it includes long bone grafts, because the donor site is limited. We describe our experience using a set of chimeric ipsilateral vascularized fibula grafts with a thoracodorsal artery perforator free flap to reconstruct the traumatic tibia defects. A 66-year-old male suffered a severe comminuted tibia fracture and segmented fibula fracture with large soft tissue defects as a result of a traffic accident. He also had an open calcaneal fracture with soft tissue defects on the ipsilateral side. All the main vessels of the lower extremity were intact, and the cortical bone defect of the tibia was almost as large as the fractured fibula segment. We used an ipsilateral vascularized fibula graft to reconstruct the tibia and a thoracodorsal artery perforator flap to resurface the soft tissue, using the distal ends of peroneal vessels as named into sequential chimeric flaps. After 3 weeks, the calcaneal defect was reconstructed with second thoracodorsal artery perforator free flap. Reconstruction was successful and allowed rapid rehabilitation because of reduced donor site morbidity.

A modified induced membrane 2-stage technique using a thoracodorsal artery perforator free flap followed by vascularized or non-vascularized free fibular transfer for the treatment of complex bone infection with concomitant severe soft tissue lesion-A case series of 9 cases.

Treatment of post-traumatic complex bone infection is very challenging. The two principal bone reconstruction approaches are the single-stage vascularized bone graft technique and the two-stage induced membrane technique (IMT). Here we introduce a modified 2-stage induced membrane technique (MIMT) for complex long bone infection with a major bone defect and a concomitant severe soft tissue lesion. The 2-stage procedure consists of bone debridement, placement of a PMMA spacer and soft tissue reconstruction with a thoracodorsal artery perforator free flap ("Tdap") at stage 1. At stage 2, the thoracodorsal artery perforator flap is elevated and a fibular strut graft (either vascularized of non-vascularized) is placed for bone reconstruction. We retrospectively analyzed the extents of lower extremity, long bone, post-traumatic bone infection treated via MIMT from 2008 to 2020. There were nine such cases (eight males) of mean age 59.8 (range 31 to 79) years. The osteomyelitis durations ranged from 3 to 360 months (mean 53 months). The cortical bone defect sizes was ranged from 9 to 14 cm (mean10.7 cm). All skin resurfacing employed Tdap. Vascularized fibular grafts were placed in six patients and non-vascularized grafts were placed in three. The fibular graft size ranged from 12.5 to 19 cm (mean 16.2 cm). Non-vascularized iliac bone grafts served as the fibula docking sites. Unfortunately, all patients suffered complications before bone union was achieved. One case of plate stress fracture and one case of screw fracture required plate and screw change. In three cases of cellulitis, one resolved by use of intravenous antibiotics, others required plate and screw removal. Wound disruption required re-suture and distal skin flap partial necrosis was covered by perforator-based island flap. One case of fibular stress fracture needed cast for 4 weeks. A peroneal nerve palsy patient recovered spontaneously. Bone union was achieved after 6 months in five patients and after 8 months in three (mean 6.9 months). All patients were able to walk unaided. The follow-up period ranged from 2 to 14 years (mean 6.2 years). MIMT saves the limbs in cases with difficult post-traumatic bone infection. It is valid treatment option for complex bone infections with severe soft tissue lesions. However, even with this technique potential complication must be considered.

Fingertip coverage with uni-pedicled volar rotational advancement flap with large Z-plasty: a report on 112 cases.

BACKGROUND: Simple and safe fingertip reconstruction methods involve the use of local neurovascular islands flaps that can preserve functional length and sensitivity, and reconstruction with skin of the same texture. However, techniques involving flaps have numerous drawbacks and do not satisfy all the requirements for fingertip reconstruction. A particular problem is the persistence of contracture deformity due to lack of full flap advancement. We present a new technique using uni-pedicled volar rotational advancement flap with large Z-plasty, and describe the results of long-term follow-up. METHODS: From October 1993 to December 2009, 112 fingers of 98 patients were covered with uni-pedicled volar rotational advancement flap with large Z-plasty after sustaining various types of injuries or finger pulp avulsion. A longitudinal incision was made along the lateral border of the digit and a large neurovascular volar flap was elevated just above the pulleys and flexor tendon sheath. To release tension, a large Z-plasty was applied at the metacarpophalangeal joint or interphalangeal joint crease. The final patient outcomes were reviewed retrospectively. RESULTS: All fingertip injuries were treated without flap necrosis. Partial wound dehiscence was observed in two patients and average static two-point discrimination was 5.2 mm. There were no postoperative contracture deformities, joint stiffness, paresthesia, or hypersensitivity. Most patients were left with acceptable scarring and were free of postoperative pain and cold intolerance during the long-term follow-up. CONCLUSIONS: Our novel technique provides durable, completely sensate, and well-vascularized coverage of the fingertip with minimal discomfort to patients.

