Studying the Effect of Sertraline in Reducing Aggressive Behavior in Patients with Major Depression

Purpose: Depression causes dysfunction in various spheres of individual and social life, which is now considered as the fourth-leading cause of the global disease burden. Given that violence and aggression associated with depression in the community cause serious damage to the family, the prediction, early detection and effective treatment of aggressive and violent behavior are essential. The present study compared the severity of aggression before and after treatment with sertraline in patients with major depression. Methods: This is an intervention type study and the study population consisted of patients with depression and aggression. The sampling included 23 eligible patients. Data were obtained by SCID-I, SCID-II, STAXI-II, BDI-II and was also analyzed using SPSS 23 software. Results: The results showed that depression, anger mood, desire to verbally express anger, controlling anger and anger control before treatment was reduced but the desire for physical expression of anger increased. Conclusion: Obtained results in this research support the effect of Sertraline on reduction of severity of depression, reduction of severity of symptoms of aggression and anger (state of anger, anger feeling, and the tendency to express anger verbally), increased controlling external anger and significantly controlling internal anger. Hence, Sertraline can be found effective in the treatment of patients with depression and aggressive behaviors. Also Sertraline increases tend to cause physical representation of anger, then this issue supports the increase in the euthanasia behavior in primary days of treatment with SSRI that requires more assessments

Evaluation of PEGylated fibrin as a three-dimensional biodegradable scaffold for ovarian tissue engineering

The most challenging task of creating a bioengineered ovary to restore fertility in cancer patients is choosing an appropriate biomaterial to encapsulate isolated preantral follicles and ovarian cells. In this study, as a biocompatible and biodegradable biomaterial containing fibrin-like bioactivity and manageable physical properties, PEGylated fibrin aims to encapsulate isolated ovarian stromal cells as a first step of creating an engineered ovarian tissue. For this purpose, human ovarian stromal cells were isolated from frozen-thawed ovarian tissue and cultured in the PEGylated fibrin hydrogels (PEG:Fib), which were fabricated by combining two different molar ratios of PEG:Fib (10:1 and 5:1) and two thrombin concentrations. The samples were analyzed at days 0 and 5 of in vitro for cell density, proliferation (Ki67), and apoptosis (caspase-3). Moreover, LIVE/DEAD and PrestoBlue assays assessed cell viability and proliferation on days 1, 3, and 5. The effect of PEGylation on the biodegradation behavior of fibrin was evaluated by measuring the remaining mass ratio of non-modified fibrin, PEG:Fib 10:1, and PEG:Fib 5:1 hydrogels after 1, 2, 3, 5, 8, 11, and 15 days. The results showed that PEGylated fibrin hydrogels enhanced scaffold stability and supported cell viability and proliferation. In addition, PEG:Fib 5:1 T50 indicated a significantly higher cell density dynamic and non-significantly lower expression of caspase-3 on day 5. Besides, uniformity of cell distribution inside the hydrogel and a tendency to a high rate of Ki67-positive cells was observed in PEG:Fib 10:1 T50 hydrogels. In conclusion, this study reveals the positive effects of PEGylated fibrin hydrogels on isolated human ovarian stromal cells. Based on such promising findings, we believe that this matrix should be tested to encapsulate isolated human ovarian follicles

Nanoemulsion applications in photodynamic therapy

Nanoemulsion, or nanoscaled-size emulsions, is a thermodynamically stable system formed by blending two immiscible liquids, blended with an emulsifying agent to produce a single phase. Nanoemulsion science has advanced rapidly in recent years, and it has opened up new opportunities in a variety of fields, including pharmaceuticals, biotechnology, food, and cosmetics. Nanoemulsion has been recognized as a potential drug delivery technology for various drugs, such as photosensitizing agents (PS). In photodynamic therapy (PDT), PSs produce cytotoxic reactive oxygen species under specific light irradiation, which oxidize the surrounding tissues. Over the past decades, the idea of PS-loaded nanoemulsions has received researchers' attention due to their ability to overcome several limitations of common PSs, such as limited permeability, non-specific phototoxicity, hydrophobicity, low bioavailability, and self-aggregation tendency. This review aims to provide fundamental knowledge of nanoemulsion formulations and the principles of PDT. It also discusses nanoemulsion-based PDT strategies and examines nanoemulsion advantages for PDT, highlighting future possibilities for nanoemulsion use

A review on biomaterials for ovarian tissue engineering.

