Intense Pruritus Research Articles

A rare case report of diclofenac induced Steven Johnson syndrome

Stevens Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) are acute life-threatening mucocutaneous diseases characterized by extensive necrosis involving the mucous membrane and epidermis. In this case, a 54-year-old female after intake of prescribed diclofenac tablet presented with multiple reddish maculopapular eruptions over face, abdomen, both limbs, over lips and oral cavity associated with pain and intense pruritus. This case is a rare presentation of drug induced SJS caused by commonly prescribed NSAID, diclofenac. Patient’s condition improved after withdrawal of offending drug and prompt treatment. This case suggests that emphasis on early detection, assessment and timely management of adverse drug reactions is of upmost importance. Thus, establishment of proper vigilance centre and regular monitoring is necessary and taking caution in prescribing drugs as well in elderly groups.

Systemic Therapy for Atopic Dermatitis in Children and Adolescents: A United States Expert Consensus.

Atopic dermatitis (AD) is a chronic, type-2 mediated, inflammatory skin disease characterized by intense pruritus, disruption of skin barrier function, and immune dysregulation. Management strategies for AD are routinely determined based on disease severity. First-line treatment begins with basic skin care and topical anti-inflammatory medication, which is typically sufficient for the management of mild-to-moderate disease. For those patients with moderate-to-severe disease, systemic therapy is often required. This can involve off-label treatment with conventional immunosuppressant medications. However, this approach is limited by a lack of robust clinical trial data and safety concerns that necessitate close monitoring. The emergence of novel targeted biologics and small molecules to treat AD presents an opportunity to optimize AD management and patient outcomes by offering greater efficacy than traditional immunosuppressants and a favorable safety profile. As the treatment landscape shifts, clinicians can benefit from a standardized process of patient assessment and treatment, along with resources to help maintain contemporary knowledge of available therapeutic options. This United States (US)-based, expert-led consensus used a modified Delphi process to develop core recommendations for the use of systemic medications for the management of pediatric patients <18 years of age with moderate-to-severe AD.

EAR CANKER IN A RABBIT – A CASE REPORT

A three-month-old female New Zealand White Rabbit, weighing about 1.4 kg was brought to the Veterinary Clinical Complex, Veterinary College and Research Institute, Tirunelveli with ahistory of intense pruritis and alopecia all over the body. Clinical observation revealed crusty lesions on the nose,ear margin and toes. Microscopic examination of the deep skin scraping revealed the presence of Psoroptes cuniculi mite. The rabbit was treated with an injection Ivermectin @ 0.4 mg/kg sub-cutaneous and an injection of Chlorpheniramine maleate @ 0.4 mg/kg intramuscular and further advised the owner to give HITEK® oral solution (Ivermectin) @ 0.4 mg/kg PO once a week and Benzyl benzoate I.P. solution topically daily for a continuous period of one month along with multivitamin supplementation (Multistar pet®) @ 2 ml PO BID. The rabbit recovered successfully without any drug side effects (Tandem usage of ivermectin and Benzyl Benzoate).

Oral Administration of Taurodeoxycholate, A GPCR19 Agonist, Effectively Ameliorates Atopic Dermatitis in A Mouse Model.

Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disorder, characterised by intense pruritus and recurrent eczematous lesions. Recently, the US FDA has approved Janus kinase (JAK) inhibitors for oral treatment in AD patients. However, oral immunomodulatory agents have demonstrated adverse effects. In previous studies, we demonstrated the efficacy of topical taurodeoxycholate (TDCA), a G protein-coupled receptor 19 (GPCR19) agonist, on AD. In this study, we further evaluated the efficacy of orally administered TDCA on MC903- and dinitrochlorobenzene (DNCB)-induced AD mouse models. Oral administration of TDCA significantly ameliorated AD symptoms and reduced both epidermal and dermal thickness. Additionally, oral TDCA treatment inhibited the infiltration of myeloid and lymphoid cells into AD lesions. TDCA also suppressed the expression of thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-13, IL-33, IL-1β, tumour necrosis factor-alpha (TNF-α) and chemokine (C-C motif) ligand 17 in the skin and blood. Given the previously demonstrated safety profiles of TDCA, oral TDCA may offer a beneficial and safer alternative for AD patients.

