Application of biomacromolecule-based passive penetration enhancement technique in superficial tumor therapy: A review.

Transdermal drug delivery (TDD) has shown great promise in superficial tumor therapy due to its noninvasive and avoidance of the first-pass effect. Especially, passive penetration enhancement technique (PPET) provides the technical basis for TDD by temporarily altering the skin surface structure without requiring external energy. Biomacromolecules and their derived nanocarriers offer a wide range of options for PPET development, with outstanding biocompatibility and biodegradability. Furthermore, the abundant functional groups on biomacromolecule surfaces can be modified to yield functional materials capable of targeting specific sites and responding to stimuli. This enables precise drug delivery to the tumor site and controlled drug release, with the potential to replace traditional drug delivery methods and make PPET-related personalized medicine a reality. This review focuses on the mechanism of biomacromolecules and nanocarriers with skin, and the impact of nanocarriers' surface properties of nanocarriers on PPET efficiency. The applications of biomacromolecule-based PPET in superficial tumor therapy are also summarized. In addition, the advantages and limitations are discussed, and their future trends are projected based on the existing work of biomacromolecule-based PPET.

Decellularization and characterization of camel pericardium as a new scaffold for tissue engineering and regenerative medicine.

BACKGROUND: Valvular heart diseases (VHDs) have become prevalent in populations due to aging. Application of different biomaterials for cardiac valve regeneration and repair holds a great promise for treatment of VHD. Aortic valve replacement using tissue-engineered xenografts is a considered approach, and the pericardium of different species such as porcine and bovine has been studied over the last few years. It has been suggested that the animal origin can affect the outcomes of replacement. METHODS: So, herein, we at first decellularized and characterized the camel pericardium (dCP), then characterized dCP with H&E staining, in vitro and in vivo biocompatibility and mechanical tests and compared it with decellularized bovine pericardium (dBP), to describe the potency of dCP as a new xenograft and bio scaffold. RESULTS: The histological assays indicated less decluttering and extracellular matrix damage in dCP after decellularization compared to the dBP also dCP had higher Young Modulus (105.11), and yield stress (1.57 ± 0.45). We observed more blood vessels and also less inflammatory cells in the dCP sections after implantation. CONCLUSIONS: In conclusion, the results of this study showed that the dCP has good capabilities not only for use in VHD treatment but also for other applications in tissue engineering and regenerative medicine.

Efficacy of baricitinib in the treatment of Systemic lupus erythematosus (SLE): A Systemic review and meta-analysis.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. It affects multiple organ systems and is associated with significant morbidity and mortality. The treatment for SLE primarily aims at controlling and remitting the disease. Baricitinib is a kinase inhibitor that selectively inhibits JAK1 and JAK2 enzymes. Recently this drug is being investigated as a potential therapeutic option for SLE. Objective: To analyze the efficacy of baricitinib in treating SLE. Methods: Search of databases identified relevant studies that reported the efficacy of baricitinib. Data of patient characteristics, intervention details, and outcomes was extracted. The data from the studies were pooled using a random-effects model. The odds ratio with their respective 95 % confidence intervals (CI) were calculated to analyze the results. A p value of <0.05 was considered statistically significant. Results: 3 RCTs were included in the analysis. 1849 patients were extracted from the included studies, most of the participants were females with a mean age of 43 years. The studies showed a significant effect of Baricitinib 4 mg in achieving SRI-4 [OR = 1.42 (95 % CI: 1.01, 2.00); p = 0.04]. There was no significant association of Baricitinib 2 mg in achieving SRI-4. Both dosages of the drug did not have any significant association in achieving LLDAS as compared to placebo. Serious adverse side effects were significantly associated with Bar 4 mg as compared to Bar 2 mg. Conclusion: Our meta-analysis suggests that baricitinib might be a potential treatment option for SLE. Further large-scale clinical trials are needed to confirm our findings. Potential side effects should also be considered while the administration of this drug.

Long-term outcome of treatments for Graves disease in the children and adolescent population.