Considerable challenges in engineering the female reproductive tissue are the follicle's unique architecture, the need to recapitulate the extracellular matrix, and tissue vascularization. Over the years, various strategies have been developed for preserving fertility in women diagnosed with cancer, such as embryo, oocyte, or ovarian tissue cryopreservation. While autotransplantation of cryopreserved ovarian tissue is a viable choice to restore fertility in prepubertal girls and women who need to begin chemo- or radiotherapy soon after the cancer diagnosis, it is not suitable for all patients due to the risk of having malignant cells present in the ovarian fragments in some types of cancer. Advances in tissue engineering such as 3D printing and ovary-on-a-chip technologies have the potential to be a translational strategy for precisely recapitulating normal tissue in terms of physical structure, vascularization, and molecular and cellular spatial distribution. This review first introduces the ovarian tissue structure, describes suitable properties of biomaterials for ovarian tissue engineering, and highlights recent advances in tissue engineering for developing an artificial ovary. STATEMENT OF SIGNIFICANCE: The increase of survival rates in young cancer patients has been accompanied by a rise in infertility/sterility in cancer survivors caused by the gonadotoxic effect of some chemotherapy regimens or radiotherapy. Such side-effect has a negative impact on these patients' quality of life as one of their main concerns is generating biologically related children. To aid female cancer patients, several research groups have been resorting to tissue engineering strategies to develop an artificial ovary. In this review, we discuss the numerous biomaterials cited in the literature that have been tested to encapsulate and in vitro culture or transplant isolated preantral follicles from human and different animal models. We also summarize the recent advances in tissue engineering that can potentially be optimal strategies for developing an artificial ovary

Study of hybrid alginate/gelatin hydrogel-incorporated niosomal Aloe vera capable of sustained release of Aloe vera as potential skin wound dressing

Nowadays, wound dressings serve as advanced skin products, which mainly aim to accelerate the wound healing process. The wound dressings with a potential of localized and prolonged release of therapeutic agents have attracted tremendous attention. In this study, synthesis of a sustained release of niosomal Aloe vera (AV) loaded in alginate/gelatin (AG) hybrid hydrogel is aimed at improving skin regeneration as wound dressing. For this purpose, AV-loaded niosomes are synthesized and incorporated in the hybrid AG hydrogel. The size and polydispersity index (PdI) of niosomes, AV entrapment efficacy and AV in vitro release are characterized. In addition, the hydrogel characteristic, such as swelling ratio, degradation behavior and mechanical property, are studied. MTT assay is utilized to evaluate the effect of AV incorporation and release on the proliferation of fibroblast cells. Results demonstrate that size, PdI and EE% of AV-loaded niosomes are 270.080 nm, 0.108 and 42.039 ± 4.090%, respectively, and in vitro release of AV is about 20% after 7 days. AG hybrid hydrogel loaded by niosomal AV shows an extended sustained release manner, where its swelling ratio and percentage of degradation are 60 wt% after 72 h and 70 wt% after 6 days, respectively. The average Young’s modulus of the hybrid hydrogel is measured around 12.64 ± 1.3 kPa, which seems suitable as a wound dressing. Finally, MTT assay confesses an increased fibroblast proliferation in the presence of AV, particularly in the niosomal AV-loaded hydrogel. Concludingly, alginate/gelation hybrid hydrogel incorporated with niosomal AV, with sustained release potential can be suggested as a promising candidate for wound dressing applications

Secure transplantation by tissue purging using photodynamic therapy to eradicate malignant cells.

The field of photodynamic therapy (PDT) for treating various malignant neoplasms has been given researchers' attention due to its ability to be a selective and minimally invasive cancer therapy strategy. The possibility of tumor cell infection and hence high recurrence rates in cancer patients tends to restrict autologous transplantation. So, the photodynamic tissue purging process, which consists of selective photoinactivation of the malignant cells in the graft, is defined as a compromising strategy to purify contaminated tissues before transplantation. In this strategy, the direct malignant cells' death results from the reactive oxygen species (ROS) generation through the activation of a photosensitizer (PS) by light exposure in the presence of oxygen. Since new PS generations can effectively penetrate the tissue, PDT could be an ideal ex vivo tissue purging protocol that eradicates cancer cells derived from various malignancies. The challenge is that the applied pharmacologic ex vivo tissue purging should efficiently induce tumor cells with minor influence on normal tissue cells. This review aims to provide an overview of the current status of the most effective PDT strategies and PS development concerning their potential application in ex vivo purging before hematopoietic stem cell or ovarian tissue transplantation

Photodynamic cancer therapy using liposomes as an advanced vesicular photosensitizer delivery system.

