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Clinical, Cosmetic and Investigational... 2024This study seeks to investigate the effect of evodiamine on psoriasis and psoriatic pruritus.
PURPOSE
This study seeks to investigate the effect of evodiamine on psoriasis and psoriatic pruritus.
METHODS
Imiquimod-induced psoriasiform dermatitis in mice was used as a model, and evodiamine was topically applied for seven days. The mice were observed daily for skin damage on the back, clinical score and their scratching behavior was recorded. Blood samples were collected on the final day of the experiment, and the serum levels of pruritus-associated inflammatory cytokines tumor necrosis factor (TNF) -α, interleukin (IL) -23, and IL-17A were measured using enzyme-linked immunosorbent assay. Histopathological changes were observed in Hematoxylin and Eosin-stained skin specimens. The expression levels of transient receptor potential vanilloid (TRPV) 1, TRPV3, TRPV4, and the pruritus-related mediators Substance P (SP), nerve growth factor (NGF), and calcitonin gene-related peptide (CGRP) in the skin lesions were analyzed using Western blot and qRT-PCR. The effect of evodiamine on the exploratory behavior, motor, and coordination abilities of mice was assessed using open field, suspension, and Rota-Rod experiments. Molecular docking was utilized to verify the binding of evodiamine to the residues of TRPV1, TRPV3, and TRPV4.
RESULTS
Evodiamine reduced pruritus and inhibited inflammation by decreasing the levels of inflammatory mediators TNF-α, IL-23, and IL-17A in the serum of Imiquimod-induced mice and attenuated the mRNA and protein expression levels of SP, NGF, CGRP, TRPV1, TRPV3, and TRPV4 in the skin.
CONCLUSION
Evodiamine is an effective treatment for psoriasis and pruritus, due to its ability to inhibit immune inflammation and pruritic mediators.
PubMed: 38948922
DOI: 10.2147/CCID.S462446 -
Cancer Innovation Feb 2024In recent years, the three-dimensional (3D) culture system has emerged as a promising preclinical model for tumor research owing to its ability to replicate the tissue... (Review)
Review
In recent years, the three-dimensional (3D) culture system has emerged as a promising preclinical model for tumor research owing to its ability to replicate the tissue structure and molecular characteristics of solid tumors in vivo. This system offers several advantages, including high throughput, efficiency, and retention of tumor heterogeneity. Traditional Matrigel-submerged organoid cultures primarily support the long-term proliferation of epithelial cells. One solution for the exploration of the tumor microenvironment is a reconstitution approach involving the introduction of exogenous cell types, either in dual, triple or even multiple combinations. Another solution is a holistic approach including patient-derived tumor fragments, air-liquid interface, suspension 3D culture, and microfluidic tumor-on-chip models. Organoid co-culture models have also gained popularity for studying the tumor microenvironment, evaluating tumor immunotherapy, identifying predictive biomarkers, screening for effective drugs, and modeling infections. By leveraging these 3D culture systems, it is hoped to advance the clinical application of therapeutic approaches and improve patient outcomes.
PubMed: 38948532
DOI: 10.1002/cai2.101 -
Frontiers in Surgery 2024Pelvic organs prolapse remains a significant health concern affecting millions of women worldwide. The use of native tissues to suspend the apex has acquired relevance...
INTRODUCTION
Pelvic organs prolapse remains a significant health concern affecting millions of women worldwide. The use of native tissues to suspend the apex has acquired relevance in urogynecologic surgery. One of the most commonly used procedures performed without mesh is the technique described by Shull, consisting of suturing the vaginal apex to the uterosacral ligaments. The objective of the study is to evaluate the learning curve of laparoscopic Shull's repair for the correction of pelvic floor defects, including the surgery time and surgical outcomes.
MATERIALS AND METHODS
This is a retrospective study conducted at the Policlinico G. Martino, University of Messina, Messina, Italy, and Policlinico Vanvitelli, Vanvitelli University, Naples, Italy. All patients affected by grade I-IV POP, consisting of apical prolapse with or without cystocele, and who underwent laparoscopic Shull's technique for prolapse correction were enrolled. The endpoints to estimate the learning curve for the procedure were the percentage of laparoscopic procedures completed, operative time, and the early complication rate.
