A comparison of iCare and Goldmann applanation tonometry measurements during the COVID-19 pandemic: a retrospective study.

PURPOSE: To evaluate factors associated with differences in intraocular pressure (IOP) readings between iCare and Goldmann applanation tonometry (GAT) in established glaucoma patients. METHODS: This retrospective comparative study included clinical data of 350 eyes from 350 established glaucoma patients who had iCare and GAT IOP measured by an ophthalmic technician and a glaucoma specialist, respectively. The main outcome measure was the difference in IOP measurements of the right eyes with iCare and GAT. RESULTS: The intraclass correlation coefficient (ICC) between GAT and iCare was 0.90. The mean IOP difference between tonometers was - 0.18 ± 2.89 mmHg. Bland-Altman plots indicated a 95% limit of agreement of - 5.8 to 5.5 mmHg. Central corneal thickness (CCT) and age were significantly correlated with the difference in IOPs of the iCare and GAT. GAT-IOP and age were significantly associated with the absolute difference in measured IOP of the two tonometers. The difference in measurements was not significantly associated with prior glaucoma surgery, average global index of optical coherence tomography, axial length, technician years of experience and certification, and IOP range. CONCLUSION: Although there is good agreement between the iCare and GAT mean values, these devices are not interchangeable in glaucoma patients due to the wide range of the limit of agreement.

Angiotensin-converting enzyme as a new immunologic target for the new SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic has affected the daily lives of millions of people worldwide and had caused significant mortality; hence, the assessment of therapeutic options is of great interest. The leading cause of death among COVID-19 patients is acute respiratory distress syndrome caused by hyperinflammation secondary to cytokine release syndrome (CRS). Cytokines, such as tumor necrosis factor-α, interleukin-6, interferon-γ and interleukin-10, are the main mediators of CRS. Based on recent evidence, the angiotensin-converting enzyme (ACE) II is known to be the target of the COVID-19 spike protein, which enables the virus to penetrate human cells. ACE II also possesses an anti-inflammatory role in many pathologies such as cardiovascular disease, hypertension, diabetes mellitus and other conditions, which are the main risk factors of poor prognosis in COVID-19 infection. Changes in tissue ACE II levels are associated with many diseases and hyperinflammatory states, and it is assumed that elevated levels of ACE II could aggravate the course of COVID-19 infection. Therefore, the use of renin-angiotensin-aldosterone system inhibitors (RASis) in COVID-19 patients could be hypothetically considered, though sufficient evidence is not presented by the scientific community. In this work, based on the most recent pieces of evidence, the roles of RAS and RASi in immunologic interactions are addressed. Furthermore, the molecular and immunologic aspects of RASi and their potential significance in COVID-19 are discussed.

Conjugated CAR T cell one step beyond conventional CAR T cell for a promising cancer immunotherapy.

Cancer immunotherapy aims to enhance the immune system reactivity against tumour cells. Chimeric Antigen Receptor (CAR), presented on the surface of the T cells, specifically redirects the cell and demonstrates significant promises in treating patients with different types of haematologic malignancies. Although several cases of improvement have been reported, clinical experiences, such as excessive activity, poor control, toxicity and limited life span of conventional CAR T cells have emerged as treatment challenges associated with this therapeutic strategy. Recently, multiple switchable CAR T platforms have been made to enable better control in a dose-dependent manner, which is correlated to distinct characteristics of different switch molecules. This review aimed at a brief represention of toxicities of the CAR T cells, the obstacles facing tumour treatments especially in solid tumours, and finally providing a framework for classification of the newly developed Conjugated/Split CAR-T cell technologies to overcome difficulties. Overall, Newly developed Conjugated CAR T cells using among with soluble switch molecules seems to be as responsive as the conventional CAR T cells, yet providing many new useful options to effectively overcome limitations and significantly improve patient safety.

Phototoxicity of environmental radiations in human lens: revisiting the pathogenesis of UV-induced cataract.