BACKGROUND: Several studies were conducted over the years to find a significant association between non-surgical therapies such as Antithyroid Drug (ATD) Therapy and Radio-iodo therapy (RIT) with Graves' disease (GD) remission and relapse. However, these investigations did not have a specific focus on the age category of children and adolescents. Hence, this Research is performed to assess the association of non-surgical therapy (ATD and RIT) with Graves' disease (GD) remission and relapse in the children and adolescent population. DESIGN: A systematic review and meta-analysis of observational studies and clinical trials were carried out. METHODS: A systematic search of PubMed, EMBASE, and SCOPUS from their inception till April 2022 was performed for studies stating an association between ATD therapy and GD remission and relapse in participants 1-17 years old. The random-effects model was used in the meta-analysis to provide a pooled proportion of both primary outcomes. The quality and each study were assessed using the Newcastle Ottawa Scale (NOS). RESULT: From 6195 studies searched from the databases, only 16 relevant articles remained after a detailed evaluation. These studies, having a total of 2557 patients aged 5-17 years, were involved in the analysis with a pooled estimate showing a significant association of ATD therapy with GD remission (Estimate: 0.400, 95% Confidence interval: 0.265-0.535; I^2 = 98.16%) and with GD relapse (Estimate: 0.359, 95% Confidence interval: 0.257-0.461; I^2 = 98.26%). Subgroup analyses were conducted to assess the remission rate of different therapies suggesting that antithyroid drugs play a significant role in the remission of the patients. All included studies were classified as moderate quality. CONCLUSION: Following meta-analysis suggested that the ATD used in the analysis is effective in remitting GD in the children and adolescents population. Nevertheless, long-term RIT therapy and thyroidectomy leads to hypothyroidism. Still, large-sample, and high-quality studies targeting ATDs' use in children and adolescents with long-term surveillance of prognosis are needed.

Leader instigated task conflict and its effects on employee job crafting; the mediating role of employee attributions.

The role of leaders in conflict management remains the favorite area of researchers. This study aims to introduce a unique role of leaders in conflict named as leader instigated task conflict. We proposed that leader instigated task conflict promotes job crafting behaviors of employees by considering attributions regarding leader instigated conflict as mechanism for this relationship. Data were collected from 247 employees working in teams in marketing departments of different organizations across Pakistan. Data analyses was conducted through multilevel structural equation modeling. Findings revealed that leader instigated task conflict is positively related to promotion-focused job crafting and negatively related to prevention-focused job crafting via the mediating role of constructive conflict instigation attribution and destructive conflict instigation attribution respectively. The current study contributes to the literature on conflict by suggesting that leaders can be a source of task based conflict to achieve its positive outcomes. However, employee attributions play a vital role in achieving the positive outcomes of leader instigated task conflict, hence leaders must be careful about shaping constructive attributions of followers regarding their conflict instigation behavior in order to promote constructive behavioral responses of employees.

Assembly of multifunction dyes and heat shock protein 90 inhibitor coupled to bovine serum albumin in nanoparticles for multimodal photodynamic/photothermal/chemo-therapy.

The proangiogenic protein, survivin, is a client protein for heat shock protein 90 (Hsp-90), whose overexpression is induced by photodynamic therapy (PDT), leading to the inhibition of capase-9 and the blockage of apoptosis. The overexpression of Hsp-90 in cancer cells can rapidly acquire thermoresistance during photothermal therapy (PTT), leading to insufficient apoptosis, increased cell viability, and tumor recurrence. A potential approach to block the PTT-induced overexpression of Hsp-90 and the overexpression of survivin is developed by using an Hsp-90 inhibitor and anticancer agent, namely, geldanamycin (GM). These inhibitors also develop a mild-temperature PTT strategy to reach synergistic PDT and PTT efficiency. Thus, Cy7-SQ is designed by a covalent disulfide linkage between a photothermal agent (i.e., canine dye 7 [Cy7]) and a photosensitizer (i.e., squaraine dye [SQ]) for the improved photostability and thermal stability of Cy7 and SQ. The cleavage of the Cy7-SQ linkage by glutathione in a tumor microenvironment increases the efficiency of synergistic PDT and PTT. In the current study, bovine serum albumin (BSA)/Cy7-SQ/GM nanoparticles are developed through the self-assembly of BSA, Cy7-SQ, and GM to accelerate the apoptosis of cancer cells via near-infrared (NIR) laser irradiation, thus realizing Hsp-90-regulated synergistic PDT/PTT combined with chemotherapy.