The multidisciplinary field of photodynamic therapy (PDT) is a combination of photochemistry and photophysics sciences, which has shown tremendous potential for cancer therapy application. PDT employs a photosensitizing agent (PS) and light to form cytotoxic reactive oxygen species and subsequently oxidize light-exposed tissue. Despite numerous advantages of PDT and enormous progress in this field, common PSs are still far from ideal treatment because of their poor permeability, non-specific phototoxicity, side effects, hydrophobicity, weak bioavailability, and tendency to self-aggregation. To circumvent these limitations, PS can be encapsulated in liposomes, an advanced drug delivery system that has demonstrated the ability to enhance drug permeability into biological membranes and loading both hydrophobic and lipophilic agents. Moreover, liposomes can also be coated by targeting agents to improve delivery efficiency. The present review aims to summarize the principles of PDT, various PS generations, PS-loaded nanoparticles, liposomes, and their impact on PDT, then discuss recent photodynamic cancer therapy strategies using liposomes as PS-loaded vectors, and highlight future possibilities and perspectives

Mind the mechanical strength: tailoring a 3D matrix to encapsulate isolated human preantral follicles.

Would a hydrogel with similar mechanical properties to the human ovarian cortex support preantral follicle development? Yes, our tailored PEGylated fibrin hydrogel was shown to significantly improve follicle growth One of the main challenges in developing an engineered ovary is to provide a 3D matrix that supports the follicle architecture and the interaction between granulosa cells and the oocyte as they are essential for folliculogenesis. Thanks to its biocompatibility and bioactivity, fibrin has been employed to fabricate a 3D matrix to encapsulate ovarian follicles. However, follicles lose their physical support within a few days owing to rapid fibrin degradation. Therefore, different strategies, including physical and chemical modifications, have been developed to enhance the stability of fibrin. By developing a matrix made of a synthetic (polyethylene glycol: PEG) and natural polymer (fibrin), we aimed to overcome fibrin degradation by the chemical reaction of PEGylation and tailor a PEGylated fibrin hydrogel formulation with mechanical strength similar to the ovarian cortex in women of reproductive age. To this end, response surface methodology was employed to obtain a tailored formulation of PEGylated fibrin. This hydrogel was then tested to encapsulate and support isolated human preantral follicles A PEGylated fibrin formulation was tailored using mathematical modeling software to mimic the mechanical properties of human ovarian tissue at reproductive age. Human preantral follicles were isolated from 11 patients of reproductive age and encapsulated in the tailored hydrogels, which were cultured for 4 or 7 days. Follicle survival and diameter were assessed on Days 1 and 7. Furthermore, the follicles were subjected to confocal microscopy to evaluate their growth (Ki67 staining) on Day 7 and analyze cell-cell communication (connexin 43 and transzonal projection staining) on Day 4. In this study, mathematical modeling was applied to achieve the biomechanically tailored PEGylated fibrin formulation by targeting the specific goal of 3178 ± 245 Pascal, Young's modulus of ovarian cortical tissue in reproductive-age women. Our results demonstrated that the PEGylated fibrin hydrogel consisting of 39.06 mg/ml of PEGylated fibrinogen and 50.36 IU/ml of thrombin was the optimum condition with the desirability of 97.5%. This tailored hydrogel yielded a high follicle survival rate (83%) after 7 days of culture and supported its development up to the secondary stage. Follicle growth was confirmed by the presence of Ki67-positive granulosa cells on Day 7. Additionally, connexin 43 and Phalloidin staining indicated the retention of connections between granulosa cells and the oocyte. N/A. In this study, our tailored hydrogel was only tested , which is not the same as the physiological environment. It is crucial to conduct a study assessing the follicles following their encapsulation in the tailored hydrogel and transplantation, which will be the next step of our investigation. The findings from this study introduced a suitable biomaterial similar to the ovarian cortex in reproductive-age women in terms of biomechanical properties for encapsulating human preantral follicles. This biomaterial allowed the radial growth of follicles and preserved their viability. Furthermore, PEGylation improved the stability of fibrin and the physical support of follicles. This study was supported by grants from the Fondation Louvain (PhD scholarship awarded to S.M., as part of a legacy from Mr Frans Heyes, and PhD scholarship awarded to A.D. as part of a legacy from Mrs Ilse Schirmer). The authors declare no competing interests