The magnitude of cataract pathology is indeed significant as it is the principal cause of blindness worldwide. Also, the prominence of this concept escalates with the current aging population. The burden of the disease is more tangible in developing countries than developed ones. Regarding this concern, there is a gap in classifying the pathogenesis of the ultraviolet (UV) radiation-induced cataracts and explaining the possible cellular and subcellular pathways. In this review, we aim to revisit the effect of UV radiation on cataracts categorizing the cellular pathways involved. This may help for better pharmaceutical treatment alternatives and their wide-reaching availability. Also, in the last section, we provide an overview of the protecting agents utilized as UV shields. Further studies are required to enlighten new treatment modalities for UV radiation-induced pathologies in human lens.

Disparities in Eye Care Utilization Among Refugee and Migrant Populations.

Purpose: In this cross-sectional study, we examined refugee/migrant participants' health and eye care utilization compared to controls in San Diego County. Methods: Data were collected from electronic health records (EHRs) at UCSD Health-affiliated medical centers. Through a manual review of EHRs, eligibility criteria to identify a cohort were developed. A total of 64 refugee/migrant participants and 95 control participants matched based on country of origin, age, and sex were included in the analysis. Demographic characteristics, insurance type, and vision/eye care utilization were compared between the two groups. Results: A greater proportion of refugee/migrant participants were more likely to be enrolled in government-sponsored insurance programs, predominantly Medicaid when compared to controls (55% vs. 24%, P = < 0.01). When adjusting for age, history of ophthalmic procedure, and surgery, refugee status was associated with fewer encounters with ophthalmologists in a multivariable linear regression model (coefficient = -1.66 [95% confidence interval [CI] = -2.89 to -0.44], P = 0.009). Conclusions: This study highlights disparities in eye care utilization for refugee/migrant populations. When compared to controls, a larger proportion of refugees/migrants had government-funded insurance, and refugee status was associated with fewer encounters with ophthalmologists. These findings underscore the need for further research on this population to better understand potential healthcare barriers these individuals may encounter. Translational Relevance: This analysis of EHR data illustrates disparities in eye care experienced by refugees/migrants, highlighting potential gaps in care in a vulnerable population.

Persistent Mydriasis Following Gonioscopy-Assisted Transluminal Trabeculotomy.

Herein we describe 2 cases of persistent mydriasis after gonioscopy-assisted transluminal trabeculotomy for open angle glaucoma. Both surgeries were uneventful, but the patients experienced postoperative hyphema and intraocular pressure elevation. They then developed persistent fixed and dilated pupils resistant to pilocarpine that led to intolerable photosensitivity and glare. An iris cerclage pupilloplasty was performed with adequate relief of symptoms in one case.

Association between Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists Exposure and Intraocular Pressure Change.