The topical application of tranexamic acid to control bleeding in inguinal hernia surgery candidate patients: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Inguinal hernia surgery is a common procedure, especially for the elderly, who usually use anticoagulants and antiplatelet drugs. In this study, we evaluated the effectiveness of tranexamic acid (TXA) on the complications of inguinal hernia repair in patients using antiplatelets. PATIENTS AND METHODS: This study is a randomized controlled trial that was performed during the 2018-2019 years. Forty patients with inguinal hernia and antiplatelet use were enrolled randomly into the two groups. In the intervention group, the patients received two injectable form (500mg/5 mL) of TXA, totally 10 mL as a topical application at the surgical site, and then the patient's surgical site was seen every 8 h for 48 h, and the patient was examined daily for one week. RESULTS: The mean length of hospitalization, seroma, hematoma and infection in the two groups were not statistically significant (P > 0.05). However, the duration of surgery in the TXA group was significantly shorter than in the control group (54.85 vs. 68.72 min) (P < 0.001). The mean bleeding during surgery was significantly lower in the TXA group than in the control group (P < 0.001). CONCLUSION: The findings of present study indicate that topical TXA has a high ability to control bleeding. As a result, TXA is beneficial in terms of reducing bleeding and increasing the surgeon's satisfaction. Therefore, it is recommended that TXA be prescribed for patients requiring inguinal hernia surgery with a high risk of bleeding.

Employee voice behavior as a critical factor for organizational sustainability in the telecommunications industry.

Organizational effectiveness is contingent upon employees' contributions; however, the role of employee voice behavior as a critical component of employees' contribution to the organization has not been sufficiently acknowledged. Based on proactive behavior theory, we present a model to investigate employee voice behavior as an underlying mechanism in the relationship between supervisor delegation and perceived workplace inclusion. Using the SEM (structural equation modeling) method, we test our model's hypotheses with data from 271 employee-supervisor questionnaires administered in state-owned enterprises in the telecommunications industry. The results show that supervisor delegation is positively related to employees' promotive and prohibitive voice behavior. Promotive voice significantly influences perceived workplace inclusion, but prohibitive voice behavior was not found to have any impact on perceived workplace inclusion. Moreover, both dimensions of voice behavior, i.e., promotive and prohibitive voice behavior, significantly mediate the relationship between supervisor delegation and perceived workplace inclusion.

Comparing the in vivo and in vitro effects of hypoxia (3% O2) on directly derived cells from murine cardiac explants versus murine cardiosphere derived cells.

Coronary heart disease (CHD) is still one of the main causes of death in the world, despite significant advances in clinical treatments. Stem cell transplantation methods have the potential to improve cardiac function and patients' outcome following heart attack, but optimal cell types, cell preparation methods and cell delivery routes are yet to be developed. Mammalian hearts contain a small fraction of progenitor cells which, in culture, migrate out of the cardiac explants, known as explant-derived cell (EDCs) and contribute to spheroids known as cardiospheres (Csphs). Following further culture and cell passaging, Csphs give rise to cardiosphere-derived cells (CDCs). EDCs, Csphs and CDCs show in vitro and in vivo angiogenesis and tissue regeneration in myocardial ischemia. However, CDC and Csph formation is time consuming, expensive and not always successful. Therefore, this study aims to compare EDCs with CDCs and assess the effect of hypoxic preconditioning on their pro-angiogenic potential. The data showed that preconditioning EDCs in hypoxic cell culture enhances cell growth, viability and expression of stem cell and pro-angiogenic markers more than CDCs. In vivo experiments using a sub-dermal matrigel plug assay showed that EDCs and CDCs alone have limited pro-angiogenic potential; however, hypoxic preconditioning of EDCs and CDCs significantly enhances this process. Further research will increase our understanding of cardiac stem cell mediated angiogenesis and improve clinical therapies for myocardial infarction (MI) patients.