Reconstruction of a temporal scalp defect without ipsilateral donor vessel possibilities using a local transposition flap and a latissimus dorsi free flap anastomosed to the contralateral side: a case report.

Scalp defects necessitate diverse approaches for successful reconstruction, taking into account factors such as defect size, surrounding tissue, and recipient vessel quality. This case report presents a challenging scenario involving a temporal scalp defect where ipsilateral recipient vessels were unavailable. The defect was effectively reconstructed utilizing a transposition flap and a latissimus dorsi free flap, which was anastomosed to the contralateral recipient vessels. Our report underscores the successful reconstruction of a scalp defect in the absence of ipsilateral recipient vessels, emphasizing the importance of employing appropriate surgical interventions without necessitating vessel grafts.

Multiple digit resurfacing with a lateral thoracic free flap: Two-stage mitten hand and division procedures.

PURPOSE: The conventional abdominal and groin flaps for resurfacing the defect have several disadvantages, including the risk of flap failure due to accidental traction or detachment, immobilization of the arm before division, and aesthetic dissatisfaction because of the flap bulkiness. The aim of this study was to share our experiences with the free lateral thoracic flap and elucidate the optimal timing of division in complex hand reconstruction, which yielded favorable outcomes in terms of both functionality and aesthetics. METHODS: This article is a retrospective review of multiple digit resurfacing using free tissue transfer from 2012 to 2022. Patients who underwent two-stage operation including mitten hand creation using superthin thoracodorsal artery perforator (TDAp) free flap and secondary division were included. A flap was elevated over the superficial fascia layer the midportion between the anterior border of the latissimus dorsi and pectoralis major muscles and once the pedicle was found, an outline that matched the defect was created. A process named "pushing with pressure and cutting" was carried out before pedicle ligation until all the superficial fat tissue had been removed except for around the perforator. Two cases (18%) involved defects of the entire fingers reconstructed by TDAp flap with anterolateral thigh flap. Six cases (55%) had a super-thin TDAp flap only. In two cases (18%), non-vascularized iliac bone grafting was required for finger lengthening. One case (9%) was resurfaced with a TDAp chimeric flap including a skin paddle with the serratus anterior muscle. The primary outcome was defined as the survival or failure of the flap, while the secondary outcomes associated complications such as infection and partial flap necrosis. A statistical analysis was not performed due to the size of the case series. RESULTS: All 13 flaps survived completely without any complications. Flap dimension ranged from 12 cm × 7 cm to 30 cm × 15 cm. Mitten hand duration prior to division was 41.9 days on average which was essential for the optimal result. During the division procedures, there were nine cases of debulking (82%), six cases of split-thickness skin graft (STSG) (55%), and three cases of Z-plasty performed on the first web space (27%). The mean follow-up period was 20.2 months. Mean Disability of the Arm, Shoulder, and Hand (DASH) Questionnaire score was 10.76. CONCLUSIONS: We resurfaced severe soft tissue defects of multiple fingers with thin to super-thin free flaps, mainly TDAp flaps. Surgeons can restore original hand shape using a two-stage reconstructive strategy of mitten hand creation and proper division timing to create a 3-dimensional hand structure, even in severely injured hands with multiple soft tissue defects of the digits.

Long-term results of huge deep-seated liposarcoma in the thigh: Two case reports.