Objective: This study aims to provide data on the effects of glucagon-like peptide 1 receptor (GLP-1R) agonists on intraocular pressure (IOP). Design: Retrospective cohort study. Subjects Participants and/or Controls: 1247 glaucoma surgery and treatment naïve eyes of 626 patients who were initiated on GLP-1R agonists compared to 1083 glaucoma surgery and treatment naïve eyes of 547 patients who were initiated on other oral antidiabetics. Methods Intervention or Testing: The University of California Health Data Warehouse was queried for patients exposed to GLP-1R agonists or other oral antidiabetics. Index date was defined as the date of first exposure to the medication. Eyes with at least one pre-exposure and one post-exposure tonometry record within 365 days of the index date were included in the analysis. Clinical and laboratory data elements were extracted from the database. Eyes were censored from the analysis upon exposure to glaucoma hypotensive medication or glaucoma surgery. ΔIOP was analyzed using a paired t-test. Regression analysis was conducted using generalized estimating equations (GEE) accounting for inter-eye correlation. Sensitivity analyses were performed to assess the robustness of the findings. Main Outcome Measures: Primary outcome measure was ΔIOP after exposure to the medication. Results: The median age of all included subjects was 66.2 years [IQR=18.3]; 607 (51.7%) were female, and 667 (56.9%) were Caucasian. Median pre-exposure IOP, HbA1c, and BMI were 15.2 mmHg [IQR=3.8], 7.5 [IQR=2.4], and 29.8 [IQR=9.4], respectively. 776 individuals (66.1%) had diabetes, with the median number of active oral antidiabetics being 1.0 [IQR=1.0], and 441 (37.5%) being insulin users. Several pre-exposure characteristics significantly differed between the GLP-1R agonist and the control group. The mean ΔIOP was -0.4±2.8 mmHg (paired t-test p<0.001) and -0.2±3.3 mmHg (paired t-test p = 0.297) in the GLP-1R agonist and other antidiabetics groups, respectively. Pre-exposure IOP was the only independent predictor of ΔIOP in multivariable GEE. Sensitivity analyses yielded similar results. Conclusions: Although GLP-1R agonists were significantly associated with a decrease in IOP in the paired analysis, they were not associated with ΔIOP in multivariable GEE. Moreover, the difference between the ΔIOP in the two groups was small. Future prospective studies following a standardized dose and delivery method may provide further insights.

Empowering Family Glaucoma Risk Communication Using QR-Code-Mediated Online Intervention.

PURPOSE: Attempts at engaging relatives of glaucoma patients in education and screening have had limited success. This study explores the feasibility of an electronic intervention to facilitate direct yet reliable glaucoma risk communication between open-angle glaucoma patients (probands) and their first-degree relatives (FDRs). DESIGN: Prospective survey and assessment of intervention. PARTICIPANTS: Fifty adult probands, engaging 140 FDRs. METHODS: Phase I was an iterative process involving creating a customized website and Quick Response (QR)-code-based intervention designed with input from probands, FDRs of patients, community members, and researchers. In phase II, the intervention was deployed in a clinical setting; this involved recruiting probands who had a smartphone and were willing to use the QR-code to message their FDRs a standard message, including a website link about glaucoma risk in FDRs and the importance of getting examined. Follow-up interviews were conducted with probands 1 to 2 weeks after their clinic visit to assess the impact of the intervention. Demographic data, website analytics, and participant feedback were collected and analyzed. MAIN OUTCOME MEASURES: Increased awareness of glaucoma risk among FDRs and enhanced discussions. RESULTS: At the time of the first interview, probands reported that 70% of the FDRs were aware of the probands' glaucoma diagnosis, but only 26% had undergone glaucoma screening. Ninety percent of probands had no issues using the QR-codes. Website analytics recorded 73 visits from 51 distinct internet protocol addresses (IPs). After receiving the standard message, 95% of FDRs followed up with the probands, actively discussing glaucoma. Of the probands, 84% completed the follow-up interview 1 to 2 weeks after enrollment. Fifty-nine percent of the FDRs were reported to have scheduled screening appointments. The collected feedback revealed that 96% of probands found the intervention helpful, fostering glaucoma discussions with their FDRs and improving probands' comfort level in discussing health issues with FDRs from baseline (very comfortable: 88%, comfortable: 8%, neutral: 2%, and very uncomfortable: 2%) to the follow-up interview (very comfortable: 98% and comfortable: 2%). CONCLUSIONS: This innovative online method of communicating the risk of glaucoma to FDRs of probands prompted and increased the comfort level of familial discussions of glaucoma. More than half of FDRs reported making an appointment to get screened for glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Early Postoperative Aqueous Suppression Therapy and Surgical Outcomes of Ahmed Tube Shunts in Refractory Glaucoma.