Evaluation of Serum Calprotectin as an Alternative Diagnostic Marker for Intrahepatic Cholestasis of Pregnancy.

Background/Objectives: Intrahepatic cholestasis of pregnancy (ICP) is characterised by unexplained intense pruritus during pregnancy. While serum bile acid (BA) is the standard diagnostic marker for ICP, we explored the potential of serum calprotectin as an alternative diagnostic marker for ICP. Methods: Leftover serum specimens with known serum BA levels, collected from non-pregnant women and pregnant women with an ICP, were used to measure serum calprotectin levels using the Human calprotectin L1/S100-A8/A9 ELISA kit. Results: Serum calprotectin levels were measured in 79 pregnant women with ICP (median [interquartile range] 28 year; serum BA 20 [13.7-35.7] μMol/L; calprotectin159 pg/mL [122.2-212.3]); 43 pregnant women without ICP (age 28 years; serum BA 3.6 [2.1-5.8] μMol/L; calprotectin 146.5 pg/mL [75.8-194.8]), and 59 non-pregnant women (age 28 years; serum BA 3.5 [1.6-5.1 μMol/L; calprotectin 82.4 pg/mL [48.8-137.2]). Compared to non-pregnant women, calprotectin levels were significantly elevated among pregnant women with (p < 0.001) or without ICP (p = 0.01). Calprotectin levels were comparable between pregnant women with and without ICP (p = 0.15). The areas under the ROC curve, to differentiate the presence and absence of ICP, were 0.940 (0.903-0.977; p < 0.001) and 0.681 (0.604-0.759; p < 0.001) for BA and calprotectin, respectively. Conclusions: Serum calprotectin is raised in pregnant women regardless of the presence or absence of ICP and had an inferior diagnostic performance for ICP compared to BA. This information is crucial for understanding the challenges in ICP diagnosis and the limitations of serum calprotectin as an alternative marker.

Applied Research on Atopic Dermatitis with Special Emphasis on the Role of Emollients in This Disorder: A Review

Atopic dermatitis is a chronic and multifactorial inflammatory dermatosis. Recurrent eczematous lesions and intense pruritus very often reduce the quality of life of patients, affecting their mental health. For this reason, it is necessary to undertake treatment. Treatment should be characterized by an individual approach to the patient, taking into account the predominant pathogenetic factors in the development of atopic dermatitis and systematic skin care. Soothing the typical symptoms of AD, i.e., dry skin and persistent itching, involves emollients, which counteract xerosis and reduce the feeling of itching. Studies confirm that the regular use of emollients in patients with AD prolongs the period between relapses and alleviates the intensity of symptoms during periods of disease severity. This review paper aims to highlight the challenges that patients with atopic dermatitis face. This work will also present an indication of the rationale for the use of emollients in this condition, as well as an indication of the forms of their application in therapeutic and care preparations.

Integrative Treatment Approaches with Mind-Body Therapies in the Management of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex pathophysiology characterized by intense pruritus, often associated with psychological stress and atopic and non-atopic comorbidities that significantly reduce quality of life. The psychological aspects of AD and the interaction between the mind and body via the skin-brain axis have led to an interest in mind-body therapies (MBT). The aim of this article is, therefore, to reinforce the importance of psychodermatological care in AD. We performed a focused literature review on holistic practices or integrative MBT in AD, including education, cognitive behavioral therapy, habit reversal, meditation, mindfulness, hypnotherapy, eye movement desensitization and reprocessing, biofeedback, progressive muscle relaxation, autonomous sensory meridian response, music therapy, massage, and touch therapy. A multidisciplinary holistic approach with MBT, in addition to conventional pharmacologic antipruritic therapies, to break the itch-scratch cycle may improve AD outcomes and psychological well-being. Although there is a paucity of rigorously designed trials, evidence shows the potential benefits of an integrative approach on pruritus, pain, psychological stress, anxiety, depressive symptoms, and sleep quality. Relaxation and various behavioral interventions, such as habit reversal therapy for replacing harmful scratching with massaging with emollient 'plus', may reduce the urge to scratch, while education may improve adherence to conventional therapies.

