Biological Role, Mechanism of Action and the Importance of Interleukins in Kidney Diseases

Each year, the number of patients who are diagnosed with kidney disease too late is increasing, which leads to permanent renal failure. This growing problem affects people of every age, sex and origin, and its full etiopathogenesis is not fully understood, although the involvement of genetic susceptibility, infections, immune disorders or high blood pressure is suggested. Difficulties in making a correct and quick diagnosis are caused by the lack of research on early molecular markers, as well as educational and preventive activities among the public, which leads to the late detection of kidney diseases. An important role in the homeostasis and disease progression, including kidney diseases, is attributed to interleukins, which perform several biological functions and interact with other cells and tissues of the body. The aim of this article was to systematize the knowledge about the biological functions performed by interleukins in humans and their involvement in kidney diseases development. In our work, we took into account the role of interleukins in acute and chronic kidney disease and kidney transplantation.

Analysis of main statistical indicators of oral and pharyngeal cancer in the Republic of Uzbekistan

Relevance: According to GLOBOCAN data for 2020, oral and pharyngeal cancer ranked 25th in mortality (98 412 cases, 0.5% of all cancer deaths) and 26th in the number of diagnosed new cases (48 143 cases, 0.5% of all new cancer cases) in the world. Oral and pharyngeal cancer incidence is growing steadily globally and in the Republic of Uzbekistan. Oral and pharyngeal cancer ranks 16th in the structure of cancer incidence in the Republic of Uzbekistan, with a rate of 1.8 per 100 000 people. The purpose of the study was to analyze the main statistical indicators for tumors of the oral cavity and pharynx in the Republic of Uzbekistan in 2015-2021. Methods: We analyzed the main statistical indicators for tumors of the oral cavity and pharynx in the Republic of Uzbekistan for 2015- 2020 obtained from the Reporting Form #7 “Information about malignant neoplasms cases.” Results: Over the past six years, the incidence rate per 100,000 people has increased from 1.4 in 2015 to 1.8 in 2020. In 2015-2020, in the Republic of Uzbekistan, 2,240 patients died from malignant neoplasms of the oral cavity and pharynx. The mortality rate per 100,000 people decreased from 1.4 in 2015 to 1.2 in 2020. Conclusions: Tumors of the oral cavity and pharynx rank 16th in the structure of cancer incidence in the Republic of Uzbekistan and tend to grow. A recent increase in oral and pharyngeal cancer incidence and its late detection could be explained by worsening detection and diagnostics. The stabilization of oral and pharyngeal cancer mortality results in socio-economic losses for the Republic. The provided statistical data is the basis for improving the indicators of incidence and mortality related to oral and pharyngeal cancer in the Republic of Uzbekistan

Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by early metastasis, late detection, and poor prognosis. Progress towards effective therapy has been slow despite significant efforts. Novel treatment approaches are desperately needed and autophagy, an evolutionary conserved process through which proteins and organelles are recycled for use as alternative energy sources, may represent one such target. Although incompletely understood, there is growing evidence suggesting that autophagy may play a role in PDAC carcinogenesis, metastasis, and survival. Early clinical trials involving autophagy inhibiting agents, either alone or in combination with chemotherapy, have been disappointing. Recently, evidence has demonstrated synergy between the MAPK pathway and autophagy inhibitors in PDAC, suggesting a promising therapeutic intervention. In addition, novel agents, such as ONC212, have preclinical activity in pancreatic cancer, in part through autophagy inhibition. We discuss autophagy in PDAC tumorigenesis, metabolism, modulation of the immune response, and preclinical and clinical data with selected autophagy modulators as therapeutics.