PURPOSE: To compare early vs. delayed use of aqueous suppressants on Ahmed glaucoma valve (AGV) outcomes. DESIGN: Single-center retrospective comparative case series. PARTICIPANTS: Patients who underwent AGV surgery at Wills Eye Hospital in the period between 2016 and 2021. METHODS: Retrospective review of AGV surgery at Wills Eye Hospital 2016 to 2021 for refractory glaucoma. Two groups were created: group 1 or those who received early aqueous suppressant therapy in the first 2 weeks postoperatively whenever the intraocular pressure (IOP) was > 10 mmHg, and group 2 or those who received delayed treatment after 2 weeks whenever the IOP exceeded the target pressure. Aqueous suppressant therapy included topical beta blockers, carbonic anhydrase inhibitors, and/or alpha agonists. MAIN OUTCOME MEASURES: The primary outcome measures were the frequency of hypertensive phase (HP) defined as IOP > 21 mmHg in first 3 months after an initial reduction to 21 mmHg or less in the first postoperative week not caused by tube obstruction or retraction, and month-12 surgical failure defined as 5 ≥ IOP > 21 mmHg on 2 consecutive visits, vision decline to no light perception (NLP), or glaucoma reoperation. Secondary outcome measures included changes in visual acuity (VA), IOP, and glaucoma medications at 12 months. Predictive factors for surgical failure were also identified. RESULTS: A total of 407 eyes of 391 patients (260 in group 1, 147 in group 2) with similar baseline characteristics were included. Hypertensive phase was more common in group 2 than 1 (41.5% vs. 18.5%; P < 0.001). At month 12 (N = 303 eyes), group 1 was less likely to fail than group 2 (21.2% vs. 36.8%, P = 0.003). Multivariate regression analysis showed that HP (odds ratio [OR] = 10.47, P < 0.001), delayed aqueous suppression use (OR = 2.17, P = 0.003), and lower baseline VA (OR = 1.56, P = 0.015) were the strongest predictors of month-12 failure. CONCLUSIONS: Early use of aqueous suppressants may lower the risk of HP and improve AGV outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Long-Term Surgical Outcomes of Glaucoma Drainage Implants in Eyes with Preoperative Intraocular Pressure Less than 19 mmHg.

Background: This retrospective review reports on patients who underwent glaucoma drainage implant (GDI) surgery and had baseline intraocular pressure (IOP) of ≤18 mmHg with at least one year of follow-up. Methods: Clinical data of 67 eyes of 67 patients were collected from patients' charts, and the outcomes of GDI were evaluated until 7 years. GDI failure was defined as IOP reduction of less than 20% from the baseline at two consecutive visits three months after surgery, decline to no light perception, or if additional glaucoma surgery was performed. Results: The average age was 65.9 ± 13.2 years. Most cases were male (52.2%), White (53.7%), and had primary open-angle glaucoma (62.7%). Forty-four eyes had prior glaucoma surgery (68.6%) and 46 (68.6%) had severe glaucoma. Though postoperative (postop) IOP changes were insignificant, the average postop number of medications dropped from 2.4 ± 1.4 to 1.9 ± 1.2 medications two years after surgery (p = 0.0451). Postop complications (23.9%) included GDI exposure (7.5%), inflammation (4.5%), shallow anterior chamber (4.5%), and strabismus (1.5%). Hypotony was observed in 4 eyes (5.9%), none of which developed hypotony maculopathy. The cumulative one-year failure rate was 56.7%, most of which were due to failure to lower IOP. Conclusion: In patients with baseline IOP ≤18 mmHg who had GDI surgery, though the change in IOP was not statistically significant, the number of medications dropped and visual field progression slowed in a subset of patients with adequate perimetric data. Due to a relatively high rate of complications and limited effectiveness in lowering IOP, GDI should be cautiously used in these eyes.

Intraocular pressure profile following selective laser trabeculoplasty in pigmentary and primary open-angle glaucoma.