Uncovering the Differences: How DLQI and WHO-5 Scores Vary in Moderate-to-Severe Psoriasis Patients Treated with Tildrakizumab 100 mg vs. 200 mg?

Background/Objectives: Psoriasis (PsO) is a chronic inflammatory skin disease that severely impacts patients' quality of life (QoL). Its global prevalence is about 2%, with significant regional variations. PsO manifests in the form of erythematous and scaly plaques, causing intense pruritus and discomfort and limiting daily activities. The condition often includes comorbidities such as psoriatic arthritis, cardiovascular diseases, and metabolic syndrome, further deteriorating QoL. Psychological well-being is notably affected, with high levels of depression and anxiety due to the visible lesions, leading to social stigma and isolation. QoL indexes like WHO-QoL and SF-36 assess various well-being aspects, while patient-reported outcomes (PROs) provide a comprehensive understanding of PsO's impact. However, there are no universally shared PROs in outpatient practice to fully understand the impact of the disease and associated therapies. This study aims to evaluate differences between DLQI and WHO-5 in adult patients with moderate-to-severe PsO treated with tildrakizumab 100 mg or 200 mg. Methods: The study was conducted at the University Hospital of Siena, Italy, from May 2023 to April 2024. Data from 15 patients treated with tildrakizumab 200 mg and 15 patients treated with tildrakizumab 100 mg, observed for at least 28 weeks, were recorded. Demographic data, PASI, DLQI, and WHO-5 scores were analyzed. Patients in the 100 mg group (G100) were selected to match the demographic characteristics of the 200 mg group (G200). Reduction rates of DLQI and WHO-5 were assessed at baseline values and after 4, 16, and 28 weeks. Results: Both groups experienced improvements in QoL. The group treated with 200 mg showed more pronounced and rapid reductions in DLQI and WHO-5 scores compared to the 100 mg group. WHO-5 demonstrated faster improvements in overall well-being than DLQI, indicating its greater sensitivity to changes in mental well-being and overall QoL. No differences in adverse events were observed between the two groups, with no major adverse events reported. Conclusions: In our study, WHO-5 proved more sensitive than DLQI in capturing well-being changes in PsO patients treated with tildrakizumab. However, a combined use of both WHO-5 and DLQI questionnaires should be encouraged in clinical practice. Furthermore, this study confirmed the superior QoL improvement associated with tildrakizumab 200 mg compared to 100 mg. Future research should explore the long-term impact on QoL and comparative effectiveness among other biologic therapies in diverse patient populations.

Extended Half-life Antibodies: A Narrative Review of a New Approach in the Management of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions, significantly impacting physical health and quality of life. The pathogenesis of AD involves genetic predisposition, immune dysregulation, and environmental factors, with a defective skin barrier playing a crucial role. Treatment options for AD include both topical and systemic therapies, with advanced treatments like Janus kinase inhibitors and biologics offering significant improvements but facing limitations in safety and dosing frequency. Extended half-life antibodies represent a promising advancement for the management of immune-mediated inflammatory diseases, including AD. These antibodies, engineered for prolonged circulation and reduced dosing frequency, target key cytokines and immune pathways known to be involved in the pathogenesis of AD, offering potential for less frequent administration while maintaining efficacy. Currently, two such agents are in phase2 trials. APG777, targeting interleukin-13 (IL-13), and IMG-007, targeting OX40 receptor, have shown promising preclinical and early clinical results. They demonstrated prolonged half-lives and the potential for less frequent dosage regimen, along with significant improvements in AD symptoms. These therapies could enhance patient adherence and reduce healthcare burdens by decreasing injection frequencies and clinic visits. As research continues, extended half-life antibodies could significantly improve AD management and patient quality of life. Further studies will determine the long-term safety and efficacy of extended half-life antibodies, with ongoing innovations in antibody engineering likely to broaden their applications and benefits.

