Gynecological cancer confers an enormous burden among women worldwide. Accumulating evidence points to the role of phytochemicals in preventing cervical, endometrial, and ovarian cancer. Experimental studies emphasize the chemopreventive and therapeutic potential of plant-derived substances by inhibiting the early stages of carcinogenesis or improving the efficacy of traditional chemotherapeutic agents. Moreover, a number of epidemiological studies have investigated associations between a plant-based diet and cancer risk. This literature review summarizes the current knowledge on the phytochemicals with proven antitumor activity, emphasizing their effectiveness and mechanism of action in gynecological cancer.

Methotrexate (MTX) is a commonly used antimetabolite, which inhibits folate and DNA synthesis to be effective in the treatment of various malignancies. However, MTX therapy is hindered by the lack of target tumor selectivity. We have designed, synthesized and evaluated a novel glucose–methotrexate conjugate (GLU–MTX) both in vitro and in vivo, in which a cleavable linkage allows intracellular MTX release after selective uptake through glucose transporter−1 (GLUT1). GLU–MTX inhibited the growth of colorectal (DLD-1), breast (MCF-7) and lung (A427) adenocarcinomas, squamous cell carcinoma (SCC-25), osteosarcoma (MG63) cell lines, but not in WI-38 healthy fibroblasts. In tumor cells, GLU–MTX uptake increased 17-fold compared to unconjugated MTX. 4,6-O-ethylidene-α-D-glucose (EDG), a GLUT1 inhibitor, significantly interfered with GLU–MTX induced growth inhibition, suggesting a glucose-mediated drug uptake. Glu-MTX also caused significant tumor growth delay in vivo in breast cancer-bearing mice. These results show that our GLUT-MTX conjugate can be selectively uptake by a range of tumor cells to cause their significant growth inhibition in vitro, which was also confirmed in a breast cancer model in vivo. GLUT1 inhibitor EDG interfered with these effects verifying the selective drug uptake. Accordingly, GLU–MTX offers a considerable tumor selectivity and may offer cancer growth inhibition at reduced toxicity.

The prevailing COVID-19 pandemic has dramatically affected the mental health and well-being of individuals. This cross-sectional study aimed to assess the perceived fear of COVID-19 among older adults in Poland and identify subpopulations with the highest risk of potential mental health disorders. The study was conducted in November–December 2020 on 500 people aged ≥60 years (mean M = 67.9, standard deviation SD = 4.2). In order to collect information on participants’ characteristics and COVID-19-related information, they were asked to complete a questionnaire based on recorded telephone calls. Perceived fear of COVID-19 was measured using Fear of COVID-19 Scale (FCV-19S), which ranges from 7 to 35. Multiple linear regression was performed to identify factors associated with the perceived fear of COVID-19. Our results showed that the highest level of fear of COVID-19 infection was observed among women (p = 0.025) and patients taking anticoagulants (p = 0.004). Moreover, older adults with higher anxiety levels were more likely to be fearful of COVID-19 (according to the GAS-10 scale; p < 0.001). These findings may help policy makers and healthcare workers to adapt and implement better mental health strategies to help the elderly fight fear and anxiety during the prevailing pandemic.

Given the rising rate of opioid-related adverse drug events during postsurgical pain management, a nonpharmacologic therapy that could decrease analgesic medication requirements would be of immense value. We designed a prospective, placebo-and-randomized controlled trial to assess the clinical effect of transcutaneous acupoint electrical stimulation (TEAS) on the postoperative patient-controlled analgesia (PCA) requirement for morphine, as well as side effects and recovery profile after inguinal hernia repair. Seventy-one subjects undergoing inguinal hernia repair with a standardized anesthetic technique were randomly assigned to one of three analgesic treatment regimens: PCA + TEAS (n = 24); PCA + sham-TEAS (no electrical stimulation) (n = 24), and PCA only (n = 23). The postoperative PCA requirement, pain scores, opioid-related side effects, and blood cortisol levels were recorded. TEAS treatment resulted in a twofold decrease in the analgesic requirement and decreased pain level reported by the patients. In addition, a significant reduction of cortisol level was reported in the TEAS group at 24 h postoperatively compared to the sham and control groups. We conclude that TEAS is a safe and effective option for reducing analgesic consumption and postoperative pain following inguinal hernia repair.

Due to the prevailing pandemic of the coronavirus disease COVID-19, we are experiencing emotional and social isolation, which negatively affects mental and physical health, particularly among the elderly population. In this study, we performed a cross-sectional analysis based on computer-assisted telephone interviews of 500 Polish adults aged 60 years or older in order to determine the impact of the SARS-CoV-2 pandemic on the older population’s behavior, life activity, and delivery of healthcare services. According to our study, COVID-19 infection entailed a substantial change in older people’s behavior. Over 50%, nearly 80%, and more than 25% of the surveyed participants reduced their social, recreational, and professional activities, respectively. The most significant change in senior’s behavior due to the fear of COVID-19 infection was observed in patients (1) with cardiac and pulmonary problems, (2) being on multi-drug therapy, (3) vaccinated against influenza, and (4) with several mental difficulties including loneliness, social isolation, and depression. Furthermore, we demonstrated that 10% of participants canceled planned hospitalization due to the fear of COVID-19 infection. This was observed primarily in patients suffering from chronic heart and lung diseases, vaccinated against influenza, exhibiting the reluctance to carry out more complex daily activities, and with a higher level of anxiety, social loneliness, and malnutrition. Thus, these groups of seniors require more attention; hence, we propose telemedicine as a strategy directed to them that provides clinical healthcare and information regarding measurements, control, and protection against SARS-CoV-2 during the prevailing COVID-19 pandemic. We believe this strategy may improve treatment outcomes, reduce comorbidities-related complications and unnecessary hospitalizations.

The oxygen and nutrient-deprived tumor microenvironment is considered a key mechanism responsible for cancer resistance to chemotherapy. Methotrexate (MTX) is a widely incorporated chemotherapeutic agent employed in the treatment of several malignancies. However, drug resistance and systemic toxicity limit the curative effect in most cases. The present work aimed to design, synthesize, and biologically evaluate a novel glucose-methotrexate conjugate (Glu-MTX). Our study showed that Glu-MTX exerts an increased cytotoxic effect on cancer cells in comparison to MTX in hypoxia (1% O₂) and glucose starvation conditions. Furthermore, Glu-MTX was found to inhibit the proliferation and migration of cancer cells more effectively than MTX does. Our results demonstrate that the conjugation of MTX to glucose led to an increase in potency against malignant cells under oxygen and nutrient stress. The observations shed light on a potential therapeutic approach to overcome chemoresistance in cancer.