PURPOSE: To compare the intraocular pressure (IOP) profile and the incidence of IOP spikes following selective laser trabeculoplasty (SLT) between pigmentary glaucoma (PG) and primary open-angle glaucoma (POAG). MATERIALS AND METHODS: Retrospective comparative study of 65 PG eyes of 51 patients matched with 65 POAG eyes of 65 patients who received SLT. Matching was done based on age, gender, glaucoma severity, pre-laser IOP, and number of medications. Post-SLT IOP spike was defined as IOP elevation ≥5mmHg, 30-45 min after the laser. RESULTS: In PG and POAG groups, the average age was 62.33 ± 9.18 and 62.58 ± 9.19 years (p = 0.95). The glaucoma severity (p = 0.708), baseline IOP (PG = 21.61 ± 1.34mmHg vs. POAG = 21.13 ± 5.09mmHg, p = 0.943), and number of topical glaucoma medications(PG = 2.34 ± 1.34 vs. POAG = 2.1 ± 1.41, p = 0.342) were comparable. More PG patients were on oral acetazolamide (PG = 26.15% vs. POAG = 1.5%, p < 0.001). Average logMAR visual acuity was significantly higher in the POAG group (0.207 ± 0.3 vs. 0.192 ± 0.37, p = 0.012). Eyes with PG received lower laser energy (POAG = 63.65 ± 22.03 mJ vs. PG = 43.71 ± 25.68 mJ, p < 0.001). IOP spikes were recorded in 5 PG eyes (7.6%) and none in the POAG group (p = 0.058). Failure rates were similar (PG = 50.7% and POAG = 43.1%, p = 0.205). In multivariable analysis, only pre-laser IOP (coefficient = 2.154 [CI: 0.765-3.543], p = 0.003) was a significant predictor of IOP change percentage after 12 months. CONCLUSIONS: SLT was comparably effective in both PG and POAG. IOP spikes were observed only in the PG group, though the total laser energy was lower in this group compared with POAG.

10-Year Clinical Outcomes of Tube Shunt Surgery at a Tertiary Care Center.

PURPOSE: To report 10-year clinical outcomes of tube shunt (TS) surgery at a tertiary care center. DESIGN: Retrospective cohort study. METHODS: Eyes were included that underwent a first TS surgery between January 2005 and December 2011 at a tertiary referral eye hospital and with at least 10 years of follow-up. Demographic and clinical data were collected. Failure was defined as reoperation to lower intraocular pressure (IOP), IOP > 80% of baseline for two consecutive visits, or progression to no light perception. RESULTS: Eighty-five eyes of 78 patients were included in the Study Group; 89 eyes were selected as a Comparison Group. Mean follow-up was 11.9 ± 1.7 years. Fifty-one valved (60%), 25 non-valved (29%), and nine unknown (11%) TS were placed. At the final visit, mean IOP was reduced from 29.2 ± 10.4 mmHg on 3.1 ± 1.2 medications to 12.6 ± 5.8 mmHg on 2.2 ± 1.4 (p<0.001 for each). Forty-eight eyes (56%) failed; 29 eyes (34%) underwent additional glaucoma surgery; eight eyes (10%) progressed to no light perception; and 34 eyes (40%) also required TS revision. Best corrected visual acuity (BCVA) logMAR (minimal angle of resolution) worsened from 0.8 ± 0.7 (20/125) to 1.4 ± 1.0 (20/500) at the last visit (p<0.001). Average visual field MD was -13.9 ± 7.5 dB at baseline and -17.0 ± 7.0 dB at last follow-up (P=0.0605). CONCLUSIONS: Many eyes maintained IOP control 10 years following TS, but 56% met failure criteria, 39% had substantial vision loss, and 34% underwent additional surgery. Outcomes did not differ with TS model. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Endoscopic, laboratory, and clinical findings and outcomes of caustic ingestion in adults; a retrospective study.