Outcomes of kidney transplant recipients exposed to Chagas disease under Benznidazole prophylaxis. A single center 10-year experience.

Chagas disease (ChD) is endemic in many parts of the world and can be transmitted through organ transplantation or reactivated by immunosuppression. Organs from infected donors are occasionally used for transplantation, and the best way of managing the recipients remains a subject of debate. We present a single-center cohort study describing a 10-year experience of kidney transplantation in patients at risk of donor-derived ChD and or reactivation. Patients received prophylactic treatment with Benznidazole and were monitored for transmission or reactivation. Monitoring included assessing direct parasitemia, serology, and polymerase chain reaction (PCR). Fifty-seven kidney transplant recipients (KTRs) were enrolled in the study. Forty-four patients (77.2%) were at risk of primary ChD infection, nine patients (15.8%) were at risk of disease reactivation, and four patients (7.0%) were at risk of both. All patients received Benznidazole prophylaxis, starting on the first day after transplantation. Parasitemia was assessed in 51 patients (89.5%), serology also in 51 patients (89.5%), and PCR in 40 patients (70.2%). None of the patients exhibited clinically or laboratory-detectable signs of disease. A single patient experienced a significant side effect, a cutaneous rash with intense pruritus. At 1-year post-transplantation, the patient and graft survival rates were 96.5% and 93%, respectively. In this study, no donor-derived or reactivation of Trypanosoma cruzi infection occurred in KTRs receiving Benznidazole prophylaxis.

Rash decisions: A case report of Risperidone and exanthematous eruptions

Here, we describe a clinical case involving a 19-year-old male diagnosed with schizophrenia and initiated on risperidone 2 mg/day. The dose was gradually built up to 6 mg/day. Within a week, the patient manifested an extensive exanthematous eruption characterized by collarette-shaped desquamation and intense pruritus. The medication was promptly discontinued, and aripiprazole was introduced, resulting in the complete resolution of the cutaneous manifestations within the subsequent week.

Contact Dermatitis From Biomedical Devices, Implants, and Metals—Trouble From Within

Allergic contact dermatitis is characterized by its appearance of red, raised and infiltrated, scaling or scabbed skin and intense pruritus, and distinguished from irritant contact dermatitis by its specific immune process and histopathology. Many contact allergens are low molecular weight chemicals including metals such as nickel, cobalt, and chromium, preservatives, and adhesives. When such materials are used internally in biomedical devices, they are similarly capable of causing sensitization and an inflammatory response. Sometimes the reaction remains internal, and presents as swelling, pain, stiffness, decreased range of motion, and internal itching around the implant. Such reactions may, in some cases, also extend to include a localized or, rarely, systemic contact dermatitis indicative of the same process. This review will present an overview of reported skin and local internal reactions to orthopedic implants, which are the largest category of implanted internal metal devices. Immune reactions to smaller categories of medical appliances include cardiac devices and vascular stents, neuromodulation devices, diabetic appliances, Nuss bar surgery for pectus excavatum, and dental and spinal implants. We will review the available diagnostic tools, the consensus on interpretation, and reported strategies for treatment.

Eosinophils in hidradenitis suppurativa patients exhibit pro-inflammatory traits, implicating a potential pathogenic role in the disease.

Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful nodules, abscesses and purulent secretions in intertriginous regions. Intense pruritus frequently accompanies HS lesions, adding further discomfort for patients. While Th17 pathway activation is implicated in HS pathogenesis, disease mechanisms are still not fully understood, and therapeutics are lacking. Previous reports raise a potential role for eosinophils in HS, showing a strong association of eosinophil levels with disease severity. To investigate eosinophils in HS, we recruited patients and matched healthy controls and then performed flow-cytometry studies, eosinophil stimulation assays, and lesional skin staining for eosinophils. We found that HS patients reported similar levels of pain and itch. Compared to matched controls, HS blood exhibited decreased mature eosinophils and increased numbers of immature eosinophils, coupled with a significant increase in dermal eosinophilic infiltrates. Additionally, IL-17RA+ eosinophils were highly and significantly correlated with multiple HS-related clinical scores. In both stimulated and unstimulated conditions, HS eosinophils showed an inflammatory phenotype versus controls, including an increase in costimulatory T- and B-cell markers (e.g. CD5 and CD40) following all stimulations (TNFα/IL-17A/IL-17F). These findings highlight the significance of pruritus in HS and suggest a higher turnover of eosinophils in HS blood, potentially due to the consumption of eosinophils in skin lesions. Our data delineate the features and functions of eosinophils in HS and suggest that eosinophils participate in disease pathogenesis, advancing Th17-related inflammation. Further studies are needed to investigate eosinophils' response to current HS treatments and their potential as a therapeutic target in the disease.

Predicting Factors and Clinical Characteristics of Pruritus in Psoriasis: A Cross-Sectional Survey.

Pruritus is an important symptom among patients affected by psoriasis. To date, no general agreement has been established regarding pruritus as a measure of psoriasis severity. This study aims to assess psoriatic pruritis prevalence and characteristics using a comprehensive itch questionnaire. A semi-structured questionnaire consisting of 48 questions was applied to patients diagnosed with psoriasis and admitted to the Dermatology Department of Mures Clinical County Hospital, Romania. A total of 163 patients were enrolled, out of which 115 (70.55%) reported itch. Patients with itch had higher PASI (p = 0.003) and DLQI scores (p < 0.001). The itch was most frequently described as a crawling sensation, mainly located in the lesional skin and aggravated by stress and temperature variation. It had a moderate intensity (6.18 ± 2.46). Emollients were the treatment preferred by most patients in alleviating itch, while biologics exerted a protective effect on itch development (OR = -0.24; p < 0.0001) and negatively correlated with itch intensity (r = -0.23; p < 0.0001). Advanced age, high BMI, and PASI scores were indicators of itch presence, while female gender, high PASI score, and frequent itch episodes indicate highly intense pruritus (≥7 on the VAS). A better understanding of itch and its clinical features will guide physicians toward the best treatment option and would, ultimately, benefit the patient.

Periocular Manifestation in Acute Atopic Dermatitis in a Paediatric Patient. A Case Report

Atopic dermatitis is a chronic skin condition characterized by itchy, scaly, and crusted lesions, most commonly affecting infants and children. The condition presents with intense pruritus and a chronic course with exacerbations. Periorbital involvement is expected due to the thin and sensitive skin in this area, and the inflammation can be exacerbated by rubbing or scratching. This case reports a 5-year-old girl with bilateral periorbital inflammation that had been present for 4 hours. She had a history of atopic dermatitis and no known surgical history or medication allergies but was allergic to shellfish. No medication or topical cream was administered for the described episode. Upon waking up, she presented with newly developed periorbital inflammation. She had not consumed any food to which she was known to be allergic, and there had been no increase in eyelid scratching. There was no recollection of contact with any toxic agents. During the physical examination, erythematous scaly plaques were observed on both cheeks, chin, and neck, and periorbital inflammation accompanied by eyelid and periorbital Dennie-Morgan fold. The primary diagnosis was periorbital atopic dermatitis in the context of an acute atopic dermatitis flare-up. The prescribed treatment included prednisolone acetate (Estilsona) for five days and pimecrolimus for the atopic dermatitis. Atopic dermatitis is a complex condition with a multifactorial aetiology, and its management can be challenging. Further research is needed to develop more effective treatments for atopic dermatitis.

