Elucidating the Role of Pro-renin Receptors in Pancreatic Ductal Adenocarcinoma Progression: A Novel Therapeutic Target in Cancer Therapy.

Pancreatic cancer is a highly aggressive malignancy with a very poor prognosis. The 5- year survival in these patients is very low, and most patients develop drug resistance to current therapies, so additional studies are needed to identify the potential role of new drug targets for the treatment of pancreatic cancer. Recent investigations have been performed regarding the roles of pro-renin receptors (PRR) in the initiation and development of cancers. PRR is a component of the local renin-angiotensin system (RAS). Local tissue RAS has been known in diverse organ systems, including the pancreas. Various investigations have implicated that PRRs are associated with the upregulation of various signaling pathways, like the renin-angiotensin system pathway, PI3K/Akt/mTOR, and the Wnt-signaling pathways, to contribute to pathological conditions, including cancer. In this review, we presented an overview of the role of PRR in the progression of pancreatic adenocarcinoma.

Evaluation of systemic oxidative stress in patients with melasma.

BACKGROUND: The significance of oxidative stress has been assessed and proven in the etiopathogenesis of many cutaneous disorders, but there are few studies that evaluated the role of only some factors involved in oxidative stress in patients with melasma. OBJECTIVE: This study aimed to examine the role of oxidative stress in melasma and assess the relationship between systemic oxidative stress and the severity and extension of this disease. METHODS: In this study, the serum levels of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), malondialdehyde (MDA), protein carbonyl (PC), selenium (Se), vitamin E (vit E), and vitamin C (vit C) of fifty patients with melasma were compared with those of fifty controls. RESULTS: The serum level of MDA was significantly higher in the melasma group (3.08 vs. 2.35 U/mL; p < 0.05), and it was positively correlated with the severity (r = 0.4; p < 0.001) and extension (r = 0.3; p < 0.05) of the disease. Furthermore, the serum level of vit C was significantly lower in melasma patients (2.16 vs. 2.57 µg/mL; p < 0.001). CONCLUSION: Systemic oxidative stress has a key role in the etiopathogenesis of melasma. Serum concentrations of MDA and vitamin C are indicators of this impairment.

Targeting Lysyl Oxidase as a Potential Therapeutic Approach to Reducing Fibrotic Scars Post-operatively: Its Biological Role in Post-Surgical Scar Development.

Abdominal and pelvic surgery, or any surgical injury of the peritoneum, often leads to chronic abdominal adhesions that may lead to bowel obstruction, infertility, and pain. Current therapeutic strategies are usually ineffective, and the pathological mechanisms of the disease are unclear. Excess collagen cross-linking is a key mediator for extra-cellular matrix deposition and fibrogenesis. Lysyl oxidase is a key enzyme that catalyzes the formation of stabilizing cross-links in collagen. Dysregulation of Lysyl oxidase (Lox) expressing upregulates collagen cross-linking, leading ECM deposition. Tissue hypoxia during surgery induces molecular mechanisms and active transcription factors to promote the expression of several genes related to inflammation, oxidative stress, and fibrosis, such as transforming growth factor beta, and Lox. Studies have shown that targeting Lox improves clinical outcomes and fibrotic parameters in liver, lung, and myocardial fibrosis, therefore, Lox may be a potential drug target in the prevention of postsurgical adhesion.

Review the Role of Metabolism Reprogramming in the Pathogenesis of Post-surgical Adhesion: A New Therapeutic Strategy.

Metabolic reprogramming is defined as the skill of cells to change their metabolism to support the induced energy demand due to continuous growth. Metabolic reprogramming is a well- known occurrence in the progression of neoplastic cells, although, evidence has shown that it is present in fibrotic disorders. Post-surgical adhesion as a fibrotic disorder is a medical challenge and is defined by fibrotic bands connected between organs with the abdominal wall. Despite many investigations carried out about the pathogenesis of the disorder but there are many unknowns, therefore, targeting special pathways may have the potential to prevent the formation of fibrotic bands post-operative. Glycolysis is a necessary metabolic pathway in living cells. In hypoxic conditions, it is the dominant pathway in the production of energy for different types of cells such as fibroblasts, immune cells, and endothelial cells. Also, glycolysis is a main downstream target for transforming growth factor ß (TGF-ß) and upregulates during fibrotic conditions. Furthermore, this is noteworthy that hypoxia induces factor 1 alpha (HIF-1α) as a transcription factor, elevated during the hypoxia condition stimulates different signaling pathways such as TGF-ß/SMAD, nuclear factor kappa B (NF-kB), and mTOR pathway to control glycolytic metabolism and T-cell trafficking for immune cell migration. Different evidence has indicated that the administration of glycolytic inhibitors has the potential to prevent the development of fibrotic markers. In this review, we pointed out the role of the glycolysis pathway and its connection to profibrotic cytokines to promote inflammatory and fibrotic pathways. Based on the results of studies related to fibrotic disorders we hypothesized that targeting glycolysis may have therapeutic potential in the prevention of postoperative adhesions.