Aim: Compared to the prevalence and complications, there is still limited evidence in this regard. Background: With an incidence rate of 200,000 cases annually and the induction of numerous complications, caustic ingestion imposes a significant burden on the healthcare system. Apart from being fatal in some cases, this injury affects its victims' quality of life as it is followed by many gastrointestinal problems. This injury mainly occurs accidentally among children, whereas in adults, it often occurs with suicidal intentions. Despite recent advances in internal medicine, gastroenterology, and toxicology, this type of injury remains a debilitating and, in some cases, fatal disorder for its victims. Methods: This study retrospectively evaluated the clinical, laboratory, and endoscopic findings of 150 patients admitted to a referral center of toxicology and forensic medicine and assessed factors associated with each type of injury. Results: The findings indicated a mortality rate as high as 7.3% in this population. Age, pH, and previous medical conditions were associated with more complications. Higher degrees of injury were also significantly associated with higher mortality. No significant difference was observed between types of corrosive substances. Conclusion: It seems that the most effective intervention for controlling caustic ingestion injuries would be psychiatric support, primary healthcare, and household education.

Doped-carbon dots: Recent advances in their biosensing, bioimaging and therapy applications.

As a fascinating class of fluorescent carbon dots (CDs), doped-CDs are now sparked intense research interest, particularly in the diverse fields of biomedical applications due to their unique advantages, including low toxicity, physicochemical, photostability, excellent biocompatibility, and so on. In this review, we have summarized the most recent developments in the literature regarding the employment of doped-CDs for pharmaceutical and medical applications, which are published over approximately the past five years. Accordingly, we discuss the toxicity and optical properties of these nanomaterials. Beyond the presentation of successful examples of the application of these multifunctional nanoparticles in photothermal therapy, photodynamic therapy, and antibacterial activity, we further highlight their application in the cellular labeling, dual imaging, and in vitro and in vivo bioimaging by use of fluorescent-, photoacoustic-, magnetic-, and computed tomography (CT)-imaging. The potency of doped-CDs was also described in the biosensing of ions, small molecules, and drugs in biological samples or inside the cells. Finally, the advantages, disadvantages, and common limitations of doped-CD technologies are reviewed, along with the future prospects in biomedical research. Therefore, this review provides a concise insight into the current developments and challenges in the field of doped-CDs, especially for biological and biomedical researchers.

Adenosine: The common target between cancer immunotherapy and glaucoma in the eye.

Adenosine, an endogenous purine nucleoside, is a well-known actor of the immune system and the inflammatory response both in physiologic and pathologic conditions. By acting upon particular, G-protein coupled adenosine receptors, i.e., A1, A2- a & b, and A3 receptors mediate a variety of intracellular and immunomodulatory actions. Several studies have elucidated Adenosine's effect and its up-and downstream molecules and enzymes on the anti-tumor response against several types of cancers. We have also targeted a couple of molecules to manipulate this pathway and get the immune system's desired response in our previous experiences. Besides, the outgrowth of the studies on ocular Adenosine in recent years has significantly enhanced the knowledge about Adenosine and its role in ocular immunology and the inflammatory response of the eye. Glaucoma is the second leading cause of blindness globally, and the recent application of Adenosine and its derivatives has shown the critical role of the adenosine pathway in its pathophysiology. However, despite a very promising background, the phase III clinical trial of Trabodenoson failed to achieve the non-inferiority goals of the study. In this review, we discuss different aspects of the abovementioned pathway in ophthalmology and ocular immunology; following a brief evaluation of the current immunotherapeutic strategies, we try to elucidate the links between cancer immunotherapy and glaucoma in order to introduce novel therapeutic targets for glaucoma.

Non-coding RNAs role in intracranial aneurysm: General principles with focus on inflammation.

Intracranial aneurysm (IA) is one of the most challenging vascular lesions in the brain for clinicians. It was reported that 1%-6% of the world's population is affected by IAs. Owing to serious complications arising from these lesions, much attention has been paid to better understand their pathophysiology. Non-coding RNAs including short non-coding RNAs and long non-coding RNAs, have critical roles in modulating physiologic and pathological processes. These RNAs are emerging as new fundamental regulators of gene expression, are related with the progression of IA. Non-coding RNAs act via multiple mechanisms and be involved in vascular development, growth and remodeling. Furthermore, these molecules are involved in the regulation of inflammation, a key process in the formation and rupture of IA. Studying non-coding RNAs can yield a hypothetical mechanism for better understanding IA. The present study aims to focus on the role of these non-coding RNAs in the pathogenesis of IA.

