Novel Entropy-Based Phylogenetic Algorithm: A New Approach for Classifying SARS-CoV-2 Variants.

The SARS-CoV-2 virus, the causative agent of COVID-19, is known for its genetic diversity. Virus variants of concern (VOCs) as well as variants of interest (VOIs) are classified by the World Health Organization (WHO) according to their potential risk to global health. This study seeks to enhance the identification and classification of such variants by developing a novel bioinformatics criterion centered on the virus's spike protein (SP1), a key player in host cell entry, immune response, and a mutational hotspot. To achieve this, we pioneered a unique phylogenetic algorithm which calculates EIIP-entropy as a distance measure based on the distribution of the electron-ion interaction potential (EIIP) of amino acids in SP1. This method offers a comprehensive, scalable, and rapid approach to analyze large genomic data sets and predict the impact of specific mutations. This innovative approach provides a robust tool for classifying emergent SARS-CoV-2 variants into potential VOCs or VOIs. It could significantly augment surveillance efforts and understanding of variant characteristics, while also offering potential applicability to the analysis and classification of other emerging viral pathogens and enhancing global readiness against emerging and re-emerging viral pathogens.

In Silico Exploration of CD200 as a Therapeutic Target for COVID-19.

SARS-CoV-2, the pathogen causing COVID-19, continues to pose a significant threat to public health and has had major economic implications. Developing safe and effective vaccines and therapies offers a path forward for overcoming the COVID-19 pandemic. The presented study, performed by using the informational spectrum method (ISM), representing an electronic biology-based tool for analysis of protein-protein interactions, identified the highly conserved region of spike protein (SP) from SARS-CoV-2 virus, which is essential for recognition and targeting between the virus and its protein interactors on the target cells. This domain is suggested as a promising target for the drug therapy and vaccines, which could be effective against all currently circulating variants of SARS-CoV-2 viruses. The analysis of the virus/host interaction, performed by the ISM, also revealed OX-2 membrane glycoprotein (CD200) as a possible interactor of SP, which could serve as a novel therapeutic target for COVID-19 disease.

Simple Theoretical Criterion for Selection of Natural Compounds with Anti-COVID-19 Activity.

BACKGROUND: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the leading threat to global health. An effective antiviral could not only help those still vulnerable to the virus but could be a critical treatment if a virus emerges toward evading coronavirus disease 2019 (COVID-19) vaccines. Despite the significant efforts to test already-approved drugs for their potential to kill the virus, researchers found very few actually worked. METHODS: The present report uses the electronic molecular descriptors, the quasi-valence number (AQVN), and the electron-ion interaction potential (EIIP), for the analysis of natural compounds with proven therapeutic activity against the COVID-19. RESULTS: Based on the analysis of the electronic properties of natural compounds which are effective against SARS-CoV-2 virus the simple theoretical criterion for the selection of candidate compounds for the treatment of COVID-19 is proposed. CONCLUSIONS: The proposed theoretical criterion can be used for the identification and optimization of new lead compounds for the treatment of the COVID-19 disease and for the selection of the food and food supplements which could have a beneficial effect on COVID-19 patients.

A simple method for calculation of basic molecular properties of nutrients and their use as a criterion for a healthy diet.

Background: Healthy nutrition is vital for good health and well-being. Despite the important role of a healthy nutritional diet, recommendations for healthy eating remain elusive and are mainly based on general properties of nutrients. The present study proposes an improved characterization of the molecular characteristics of nutrients, which are important for biological functions and can be useful in describing a healthy diet. Methods: We investigated the electronic properties of some known nutrient ingredients. In this analysis, we used the average quasi valence number (AQVN) and the electron-ion interaction potential (EIIP), which are molecular descriptors that represent the basic electronic properties of organic molecules.   Results: Our results show that most nutrients can be represented by specific groups of organic compounds according to their basic electronic properties, and these differ from the vast majority of known chemicals. Based on this finding, we have proposed a simple criterion for the selection of food components for healthy nutrition. Discussion: Further studies on the electronic properties of nutrients could serve as a basis for better understanding of their biological functions.

Can natural antibodies to VIP or VIP-like HIV-1 glycoprotein facilitate prevention and supportive treatment of breast cancer?