RESULTS
A total of 31 laparoscopic Shull repairs were collected for the study. To evaluate the learning curve of the technique, we divided the 31 cases into three different groups: Procedures 0-10; 11-20; 21-31. The parameter for evaluating technique learning was the operative time. Group 21-31 demonstrated an operative time of 97 min (SD 20), compared with 121 min (SD 23) in group 0-10 and 120 min (SD 13) in group 11-20. A comparison of these means through ANOVA showed a -value of 0.01 for the entire system, and 0.95 for the comparison between 0 and 10 and 11-20, 0.04 for 0-10 vs. 21-31, and 0.02 between 11 and 20 and 21-31.
CONCLUSIONS
The rate of surgical improvement in terms of time became effective after an average of 20 procedures. However, the improvement seems to be effective case by case for surgeons skilled in basic endoscopy.
PubMed: 38948480
DOI: 10.3389/fsurg.2024.1396438 -
Regenerative Therapy Jun 2024With the increasing emphasis on the use of nonanimal ingredients in clinical care, studies have proposed the use of TrypLE™ as an alternative to trypsin. However,...
INTRODUCTION
With the increasing emphasis on the use of nonanimal ingredients in clinical care, studies have proposed the use of TrypLE™ as an alternative to trypsin. However, previous research has reported insufficient cell yield and viability when using TrypLE to isolate skin cells compared to the dispase/trypsin-EDTA method. This study aimed to propose an improved method for increasing the yield and viability of cells isolated by TrypLE and to evaluate isolated keratinocytes and melanocytes.
METHODS
Foreskin tissues were isolated to keratinocytes and melanocytes using the trypsin-EDTA protocol and our modified TrypLE protocol. The yield and viability of freshly isolated cells were compared, the epidermal residue after cell suspension filtration was analyzed histologically, and the expression of cytokeratin 14 (CK14) and Melan-A was detected by flow cytometry. After cultivation, keratinocytes and melanocytes were further examined for marker expression and proliferation. A coculture model of melanocytes and HaCaT cells was used to evaluate melanin transfer.
RESULTS
The yield, viability of total cells and expression of the keratinocyte marker CK14 were similar for freshly isolated cells from both protocols. No differences were observed in the histologic analysis of epidermal residues. Moreover, no differences in keratinocyte marker expression or melanocyte melanin transfer function were observed after culture. However, melanocytes generated using the TrypLE protocol exhibited increased Melan-A expression and proliferation in culture.
CONCLUSION
Our TrypLE protocol not only solved the problems of insufficient cell yield and viability in previous studies but also preserved normal cell morphology and function, which enables the clinical treatment of depigmentation diseases.
PubMed: 38948130
DOI: 10.1016/j.reth.2024.05.014 -
ACS Omega Jun 2024This study conducts a systematic investigation of the creation and optimization of a rutin-loaded transethosome intended for topical use. The formulation's...
This study conducts a systematic investigation of the creation and optimization of a rutin-loaded transethosome intended for topical use. The formulation's characteristics were thoroughly assessed for vesicle size (160.45 ± 1.98 nm), polydispersity index (0.235 ± 0.067), and zeta potential (-22.89 mV), with an entrapment efficiency and drug loading of 89.99 ± 1.55% and 8.9 ± 2.11%, respectively, and found to have a spherical shape by the use of transmission electron microscopy. The conversion to a gel suitable for application on the skin was carried out. The drug release form Opt-RUT-TE formulation (73.61 ± 2.55%) was significantly higher than that of release form RUT-suspension (34.52 ± 1.19%). The drug that permeated the skin from Opt-RUT-TEG (935.25 ± 10.49 μg/cm) was significantly higher than the permeability from RUT-Suspension gel (522.57 ± 6.79 μg/cm). Notably, tape stripping analysis revealed that the Opt-RUT-TE gel effectively penetrated the skin layers, with a higher concentration observed in the epidermis-dermis than in the RUT-suspension gel. The transethosomal gel exhibited favorable characteristics, highlighting its capacity to efficiently permeate the skin and suppress the growth of microorganisms, and Opt-RUT-TEG showed a higher microorganism inhibition zone (Gram-positive bacteria) than that of RUT-suspension gel. The investigation highlights the significant therapeutic possibilities of rutin in a transethosomal gel formulation for treating dermatological diseases by improving skin permeability and exhibiting antibacterial effects.