Different T cell related immunological profiles in COVID-19 patients compared to healthy controls.

In various pathological conditions, cellular immunity plays an important role in immune responses. Amongimmunecells, T lymphocytes pdomotecellular and humoralresponses as well as innate immunity. Therefore, careful investigation of these cells has a significant impact on accurate knowledge in COVID-19diseasepathogenesis. In current research, the frequency and function of various T lymphocytes involved in immune responses examined in SARS-CoV-2 patients with various disease severity compared to normal subjects. In order to make an accurate comparison among patients with various disease severity, this study was performed on asymptomatic recovered cases (n = 20), ICU hospitalized patients (n = 30), non-ICU hospitalized patients (n = 30), and normal subjects (n = 20). To precisely evaluate T cells activity following purification, their cytokine secretion activity was examined. Similarly, immediately after purification of Treg cells, their inhibitory activity on T cells was investigated. The results showed that COVID-19 patients with severe disease (ICU hospitalized patients) not only had a remarkable increase in Th1 and Th17 but also a considerable decrease in Th2 and Treg cells. More importantly, as the IL-17 and IFN-γ secretion was sharply increased in severe disease, the secretion of IL-10 and IL-4 was decreased. Furthermore, the inhibitory activity of Treg cells was reduced in severe disease patients in comparison to other groups. In severe COVID-19 disease, current findings indicate when the inflammatory arm of cellular immunity is significantly increased, a considerable reduction in anti-inflammatory and regulatory arm occurred.

Targeting PI3K/Akt/mTOR signaling pathway by polyphenols: Implication for cancer therapy.

Cancer is one of the biggest challenges facing medicine and its cure is regarded to be the Holy Grail of medicine. Therapy in cancer is consisted as various artificial cytotoxic agents and radiotherapy, and recently immunotherapy. Recently much attention has been directed to the use of natural occurring agents in cancer therapy. One of the main group of agents utilized in this regard is polyphenols which are found abundantly in berries, fruits and vegetables. Polyphenols show to exert direct and indirect effects in progression of cancer, angiogenesis, proliferation and enhancing resistance to treatment. One of the cellular pathways commonly affected by polyphenols is PI3K/Akt/mTOR pathway, which has far ranging effects on multiple key aspects of cellular growth, metabolism and death. In this review article, evidence regarding the biology of polyphenols in cancer via PI3K/Akt/mTOR pathway is discussed and their application on cancer pathophysiology in various types of human malignancies is shown.

Tumor associated macrophages in the molecular pathogenesis of ovarian cancer.

The tumor microenvironment is a critical factor that enhances cancer progression, drug resistance, and failure of therapeutic approaches. Several cellular and non-cellular factors are involved in cancer promotion. Among the several cell populations in the tumor microenvironment, macrophages, as one of the most abundant innate immune cells within the tumor milieu, have attracted extensive attention among several researchers because of their critical role in innate pathophysiology of multiple disorders, as well as ovarian cancer. High plasticity and consequent high ability to adapt to environmental alternations by adjusting their cellular metabolism and immunological phenotype is the notable characteristic of macrophages. Therefore, the critical function of tumor-associated macrophages in ovarian cancer is highlighted in the growing body of recent studies. In this article, we will comprehensively focus on significant impacts of the macrophages on ovarian cancer progression, by discussing the role of macrophages as one of the fundamental immune cells present in tumor milieu, in metabolic reprogramming of transformed cells, and involvement of these cells in the ovarian cancer initiation, progression, invasion, and angiogenesis. Moreover, we will summarise recent studies evaluating the effects of targeting macrophages in ovarian cancer.