RATIONALE: Liposarcoma is an uncommon malignant tumor that develops in the fatty tissue; thus, the long-term follow-up results of extremely large liposarcomas in the submuscular layer of the thigh have rarely been reported. Here we share the course and outcome of 2 cases of a huge deep-seated liposarcoma in the thigh. PATIENT CONCERNS: Two patients visited our clinic, each with a deep-seated mass in the thigh. First, a 44-year-old man presented to the outpatient clinic with a left thigh mass. Approximately 1 year later, an 80-year-old man presented to the outpatient clinic with a right posterior thigh mass. DIAGNOSIS: Magnetic resonance imaging revealed an approximately 14 × 8 × 21 cm well-differentiated liposarcoma between the sartorius and iliopsoas muscle and an approximately 14 × 12 × 31.5 cm lipomatous mass in the posterior compartment of the right thigh involving the right adductor muscles. After complete marginal resection, an excisional biopsy was performed to confirm the diagnosis. INTERVENTIONS: Both patients underwent complete marginal resection without chemotherapy or radiotherapy. OUTCOMES: A biopsy showed a 20 × 17 × 7 cm well-differentiated, well-encapsulated liposarcoma in the 44-year-old man and a 30 × 17 × 10 cm well-differentiated liposarcoma in the 80-year-old man. These patients have achieved approximately 61 and 44 months of recurrence-free survival to date, respectively. LESSONS: Here we described the long-term outcomes of 2 patients with a huge deep-seated liposarcoma in the lower extremity. Complete marginal excision of well-differentiated liposarcoma can achieve excellent recurrence-free survival.

Hydroethanolic Extract of Fritillariae thunbergii Bulbus Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Enhancing Intestinal Barrier Integrity.

The incidence of ulcerative colitis (UC), an inflammatory disorder of the gastrointestinal tract, has rapidly increased in Asian countries over several decades. To overcome the limitations of conventional drug therapies, including biologics for UC management, the development of herbal medicine-derived products has received continuous attention. In this study, we evaluated the beneficial effects of a hydroethanolic extract of Fritillariae thunbergii Bulbus (FTB) in a mouse model of DSS-induced UC. The DSS treatment successfully induced severe colonic inflammation and ulceration. However, the severity of colitis was reduced by the oral administration of FTB. Histopathological examination showed that FTB alleviated the infiltration of inflammatory cells (e.g., neutrophils and macrophages), damage to epithelial and goblet cells in the colonic mucosal layer, and fibrotic lesions. Additionally, FTB markedly reduced the gene expression of proinflammatory cytokines and extracellular matrix remodeling. Immunohistochemical analysis showed that FTB alleviated the decrease in occludin and zonula occludens-1 expression induced by DSS. In a Caco-2 monolayer system, FTB treatment improved intestinal barrier permeability in a dose-dependent manner and increased tight junction expression. Overall, FTB has potential as a therapeutic agent through the improvement of tissue damage and inflammation severity through the modulation of intestinal barrier integrity.

Network pharmacology-based identification of bioavailable anti-inflammatory agents from Psoralea corylifolia L. in an experimental colitis model.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional oriental medicine, the dried seeds of Psoralea corylifolia L. (PC) have been used to treat various diseases, including gastrointestinal, urinary, orthopedic, diarrheal, ulcer, and inflammatory disorders. AIM OF THE STUDY: Although its various biological properties are well-known, there is no information on the therapeutic effects and bioavailable components of PC against inflammatory bowel disease. Therefore, we focused on the relationship between hydroethanolic extract of PC (EPC) that ameliorates colitis in mice and bioactive constituents of EPC that suppress pro-inflammatory cytokines in macrophages. MATERIALS AND METHODS: We investigated the therapeutic effects of EPC in a dextran sulfate sodium-induced colitis mouse model and identified the orally absorbed components of EPC using UPLC-MS/MS analysis. In addition, we evaluated and validated the mechanism of action of the bioavailable constituents of EPC using network pharmacology analysis. The effects on nitric oxide (NO) and inflammatory cytokines were measured by Griess reagent and enzyme linked immunosorbent assay in lipopolysaccharide (LPS)-induced macrophages. RESULTS: In experimental colitis, EPC improved body weight loss, colon length shortening, and disease activity index. Moreover, EPC reduced the serum levels of pro-inflammatory cytokines and histopathological damage to the colon. Network pharmacological analysis identified 13 phytochemicals that were bioavailable following oral administration of EPC, as well as their potential anti-inflammatory effects. 11 identified EPC constituents markedly reduced the overproduction of NO, tumor necrosis factor-α, and/or interleukin-6 in macrophages induced by LPS. The LPS-induced expression of the nuclear factor kappa-light-chain-enhancer of activated B cells reporter gene was reduced by the 4 EPC constituents. CONCLUSIONS: The results indicate that the protective activity of EPC against colitis is a result of the additive effects of each constituent on the expression of inflammatory cytokines. Therefore, it suggests that 11 bioavailable phytochemicals of EPC could aid in the management of intestinal inflammation, and also provides useful insights into the clinical application of PC for the treatment of inflammatory bowel diseases.