Targeted delivery of doxorubicin and therapeutic FOXM1 aptamer to tumor cells using gold nanoparticles modified with AS1411 and ATP aptamers.

Objectives: A targeted delivery platform was prepared to co-deliver both doxorubicin (Dox) as an anticancer drug and FOXM1 aptamer as a therapeutic substance to breast cancer cells (4T1 and MCF-7) to reduce Dox side effects and increase its therapeutic efficacy. The targeted system (AuNPs-AFPA) consisted of FOXM1 aptamer, AS1411 aptamer (targeting oligonucleotide), ATP aptamer, and gold nanoparticles (AuNPs) as a carrier. Materials and Methods: AuNPs were synthesized by reduction of HAuCl4. Next, after pegylation of ATP aptamer, FOXM1 aptamer-PEGylated ATP aptamer conjugate (FPA) was prepared. Then, the AS1411 aptamer and FPA were exposed to the AuNPs surface through their thiol groups. Subsequently, Dox was loaded into the complex to form a targeted therapeutic complex. Results: The data of the MTT assay displayed that the targeted complex could remarkably reduce cell viability rate in target cells due to the overexpression of nucleolin on their cell membranes compared to nontarget cells, showing the targeting ability of AuNPs-AFPA-Dox. The in vivo antitumor effect confirmed that AuNPs-AFPA-Dox was capable of remarkably diminishing tumor growth relative to the free Dox in mice bearing 4T1 tumor cells. Conclusion: The results confirmed that the targeted system improved the therapeutic effect by loading high amounts of Dox alongside the presence of the therapeutic effect of FOXM1 aptamer. Finally, it can be concluded that AuNPs-AFPA-Dox by enhancing antitumor effectiveness and reducing toxicity toward non-target cells, can be used potentially as an effective strategy for the treatment of breast cancer.

Bilirubin as a new antioxidant in melasma.

BACKGROUND: Oxidative stress and its role in the pathogenesis of cutaneous diseases have been widely investigated. However, there are few studies that have solely assessed the contribution of intracellular antioxidants in the etiopathology of melasma. Furthermore, there are convincing reports about antioxidant properties of bilirubin (Bil) and uric acid (UA) in some skin disorders but not melasma. OBJECTIVE: This study aimed to determine serum levels of two major extracellular antioxidants (Bil and UA) levels in patients with melasma and their correlation with the severity and extent of the disease. METHODS: In this case-control study, the serum levels of bilirubin and uric acid of 50 melasma patients were compared with 50 healthy controls. Moreover, the correlation of serum concentrations of these antioxidants with the extent and severity of the disease were assessed. RESULTS: The serum concentration of Bil was significantly higher in the case group (p < 0.05). Furthermore, serum Bil level had a positive correlation with the extent of the melasma (correlation coefficient, +0.3; p < 0.05). No significant difference was found between the serum concentrations of UA between the study and control group. Neither Bil nor UA had a significant correlation with the severity of the disease. CONCLUSION: Oxidative stress may play a major role in the etiopathology of melasma and bilirubin, as an antioxidant, could be involved in the process of oxidative stress.

A highly sensitive fluorescent aptasensor for detection of prostate specific antigen based on the integration of a DNA structure and CRISPR-Cas12a.