Impact of Unintended Initial Dissection of the Posterior Plane on Surgery Time During Small Incision Lenticule Extraction Surgery

Background: To study the impact of unintended initial dissection of the posterior plane (UIDPP) on operation time and surgical outcomes during small incision lenticule extraction (SMILE) surgery.Methods: Based on the SMILE procedure video, the operating eyes were assigned to the normal and UIDPP groups according to the presence or absence of UIDPP signals during surgery. The UIDPP group was further separated into early and late detection. Patient's demographic data, preoperative evaluation data, operation time and postoperative outcomes were collected.Results: Sixty-six patients who underwent SMILE were included, with 24 patients with UIDPP (13 in the early detection group and 11 in the late group). The optical zone was smaller (median 6.5 vs. 6.6, P=0.007), and the operation time was longer (median, 189.5 vs. 91.0 s, P<0.001) in the UIDPP group compared with controls. There were significant differences in operation time between the late detection group and early detection group (median, 489.0 vs. 139.0 s, P<0.05) and between the late detection group and normal group (489.0 vs. 91.0 s, P<0.05), while the optical zone was different only between the late detection and normal groups (median, 6.6 vs. 6.5, P<0.05). Conclusion: The occurrence of UIDPP will increase the surgery time of SMILE. Detecting IUDPP earlier could help shorten the operation time.

Determinants of late detection and advanced-stage diagnosis of breast cancer in Nigeria

Late detection of Breast cancer(BC) and progressing with advanced-stage diagnosis after early detection contribute differently to the challenges of managing BC in Africa. Understanding the difference may improve cancer education programs and their effectiveness. Objective To describe the risk factors for late detection and advanced-stage diagnosis among patients who detected their BC early. Method Using secondary data, we analyzed the impact of socio-demographic factors, premorbid experience, BC knowledge, and health-seeking pattern on the risk of late detection and advanced-stage diagnosis after early BC detection. Test of statistical significance in SPSS and EasyR was set at 5% using Sign-test, chi-square tests (of independence and goodness of fit), odds ratio, or risk ratio as appropriate. Result Most socio-demographic factors did not affect detection size or risk of disease progression in the 405 records analyzed. High BC knowledge, p-value = 0.001, and practicing breast self-examination (BSE) increased early detection, p-value = 0.04, with a higher probability (OR 1.6 (95% CI 1.1–2.5) of detecting <2cm lesions. Visiting alternative care (RR 1.5(95% CI 1.2–1.9), low BC knowledge (RR 1.3(95% CI 1.1–1.9), and registering concerns for hospital care increased the risk of advanced-stage diagnosis after early detection (64% (95% CI 55–72)). Adhering to the monthly BSE schedule reduced the risk of advanced-stage diagnosis by -25% (95% CI -49, -1.1) in the presence of socioeconomic barriers. Conclusion Strategies to increase BC knowledge and BSE may help BC downstaging, especially among women with common barriers to early diagnosis.

siRNA Nanoparticle Targeting PD-L1 Activates Tumor Immunity and Abrogates Pancreatic Cancer Growth in Humanized Preclinical Model

Pancreatic cancer is characterized by late detection, frequent drug resistance, and a highly metastatic nature, leading to poor prognosis. Antibody-based immunotherapy showed limited success for pancreatic cancer, partly owing to the low delivery rate of the drug into the tumor. Herein, we describe a poly(lactic-co-glycolic acid;PLGA)-based siRNA nanoparticle targeting PD-L1 (siPD-L1@PLGA). The siPD-L1@PLGA exhibited efficient knockdown of PD-L1 in cancer cells, without affecting the cell viability up to 6 mg/mL. Further, 99.2% of PDAC cells uptake the nanoparticle and successfully blocked the IFN-gamma-mediated PD-L1 induction. Consistently, the siPD-L1@PLGA sensitized cancer cells to antigen-specific immune cells, as exemplified by Ovalbumin-targeting T cells. To evaluate its efficacy in vivo, we adopted a pancreatic PDX model in humanized mice, generated by grafting CD34+ hematopoeitic stem cells onto NSG mice. The siPD-L1@PLGA significantly suppressed pancreatic tumor growth in this model with upregulated IFN-gamma positive CD8 T cells, leading to more apoptotic tumor cells. Multiplex immunofluorescence analysis exhibited comparable immune cell compositions in control and siPD-L1@PLGA-treated tumors. However, we found higher Granzyme B expression in the siPD-L1@PLGA-treated tumors, suggesting higher activity of NK or cytotoxic T cells. Based on these results, we propose the application of siPD-L1@PLGA as an immunotherapeutic agent for pancreatic cancer.