Chemical Profile Determination and Quantitative Analysis of Components in Oryeong-san Using UHPLC-Q-Orbitrap-MS and UPLC-TQ-MS/MS.

In this study, a method to both qualitatively and quantitively analyze the components of Oryeong-san (ORS), which is composed of five herbal medicines (Alisma orientale Juzepzuk, Polyporus umbellatus Fries, Atractylodes japonica Koidzumi, Poria cocos Wolf, and Cinnamomum cassia Presl) and is prescribed in traditional Oriental medicine practices, was established for the first time. First, ORS components were profiled using ultra-high-performance liquid chromatography/quadrupole Orbitrap mass spectrometry, and 19 compounds were clearly identified via comparison against reference standard compounds. Subsequently, a quantitative method based on ultra-high-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry was established to simultaneously measure the identified compounds. Nineteen compounds were accurately quantified using the multiple-reaction-monitoring mode and used to analyze the sample; we confirmed that coumarin was the most abundant compound. The method was validated, achieving good linearity (R2 ≤ 0.9991), recovery (RSD, 0.11-3.15%), and precision (RSD, 0.35-9.44%). The results suggest that this method offers a strategy for accurately and effectively determining the components of ORS, and it can be used for quality assessment and management.

Strategy for resurfacing complex extremity defect with chimeric, linked flaps: A review with a 10-year experience at major trauma center.

For the reconstruction of the extensive and/or three-dimensional soft-tissue defect in upper and lower extremities, chimeric flaps composed of multiple flaps or tissues with separate vascular supplies can supply economical use of tissue and superior esthetic results. Herein, we investigated the effectiveness of the thoracodorsal axis chimeric flap through the review the largest collection of long-term data. A retrospective review of all patients who received the thoracodorsal axis chimeric flap in complex three-dimensional defects of extremities between January of 2012 and December of 2021. A total of 55 type I/IP classical chimeric flaps, 19 type II/IIP anastomotic chimeric flaps, five type III perforator chimeric flaps, and seven type IV mixed chimeric flaps were analyzed. As the reconstructed area became proximal, flap dimensions increased significantly. And the optimal flap type depended on the location. The TDAp flap can provide large dimensions of skin paddle with latissimus dorsi and serratus anterior muscles with acceptable donor-site morbidities. The TDAp chimeric flaps constructed by microvascular anastomosis of two free flaps can provide large skin dimensions but also tissues with different properties. These characteristics make it possible to resurface the large and extensive defects, reconstruct the complex distal extremity defects, needing tissues with different properties, and cover the three-dimensional defect, obliterating the dead space. The thoracodorsal axis chimeric flap could be a favorable option for extensive, complex, or three-dimensional defects of the upper and lower extremities based on its reliability of the vascular system.

Therapeutic effects of Pulsatilla koreana Nakai extract on ovalbumin-induced allergic rhinitis by inhibition of Th2 cell activation and differentiation via the IL-4/STAT6/GATA3 pathway.

Allergic rhinitis (AR), caused by immunoglobulin E (IgE)-mediated inflammation, generally occurs in the upper respiratory tract. T helper type 2 (Th2) cell-mediated cytokines, including interleukin (IL)-4, IL-5, and IL-13, are important factors in AR pathogenesis. Despite various treatment options, the difficulty in alleviating AR and pharmacological side effects necessitate development of new therapies. The root of Pulsatilla koreana Nakai (P. koreana), a pasque flower, has been used as a herbal medicine. However, its effects on AR remain unclear; therefore, we aimed to explore this subject in the current study. The therapeutic effects of P. koreana water extract (PKN) on the pathophysiological functions of the nasal mucosa was examined in ovalbumin (OVA)-induced AR mice. The effect of PKN on Th2 activation and differentiation was evaluated using concanavalin A-induced splenocytes and differentiated Th2 cells from naïve CD4+ T cells. We also investigated the effect of changes in JAK/STAT6/GATA3 signaling on IL-4-induced Th2 cells. In OVA-induced AR mice, PKN administration alleviated allergic nasal symptoms and decreased the total number of immune cells, lymphocytes, neutrophils, and eosinophils in nasal lavage fluid; serum levels of OVA-specific IgE, histamine, and IL-13 were also significantly reduced. PKN also ameliorated OVA-induced nasal mucosal tissue thickening by inhibiting inflammation and goblet cell hyperplasia. PKN treatment significantly inhibited Th2 activity and differentiation through the IL-4/STAT-6/GATA3 pathway in Th2 cells. PKN is an effective AR treatment with the potential to improve patients' daily lives by regulating the allergic inflammatory response induced by Th2 cells.

cAMP Activation of the cAMP Receptor Protein, a Model Bacterial Transcription Factor.