Herein, a facile fluorescent CRISPR-Cas12a-based sensing strategy is presented for prostate specific antigen (PSA), as a prostate cancer biomarker, with the assistance of a cruciform DNA nanostructure and PicoGreen (PG) as a fluorochrome. Highly sensitive recognition of PSA is one of the virtues of the proposed method which comes from the use of unique features of both CRISPR-Cas12a and DNA structure in the design of the aptasensor. The presence of PSA creates a cruciform DNA nanostructure in the sample which can be loaded by PG and make sharp fluorescence emission. While, when there is no PSA, the CRISPR-Cas12a digests sequences 1 and 3 as single-stranded DNAs, causing no DNA structure and a negligible fluorescence is detected after addition of PG. This aptasensor presents a sensitive recognition performance with detection limit of 4 pg/mL and a practical use for determination of PSA in serum samples. So, this analytical strategy introduces a convenient and highly sensitive approach for detection of disease biomarkers.

Which laboratory/ultrasonographic parameters affect the severity of hirsutism?

BACKGROUND AND OBJECTIVES: Hirsutism is associated with other androgen-dependent signs/symptoms. This study was designed with the aim of a comprehensive investigation of laboratory and ultrasonographic findings in hirsute women and their probable association with the "severity" of the disease. PATIENTS AND METHODS: This cross-sectional study included 123 hirsute women. Comprehensive medical history of each patient was recorded, and a broad physical examination was performed by a single dermatologist. Ferriman-Gallwey score was used to evaluate the hirsutism severity. Pelvic ultrasonography was done by a single radiologist for each patient, and serum levels of the follicular stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, prolactin, thyroid-stimulating hormone, total testosterone, dehydroepiandrosterone sulfate, 17-alpha-hydroxyprogesterone, and cortisol were measured. The association of hirsutism severity and these paraclinical parameters was investigated. RESULTS: A statistically significant association was observed between polycystic ovary disease (PCOD) and the severity of hirsutism. A past medical history of PCOD was found to cause more severe forms of hirsutism in the involved patients as well. The presence of hormonal abnormalities was also significantly associated with the severity of hirsutism. CONCLUSIONS: More than half of the hirsute patients have endocrine abnormalities and/or PCOD. These two disorders are associated with the severity of hirsutism.

Photodynamic therapy of vitiligo: A pilot study.

BACKGROUND: Vitiligo is an acquired autoimmune skin disorder with depigmented macules and patches. There are several possible treatments for vitiligo, none of which could be considered as a definitive cure. Photodynamic therapy (PDT) is a novel treatment with controversial outcomes in vitiligo patients. MATERIALS & METHODS: A total of 10 patches (5 patches on the trunk, 3 on the extremities, and 2 on the neck) were selected and received microderm abrasion. Then the lesion was covered with 5- aminolevulinic acid (ALA) for one hour. Afterwards, it received red light with a dose of 120 J/cm2.This cycle was repeated monthly for 5 sessions. Another vitiligo patch was considered as a control and received topical mometasone twice a day during the study. The therapeutic results were compared by a blind dermatologist. RESULTS: The median of repigmentation score, which was determined by a blind dermatologist, was 0.5 in the PDT group and 1 in the steroid group, which did not show any statistically significant difference. CONCLUSION: The results of this study demonstrated that PDT does not have any additional therapeutic effect in comparison with topical corticosteroids as the traditional treatment of vitiligo.

Clinical Diagnosis has a High Negative Predictive Value in Evaluation of Malignant Skin Lesions.

BACKGROUND: The increasing incidence of skin cancers in fair-skinned population and its relatively good response to treatment make its accurate diagnosis of great importance. We evaluated the accuracy of clinical diagnosis of malignant skin lesions by comparing the clinical diagnosis with histological diagnosis as the gold standard. MATERIALS AND METHODS: In this retrospective study, we assessed all the pathology reports from specimens sent to a university hospital laboratory in 3 consecutive years from March 2008 to March 2010. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios were calculated for clinical diagnosis of malignant skin lesions stratified by their histological subtype. RESULTS: A total 4,123 specimen were evaluated. The sensitivity and specificity for clinical diagnosis of malignancy were 90.48% and 82.85%, respectively, whereas the negative predictive value was shown to be 99.06%. The positive and negative likelihood ratios were 5.23 and 0.11, respectively. CONCLUSION: Pathological assessment of skin lesions remains the cornerstone of skin cancer diagnosis. The high NPV and the relatively low PPV indicate that clinical diagnosis is more efficient in ruling out malignancies rather than diagnosing them.