PubMed: 38947795
DOI: 10.1021/acsomega.4c01718 -
Neuropsychiatric Disease and Treatment 2024Absence seizures are classically associated with behavioral arrest and transient deficits in consciousness, yet substantial variability exists in the severity of the... (Review)
Review
Absence seizures are classically associated with behavioral arrest and transient deficits in consciousness, yet substantial variability exists in the severity of the impairment. Despite several decades of research on the topic, the pathophysiology of absence seizures and the mechanisms underlying behavioral impairment remain unclear. Several rationales have been proposed including widespread cortical deactivation, reduced perception of external stimuli, and transient suspension of the default mode network, among others. This review aims to summarize the current knowledge on the neural correlates of impaired consciousness in absence seizures. We review evidence from studies using animal models of absence epilepsy, electroencephalography, functional magnetic resonance imaging, magnetoencephalography, positron emission tomography, and single photon emission computed tomography.
PubMed: 38947367
DOI: 10.2147/NDT.S391052 -
Research Square Jun 2024Organoid cultures offer a powerful technology to investigate many different aspects of development, physiology, and pathology of diverse tissues. Unlike standard tissue...
Organoid cultures offer a powerful technology to investigate many different aspects of development, physiology, and pathology of diverse tissues. Unlike standard tissue culture of primary breast epithelial cells, breast organoids preserve the epithelial lineages and architecture of the normal tissue. However, existing organoid culture methods are tedious, difficult to scale, and do not robustly retain estrogen receptor (ER) expression and responsiveness in long-term culture. Here, we describe a modified culture method to generate and maintain organoids as suspension cultures in reconstituted basement membrane (™Matrigel). This method improves organoid growth and uniformity compared to the conventional Matrigel dome embedding method, while maintaining the fidelity of the three major epithelial lineages. Using this adopted method, we are able to culture and passage purified hormone sensing (HS) cells that retain ER responsiveness upon estrogen stimulation in long-term culture. This culture system presents a valuable platform to study the events involved in initiation and evolution of ER-positive breast cancer.
PubMed: 38947074
DOI: 10.21203/rs.3.rs-4463390/v1 -
Food Research International (Ottawa,... Aug 2024Fungal contaminations of cereal grains are a profound food-safety and food-security concern worldwide, threatening consumers' and animals' health and causing enormous...
Fungal contaminations of cereal grains are a profound food-safety and food-security concern worldwide, threatening consumers' and animals' health and causing enormous economic burdens. Because far-ultraviolet C (far-UVC) light at 222 nm has recently been shown to be human-safe, we investigated its efficacy as an alternative to thermal, chemical, and conventional 254 nm UVC anti-fungal treatments. Our microplasma-based far-UVC lamp system achieved a 5.21-log reduction in the conidia of Aspergillus flavus suspended in buffer with a dose of 1032.0 mJ/cm, and a 5.11-log reduction of Fusarium graminearum conidia in suspension with a dose of 619.2 mJ/cm. We further observed that far-UVC treatments could induce fungal-cell apoptosis, alter mitochondrial membrane potential, lead to the accumulation of intracellular reactive oxygen species, cause lipid peroxidation, and result in cell-membrane damage. The lamp system also exhibited a potent ability to inhibit the mycelial growth of both A. flavus and F. graminearum. On potato dextrose agar plates, such growth was completely inhibited after doses of 576.0 mJ/cm and 460.8 mJ/cm, respectively. To test our approach's efficacy at decontaminating actual cereal grains, we designed a cubical 3D treatment chamber fitted with six lamps. At a dose of 780.0 mJ/cm on each side, the chamber achieved a 1.88-log reduction of A. flavus on dried yellow corn kernels and a 1.11-log reduction of F. graminearum on wheat grains, without significant moisture loss to either cereal type (p > 0.05). The treatment did not cause significant changes in the propensity of wheat grains to germinate in the week following treatment (p > 0.05). However, it increased the germination propensity of corn kernels by more than 71% in the same timeframe (p < 0.05). Collectively, our results demonstrate that 222 nm far-UVC radiation can effectively inactivate fungal growth in liquid, on solid surfaces, and on cereal grains. If scalable, its emergence as a safe, cost-effective alternative tool for reducing fungi-related post-harvest cereal losses could have important positive implications for the fight against world hunger and food insecurity.