Innovative Topical Therapy for Otic Eczema

An innovative topical treatment for psoriasis and atopic dermatitis has recently received patent approval from the Spanish Ministry of Industry, Trade, and Tourism. This topical treatment Psorisbye, presented in the form of a lotion, includes a combination of clobetasol, papaverine hydrochloride, spironolactone, a milk-peptide complex, and propylene glycol. A 56-year-old female presented to our outpatient clinic with bilateral otic eczema. The patient had no significant past medical history and primarily complained of intense pruritus in the lesions. The patient was advised to use our recently patented lotion, Psorisbye, once daily for 7 days. Two days after beginning the treatment, the patient experienced significant relief from itching sensations. By the 8th day, during an examination at the outpatient clinic, a notable improvement in the scaled lesions was observed. While the preliminary results exhibited by Psorisbye in the context of this specific case are indeed promising, the imperative to establish its efficacy and reliability necessitates the initiation of further investigations characterized by more expansive sample sizes and prolonged follow-up periods.

Cutaneous inflammasome driving ASC / gasdermin-D activation and IL-1β-secreting macrophages in severe atopic dermatitis.

Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus, and chronic skin colonization by Staphylococcus aureus. To understand the inflammatory status in AD, we investigated the inflammasome complex, that activates ASC (Apoptosis-associated speck-like protein containing a CARD), caspase-1 and GSDMD (gasdermin-D), and production of IL-1β and IL-18. We aimed to evaluate the expression of the inflammasome pathway in the skin of adults with AD. Thirty patients with moderate to severe AD and 20 healthy controls were enrolled in the study. We performed the analysis of the inflammasome components NLRP1, NLRP3, AIM-2, IL-1β, IL-18, Caspase-1, ASC, GSDMD, and CD68 expression (macrophage marker) by immunohistochemistry and immunofluorescence. The main findings included increased expression of NLRP3, NLRP1 and AIM-2 at dermal level of severe AD; augmented IL-18 and IL-1β expression at epidermis of moderate and severe patients, and in the dermis of severe AD; augmented expression of ASC, caspase-1 and GSDMD in both epidermis and dermis of moderate and severe AD. We detected positive correlation between caspase-1, GSDMD and IL-1β (epidermis) and caspase-1 (dermis) and AD severity; NLRP3, AIM-2 and IL-1β, and NLRP3 with IL-18 in the epidermis; ASC, GSDMD and IL-1β, and NLRP3, AIM-2, caspase-1, and IL-18 in the dermis. We also evidenced the presence of CD68+ macrophages secreting GSDMD, ASC and IL-1β in moderate and severe AD. Cutaneous macrophages, early detected in moderate AD, have its role in the disease inflammatory mechanisms. Our study indicates a canonical activation pathway of inflammasomes, reinforced by the chronic status of inflammation in AD. The analysis of the inflammasome complex evidenced an imbalance in its regulation, with increased expression of the evaluated components, which is remarkably in severe AD, emphasizing its relevance as potential disease biomarkers and targets for immunomodulatory interventions.

Ayurvedic Management of Vulvovaginal Candidiasis with Local Application of Guduchi-Triphala-Danti Gel

Vulvovaginal candidiasis is the infection of the vaginal mucosa and/or vulva caused by the Candida species, a gram-positive yeast-like fungus. It is the second most common vulvovaginal infection characterized by thick-curdy white-cottage-cheese type vaginal discharge and intense vulvovaginal pruritus. Symptomatically vulvovaginal candidiasis can be compared with Slaishmiki yonivyapat in Ayurveda, the line of management of which is the use of Ruksha and Ushna aushadha. Local application of gel has the advantages of easy administration, more bioavailability of drugs, and prolonged retention without much local irritation. The classical Guduchi-Triphala-Danti pariseka yoga, mentioned in Yonivyapat chikitsa has been modified into a gel form, facilitating self-administration by women. Methodology: Here is a case report of a 31-year-old multiparous woman who presented with complaints of curdy white vaginal discharge associated with itching over the vulvar region for the last 6 months. She was diagnosed with vulvovaginal candidiasis by vaginal swab culture. Intervention with Guduchi-Triphala-Danti gel was carried out for 14 days for 2 consecutive cycles excluding days of menstruation and followed up after the next 30 days without medication. Results: After completion of the treatment protocol there was substantial relief of symptoms like curdy white vaginal discharge and itching over the vulvar region, wet-mount microscopy was negative for pseudohyphae, and the vaginal swab culture showed no growth. Conclusion: Local application of Guduchi-Triphala-Danti gel was found to be effective in the management of vulvovaginal candidiasis.