Mucocutaneous Manifestations in HIV-Infected Patients and Their Relationship to CD4 Lymphocyte Counts.

BACKGROUND: More than 90% of human immunodeficiency virus- (HIV-) infected patients show at least one mucocutaneous manifestation during the course of their disease. The frequency, pattern, and associated factors of these complications vary among different populations. OBJECTIVE: This study was planned to evaluate the frequency of cutaneous presentations in HIV-infected patients and their association with the count of CD4 cells. METHODS: A cross-sectional study was conducted on eighty-four HIV-positive patients, who attended the Behavior Consultation Center of Arak University of Medical Sciences. All subjects had a complete physical examination by an expert dermatologist. Further diagnostic procedures were performed, if necessary. Counts of CD4 were determined using flow cytometry. RESULTS: From 84 patients who enrolled in this study, 95.2% manifested at least one type of mucocutaneous lesions. The most common presentation was xerosis, followed by seborrheic dermatitis, herpes simplex, and oral candidiasis. Oral candidiasis and furuncle were significantly associated with decrease in CD4 cell counts. CONCLUSIONS: Cutaneous manifestations are common in HIV-positive patients, some of which (oral candidiasis and furuncle) could be applicable as useful clinical indicators to predict the immune status of the patients. Therefore, regular skin examinations are recommended as routine HIV-infected patients' healthcare programs.

A Comprehensive Review of Cutaneous Manifestations Associated with COVID-19.

The novel coronavirus (SARS-CoV-2), the cause of coronavirus 2019 disease (COVID-19) pandemic, is associated with some cutaneous manifestations. Although the cutaneous presentations of COVID-19 are infrequent, it is of great importance for all clinicians to be aware of these manifestations, as it may contribute to sooner and better diagnosis and management of the disease, even in asymptomatic or paucisymptomatic patients. The reported cutaneous manifestations of COVID-19 are various, dispersed, and sometimes confusing. In this article, all reported cases to date were collected and classified under 6 major groups: maculopapular rash, urticaria, chilblain, vesicular lesions, livedo reticularis, and petechiae. Different characteristics of each group were discussed in detail as well.

Boosting landfill gas production from lignin-containing wastes via termite hindgut microorganism.

Lignocellulose comprises a significant portion of municipal solid waste (MSW) - 40-70% in developed countries, including paper, wood, and yard waste. Cellulose and hemicellulose are often shielded by lignin, posing a barrier to waste decomposition and landfill gas generation. Unfortunately, lignin is resistant to microbial degradation under low-oxygen conditions that normally occur in MSW landfills. The bacterium strain TAV5, microaerophilic and member of phylum Verrucomicrobia, isolated from the hindgut of the Reticulitermes flavipes termite, the most widely distributed subterranean termite in North America. Its genome contains genes associated with methylotrophic competency which code for enzymes that structurally modify lignin. The overall goal of this research was to use TAV5 to modify lignin and boost methane production from MSW. Batch-scale reactors (125 mL) were filled with paper, yard, or wood waste, and four ratios of mixed of waste. Reactors were seeded with different ratios of TAV5 to anaerobic digester (AD) microorganisms (representing landfill anaerobic microorganisms). Based on batch tests, optimal ratios of TAV5 to AD microorganisms were used to seed wastes (mixed, yard, and wood) in 6-gallon reactors. Addition of TAV5 increased methane production from mixed waste, yard waste, and wood, by 49%, 34%, and 297%, respectively. TAV5 decreased acid soluble lignin by 7-39%, depending on waste type. TAV5 grown under aerobic conditions and room temperature (not requiring a heated anaerobic chamber) was found to remain viable and increase methane production under low-level oxygen conditions (1-2%). This finding will potentially lessen costs for growing large volumes of it for seeding landfills.

Hearing status in patients with vitiligo.