Topics: Fusarium; Aspergillus flavus; Edible Grain; Ultraviolet Rays; Spores, Fungal; Food Contamination; Food Irradiation; Food Microbiology; Reactive Oxygen Species
PubMed: 38945594
DOI: 10.1016/j.foodres.2024.114550 -
International Journal of Surgery Case... Jun 2024A right side diaphragmatic injury was linked to serious trauma to the abdomen, pelvis, and chest. The most significant type of injury was blunt abdominal trauma...
INTRODUCTION
A right side diaphragmatic injury was linked to serious trauma to the abdomen, pelvis, and chest. The most significant type of injury was blunt abdominal trauma sustained in a car collision. The left side was more likely than the right to experience herniation. The stomach and colon were the most often herniated abdominal viscera. In the same location as the diaphragm rupture, there were rib fractures, hemothorax, and liver damage. Delayed diaphragmatic rupture with diaphragmatic hernia is rare and has a mysterious nature.
CASE PRESENTATION
A 68 years old female patient who has repeated history of shortness of breath, for which she treated as lung infection presented with sudden exacerbation of shortness of breath, she witnessed history of blunt trauma 20 years back and up on investigation bowel herniation to the chest cavity diagnosed. Posteriolateral thoracotomy done, the herniated bowel reduced and the diaphragmatic defect repaired. The patient significantly improved and discharged from the hospital smoothly on 4th postoperative day.
DISCUSSION
Careful recording of past history and physical examination are the best approaches in diagnosing delayed presentation of traumatic diaphragmatic rupture. CT scan with reconstruction of the diaphragm is helpful in both diagnosis and differential diagnosis. Surgical therapy after diagnosis is the best treatment.
CONCLUSION
Delayed right side diaphragmatic hernia is a rare entity resulting in grave consequences, In a patient with history of trauma there should be a high index of suspension and patients should undergo imaging and surgical management is the best treatment.
PubMed: 38943935
DOI: 10.1016/j.ijscr.2024.109973 -
Regulatory Toxicology and Pharmacology... Jun 2024Depressive disorders are one of the most common mental disorders globally and progress in treating these disorders has been hampered, in part, by a lack of suitable... (Review)
Review
Depressive disorders are one of the most common mental disorders globally and progress in treating these disorders has been hampered, in part, by a lack of suitable nonclinical efficacy tests. Two common tests used in nonclinical efficacy studies of antidepressants-the forced swim test (FST) and tail suspension test (TST)-have come under criticism in recent years for their inconsistency and lack of validity, yet they continue to be used in the pharmaceutical industry. In this review, we provide a rationale for why international pharmaceutical regulatory and guidance agencies should begin issuing direction on methods for non-clinical efficacy testing that traditionally use the FST and TST, particularly considering that some regulators, such as those in the U.S. and E.U., allow the authorization of clinical trials to proceed without requiring tests in animals. The area of antidepressant drug discovery represents an important opportunity for reducing the attrition of psychiatric drugs, harmonizing regulatory requirements, and reducing animal use. Specific recommendations for the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) have been provided.
PubMed: 38942190
DOI: 10.1016/j.yrtph.2024.105666