Study on the Mechanism of Anti-atopic Dermatitis by Herba Siegesbeckiae Based on System Pharmacology

Background: Atopic dermatitis (AD) is a common but complex chronic inflammatory skin condition characterised by intense pruritus, severely impacting patients’ quality of life. At present, there is no specific drug for AD. Herba Siegesbeckiae (HS) had a therapeutic effect on AD, but its mechanism has not been completely elucidated. Purpose: We aimed to understand the mechanism of HS in the treatment of AD in this study. Materials and methods: To investigate the mechanism of HS for AD, including active components, key targets and pathway analyses, systemic pharmacology was used. Molecular docking was conducted to validate the interactions between the key components and their targets. Afterwards, an AD-like animal model was established, skin pathology was observed and immunohistochemical staining was used to confirm the key targets. Results: Six vital active components (daucosterol, d-mannitol, hythiemoside B, 15,16-di- O-acetyldarutoside, 19-acetoxy-15-hydroperoxy-12-oxo-13,14E-dehydro-10,11,14,15-tetrahydr-ogeranylnerol and 17- O-acetyldarutoside) highly correlated with potential targets and the key targets (TNF-α, VEGFA, TLR4, STAT3, TLR2, STAT1, MMP9, IL-6, TRPV1 and PPARG) highly correlated with disease processes were identified, pathway enrichment analysis revealed that the toll-like receptor, PI3K-Akt and HIF-1 signalling pathways were significantly enriched with key targets, suggesting their involvement in the anti-Alzheimer’s disease mechanism of HS. As a result of animal experiments, AD-like mice from the model group showed epidermal thickening and inflammatory cell infiltration; TNF-α, VEGFA, TLR4, STAT3, TLR2, STAT1, MMP9, IL-6, TRPV1 levels are significantly up-regulated and PPARG levels were significantly down-regulated; those of which could be reversed by 3.0 g/kg. Conclusion: HS might exert its anti-AD effects by up-regulating PPARG and down-regulating TNF-α, VEGFA, TLR4, STAT3, TLR2, STAT1, MMP9, IL-6 and TRPV1. This study laid a foundation for understanding HS’s bioactive components and mechanism against AD.

Navigating Perinatal Challenges: A Comprehensive Review of Cholestasis of Pregnancy and Its Impact on Maternal and Fetal Health.

Cholestasis of pregnancy (CP), or intrahepatic CP (ICP), represents a condition peculiar to pregnancy, marked by impaired bile acid flow and consequent accumulation in the maternal bloodstream. Primarily emerging in the third trimester, CP is linked with considerable risks to both the mother and fetus, including heightened incidences of preterm birth, fetal distress, and stillbirth, alongside maternal complications such as intense pruritus and liver dysfunction. Despite its clinical significance, the etiology of CP, which involves genetic, hormonal, and environmental factors, remains partially understood. This comprehensive review delves into the physiology and pathophysiology of CP, outlines its clinical manifestations and diagnostic criteria, and discusses the associated maternal and fetal complications. Furthermore, it evaluates current management strategies, prognostic implications, and potential long-term effects on maternal and child health. It also explores future research directions, emphasizing the need for advancements in understanding the pathophysiology of CP, developing novel therapeutic interventions, and improving risk stratification models. By offering a thorough overview of CP, this review aims to enhance clinical awareness, guide management practices, and identify areas requiring further investigation, ultimately contributing to better health outcomes for affected women and their babies.