Background: Vitiligo is an acquired disorder characterized by depigmented macules and patches that result from a progressive loss of functional melanocytes. During embryogenesis, precursor cells of melanocytes (melanoblasts) migrate not only to the epidermis and hair follicles but also to the leptomeninges, uveal tract of the eye, and inner ear. Thus, it has been proposed that these organs may be involved in vitiligo, as well. Objective: This study was designed to evaluate the frequency and characteristics of hearing loss by means of audiometry and  distortion  product otoaucostic emission (DPOAE) in patients with vitiligo. Methods: Fifty-three patients with vitiligo and 52 age- and sex-matched healthy subjects were enrolled in this case-control study. After a complete otological examination, comprehensive audiological evaluations including pure tone audiometry (PTA) and DPOAE were performed for all participants and the results were compared between the two groups. Results: Neither PTA nor DPOAE showed significant difference between the two groups in any of the evaluated frequencies (0.75-8 KHz). Furthermore, in patient group, there was no association between PTA/DPOAE and age, gender, duration of the disease, presence of halo nevus, type of vitiligo, extent of involvement, and positive family history of vitiligo. Conclusion: Vitiligo patients have normal hearing status.

Cultured Epidermal Melanocyte Transplantation in Vitiligo: A Review Article.

BACKGROUND: The color of the skin is highly heritable but can be influenced by the environments and endocrine factors. Many other factors, sometimes destructive, are also involved in the formation of skin color, which sometimes affects pigmentation patterns. Vitiligo is an autoimmune hypopigmentation painless disorder with appearance of white patches and psychological effects on patients. It is a disease in which melanocytes of the skin are destroyed in certain areas; therefore depigmentation appears. METHODS: We studied more than 60 articles. Several therapeutic methods have been used to return the color of skin in vitiligo. These methods include non-invasive treatment and surgical techniques. Among all these therapies, cell transplantation is an advanced procedure in regenerative medicine. Extraction of melanocytes from normal skin and then their cultivation in the laboratory provides a large number of these cells, the transplanting of which to depigmentation areas stimulates the site to irreversibly produce melanin. RESULTS: The transplantation methods of these cells have been evolved over many years and the methods of producing blister have been changed to the injection of these cells to the target sites. CONCLUSION: In this review, autologous cultured melanocyte transplantation has been considered to be the most viable, safe, and effective method in the history of vitiligo treatments.

Ethnobotany, Phytochemistry and Traditional Uses of Curcuma spp. and Pharmacological Profile of Two Important Species (C. longa and C. zedoaria): A Review.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Curcuma, which is the most important source of curcumin, has been widely used in different traditional medicines. Various species of Curcuma have long been used for several purposes such as healing wounds, liver disorders, jaundice and also as a blood purifier. AIM OF THE STUDY: This review focused on the ethnopharmacological uses and phytochemical aspects of Curcuma. Additionally, in this study, the different properties of two species of Curcuma in Islamic Traditional Medicine (ITM), C. longa and C. zedoaria, as well as their pharmacological aspects in modern medicine are reviewed. MATERIALS AND METHODS: ITM literatures were searched to find Curcuma's applications. Also, electronic databases including PubMed and Scopus were searched to obtain studies giving any in vitro, in vivo or human evidence of the efficacy of C. longa and C. zedoaria in the treatment of different diseases. ChemOffice software was used to find chemical structures. RESULTS: The analysis showed that ethno-medical uses of Curcuma have been recorded for centuries. Approximately, 427 chemical compounds have been isolated and identified from Curcuma spp. This genus is rich in flavonoids, tannins, anthocyanin, phenolic compounds, oil, organic acids and inorganic compounds. Curcumin is one of the main active ingredients in Curcuma which has strong anti-inflammatory and antioxidant effects. Besides, pharmacological studies have indicated wide range of Curcuma's activities, such as hepato-protective, antifungal, antihypertensive and neuroprotective. CONCLUSIONS: In this study, we reviewed various studies conducted on ethno-medicinal, ITM properties and photochemistry of Curcuma spp. Also, pharmacological activities of two species, C. longa and C. zedoaria are summarized. Pre-clinical investigations have demonstrated some of the traditional aspects of Curcuma, such as wound healing, anti-arthritic, anti-tumor and liver protective activities. These could be related to antioxidant and anti-inflammatory properties of Curcuma which might be due to high amounts of phenolic compounds. Curcuma is mentioned to have neural tonic properties in ITM which have been confirmed by some animal studies. Considering various preclinical studies on C. longa and C. zedoaria and their active ingredient, curcumin, randomized controlled trials are warranted to confirm their promise as a clinically effective hepato and neuro-protective agents.