OBJECTIVES: The incidence of non-AIDS-defining cancer is remarkably higher in HIV-infected than in the general population. In contrast, breast cancer risk is significantly reduced in the HIV-infected population. The molecular mechanisms underlying the phenomenon of suppression of breast cancer in the HIV-infected population may serve as a basis for development of a new platform for prevention and treatment of breast cancer. HYPOTHESIS: Various evidences indicate that vasoactive intestinal peptide (VIP) plays an important role in growth, and differentiation of breast cancer. We previously showed (i) that natural antibodies recognizing VIP and the gp120-derived peptide NTM significantly contribute to the control of HIV disease progression by suppression of VIP-like activity of HIV-1 gp120 and (ii) that physical exercise stimulates production of these natural antibodies. These findings suggest that natural anti-VIP/NTM antibodies could contribute to a decrease of breast cancer in the HIV-infected population by suppression of VIP, which may play a pro/oncogenic function. Aerobic exercise which stimulates production of anti-VIP/NTM antibodies could be used as prevention and supportive treatment of breast cancer. IMPACT: Immunotherapy based on natural anti-VIP/NTM antibodies could serve as an effective adjunct therapy for the treatment of breast cancer. Similarly, aerobic exercise, which stimulates production of these antibodies, should be considered as an inexpensive and safe preventive and supportive breast cancer therapy. Natural anti-VIP/NTM antibodies also represent promising prognostic marker for breast cancer.

Physical activity and natural anti-VIP antibodies: potential role in breast and prostate cancer therapy.

BACKGROUND: There is convincing evidence from numerous clinical and epidemiological studies that physical activity can reduce the risk for breast and prostate cancer. The biological mechanisms underlying this phenomenon remain elusive. Herein we suggest a role for naturally produced antibodies reactive with the vasoactive intestinal peptide (VIP) in the suppression of breast and prostate cancer, which we believe could offer a possible molecular mechanism underlying control of these cancers by physical exercise. METHODOLOGY AND RESULTS: We found that sera from individuals having breast and prostate cancers have decreased titers of VIP natural antibodies as demonstrated by a lower reactivity against peptide NTM1, having similar informational and structural properties as VIP. In contrast, sera collected from elite athletes, exhibited titers of natural NTM1-reactive antibodies that are significantly increased, suggesting that physical activity boosts production of these antibodies. SIGNIFICANCE: Presented results suggest that physical exercise stimulates production of natural anti-VIP antibodies and likely results in suppression of VIP. This, in turn, may play a protective role against breast and prostate cancers. Physical exercise should be further investigated as a potential tool in the treatment of these diseases.

[Venous thromboembolism and oral contraception].

INTRODUCTION: Because of their safety and efficacy oral contraceptives are available without prescription in many countries. Monophasic combined oral contraceptives are a combination of estrogen and progestin taken in constant amounts. VENOUS THROMBOEMBOLISM: Combined oral contraceptives slightly increase the risk of venous thromboemolism, but this event is very rare among non-pregnant women of reproductive age. The absolute risk rises with age, obesity, recent surgery and certain forms of thrombophilia. The estrogen component of combined oral contraceptives increases the synthesis of several coagulation factors in a dose-dependent manner. Changes of most of these parameters are very small and there is no evidence that they have any effect upon the clinical risk of developing venous thrombosis. If a woman has an inherited coagulation disorder that increases her risk of developing thrombosis, the risk is increased several fold if she ingests estrogen containing oral contraception. CONCLUSION: The increased risk of venous thromboembolism associated with combined oral contraceptives should have little impact on healthy women, but may have substantial impact on women with a history of thromboembolism. Combined oral contraceptive use increases the risk of venous thromboembolosm in a dose-dependent manner. The absolute risk of venous thromboembolism rises with age, obesity, recent surgery and certain forms of thrombophilia, as well.

[The risk of breast cervical, endometrial and ovarian cancer in oral contraceptive users].