The active and inactive structures of the Escherichia coli cAMP receptor protein (CRP), a model bacterial transcription factor, are compared to generate a paradigm in the cAMP-induced activation of CRP. The resulting paradigm is shown to be consistent with numerous biochemical studies of CRP and CRP*, a group of CRP mutants displaying cAMP-free activity. The cAMP affinity of CRP is dictated by two factors: (i) the effectiveness of the cAMP pocket and (ii) the protein equilibrium of apo-CRP. How these two factors interplay in determining the cAMP affinity and cAMP specificity of CRP and CRP* mutants are discussed. Both the current understanding and knowledge gaps of CRP-DNA interactions are also described. This review ends with a list of several important CRP issues that need to be addressed in the future.

Gleditsia sinensis Lam. aqueous extract attenuates nasal inflammation in allergic rhinitis by inhibiting MUC5AC production through suppression of the STAT3/STAT6 pathway.

Allergic rhinitis (AR), a chronic respiratory inflammatory disease, is among the most common chronic diseases reported worldwide. Mucus hypersecretion is a critical feature of AR pathogenesis. Although the Gleditsia sinensis extract has several beneficial effects on human health, its effects on allergic inflammation have not yet been investigated. In this study, we examined the effects of G. sinensis aqueous extract (GSAE) on nasal inflammation in an ovalbumin (OVA)-induced AR mouse model. GSAE was administered orally for 1 week and then the clinical nasal symptoms were evaluated. The levels of histamine, OVA-specific immunoglobulin (Ig) E, and interleukin (IL)-13 were measured in the serum using an enzyme-linked immunosorbent assay (ELISA). Inflammatory cells were then counted in the nasal lavage fluid (NALF) and histopathology in the nasal epithelium was evaluated. STAT3/STAT6 phosphorylation was examined in primary human nasal epithelial cells (HNEpCs) using western blot analysis. Oral administration of GSAE to OVA-induced AR mice alleviated nasal clinical symptoms and reduced OVA-specific immunoglobulin E, interleukin (IL)-13, and histamine levels. The accumulation of eosinophils in nasal lavage fluid, nasal mucosa, mast cells, goblet cells, and mucin 5AC (MUC5AC) in the nasal epithelium was also inhibited by GSAE. Treatment with GSAE inhibited the production of MUC5AC in IL-4/IL-13-stimulated primary human nasal epithelial cells through the signal transducer and activator of transcription (STAT)3/STAT6 signaling pathway. These results indicated that GSAE reduces nasal inflammation suggesting that it is a potential treatment option for AR.

Isodorsmanin A Prevents Inflammatory Response in LPS-Stimulated Macrophages by Inhibiting the JNK and NF-κB Signaling Pathways.

Natural and synthetic chalcones exhibit anti-inflammatory, antitumoral, antibacterial, antifungal, antimalarial, and antitubercular activities. Isodorsmanin A (IDA), a chalcone, is a well-known constituent of the dried seeds of Psoralea corylifolia L. (PC). Although other constituents of PC have been widely investigated, there are no studies on the biological properties of IDA. In this study, we focused on the anti-inflammatory effects of IDA and evaluated its effects on lipopolysaccharide (LPS)-stimulated macrophages. The results showed that IDA suppressed the production of inflammatory mediators (nitric oxide [NO] and prostaglandin E2 [PGE2]) and proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and interleukin-1ß [IL-1ß]) without cytotoxicity. In addition, it downregulated the mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) within the treatment concentrations. In our mechanistic studies, IDA inhibited the phosphorylation of the c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK), and protected the nuclear factor of the kappa light polypeptide gene enhancer in the B-cells' inhibitor, alpha (IκB-α), from degradation, thus preventing the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells' (NF-κB) transcription factor. Our results suggest that IDA is a promising compound for attenuating excessive inflammatory responses.