INTRODUCTION: Oral contraceptives, mainly combined monophasic pills, are widely used by young women who expect their physicians to prescribe them safe drugs which will not harm their health and which will simplify their life. Numerous epidemiologic studies have been performed to determine the relation between oral contraceptive use and the development of neoplasms. BREAST CANCER: An increased incidence of breast cancer has occurred simultaneously with the growing use of oral contraceptives. The possibility of a link between the oral contraceptive use and breast cancer has led to intensive research, but studies have provided inconsistent results causing confusion among clinicians. It was noticed that the risk of breast cancer was slightly elevated in current and recent young oral contraceptives users. That finding could be influenced by a detection bias or could be due to the biologic effect of the pills. The absolute number of additional breast cancer cases will be very small because of low baseline incidence of the disease in young women. Oral contraceptives probably promote growth of the already existing cancer, they are probably promoters not initiators of breast cancer. The available data do not provide a conclusive answer that is needed. CERVICAL CANCER: Numerous factors may influence the development of cervical cancer. The evidence suggests that current and recent oral contraceptive users have an increased risk of cervical cancer which decline after discontinuation of the application of medication. Oral contraceptives might increase the biological vulnerability of the cervix. Cervical cancer develops slowly over a long time period and can be effectivelv prevented by periodic cervical screening. Fortunately, oral contraceptives do not mask abnormal cervical citology. Conclusions regarding invasive cervical cancer and oral contraceptive use are not definitive but if there is any increased risk, it is low. ENDOMETRIAL CANCER: In oral contraceptive users the endometrium is almost under the influence of progestin component which suppresses endometrial mitotic activity and its proliferation. Most epidemiologic studies show that oral contraceptives reduce the risk of endometrial cancer and that this protective effect exists many years after the discontinuation of medication. OVARIAN CANCER: It has been long known that the oral contraceptive use causes protective anovulation and reduces the risk of ovarian cancer. This powerful reduction is the best demonstrated major benefit of oral contraception. This protection is especially observed in nulliparous and seems to persist for many years after the discontinuation of medication.

The presence of antibodies recognizing a peptide derived from the second conserved region of HIV-1 gp120 correlates with non-progressive HIV infection.

The C-terminus of the second conserved region of HIV-1 gp120 represents a functionally important domain, as it encompasses amino acids directly involved in the binding to the CD4 receptor and in post-receptor binding events. Previous studies have suggested that antibodies with specific affinity to a 23 amino acids-long NTM polypeptide, derived from this HIV-1 gp120 domain, may be involved in the control of HIV disease progression. In the current work, we searched for NTM-recognizing antibodies in specific cohorts of HIV-1 infected individuals, including long-term nonprogressors (LTNP) and progressors. For this purpose, we employed a previously defined bioinformatics criterion for design of an NTM peptide mimetic to select an octapeptide, NTMs (FTDNAKTI), which is more suitable for use in a solid-state enzyme-linked immunosorbent assay (ELISA). Our results show that NTMs-reactive antibodies are significantly more prevalent (p < 0.01) in LTNP as compared to progressors and healthy control subjects, indicating their association with non-progressive infection. The presence of antibodies recognizing the second conserved region of the HIV-1 gp120 derived peptide, NTMs, in LTNP sera suggest that these antibodies could be of considerable interest for development of anti-HIV immune-based therapies and vaccines.

[Laparoscopic ovarian biopsy and infertility]. / Laparoskopska biopsija ovarijuma i infertilitet.

In the most developed countries, laparoscopic diagnostics and surgical procedures in the chosen cases still play a very important role and represent the acceptable alternative to the extrauterine fertilization. On the basis of histopathological verification of ovary biopsy cuts taken during the laparoscopy, the optimum conditions are fulfilled for determination of the ovary potentiality enabling the selection of patients for the further proper treatment. 113 patients that, due to the marriage infertility, were examined and treated at the Department of Sterility and infertility of the Obstetrics and Gynecology Clinic, Clinical Center of Nis, with the average age of 31.39 +/- 6.10 and with the average marriage infertility period lasting from 4.11 +/- 2.99 had undergone the surgical laparoscopy. The most frequently used interventions that were performed, disregarding the adnexial findings, were salipongovariolyses in 73 cases (64.60%), then fimbrioplastic in 60 cases (53.10%). Ovary biopsy and histopathological analysis of the cuts taken were performed in 110 patients (89.39%). We got 105 histopathological findings. The most common histopathological findings showed the existence of the primordial folicules in 39.60% of women, with the prevalence in younger ones. (In patients younger than 20--66.67%, while in patients over 40--25%). We found out that the prevailing number of women had the histological findings that spoke on behalf of the potential ovaries in case the infertility lasted shorter. The ovary tissue cuts taken by biopsy that were histopathologically analyzed, showed the significantly higher pregnancy and delivery rate in findings with the primordial folicules present (67.5% of the pregnancy rate 57.5% of the intrauterine pregnancy rate and 47.5% of the delivery rate).