Electrospun Gelatin Scaffolds with Incorporated Antibiotics for Skin Wound Healing.

Recent advances in regenerative medicine provide encouraging strategies to produce artificial skin substitutes. Gelatin scaffolds are successfully used as wound-dressing materials due to their superior properties, such as biocompatibility and the ability to mimic the extracellular matrix of the surrounding environment. In this study, five gelatin combination solutions were prepared and successfully electrospun using an electrospinning technique. After careful screening, the optimal concentration of the most promising combination was selected for further investigation. The obtained scaffolds were crosslinked with 25% glutaraldehyde vapor and characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. The incorporation of antibiotic agents such as ciprofloxacin hydrochloride and gentamicin sulfate into gelatin membranes improved the already existing antibacterial properties of antibiotic-free gelatin scaffolds against Pseudomonas aeruginosa and Staphylococcus aureus. Also, the outcomes from the in vivo model study revealed that skin regeneration was significantly accelerated with gelatin/ciprofloxacin scaffold treatment. Moreover, the gelatin nanofibers were found to strongly promote the neoangiogenic process in the in vivo chick embryo chorioallantoic membrane assay. Finally, the combination of gelatin's extracellular matrix and antibacterial agents in the scaffold suggests its potential for effective wound-healing treatments, emphasizing the importance of gelatin scaffolds in tissue engineering.

Antioxidant Response of Maternal and Fetal Rat Liver to Selenium Nanoparticle Supplementation Compared to Sodium Selenite: Sex Differences between Fetuses.

To compare the effects of organic selenium nanoparticles (SeNPs, Se0) and inorganic sodium selenite (NaSe, Na2SeO3, Se4+) on the antioxidant response in maternal and fetal rat liver, pregnant females were treated with two forms of selenium (Se) at equivalent doses during gestation (0.5 mg SeNPs or 0.5 mg NaSe/kg body weight/day). Structural parameters of the liver of gravid females and their fetuses were examined in a sex-specific manner. The oxidative stress parameters superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione S-transferase (GST), total glutathione (GSH) and sulfhydryl groups (SH) were established. In addition, the Se concentration was determined in the blood, liver, urine and feces of the gravid females and in the liver of the fetuses. The structure of the liver of gravid females remained histologically the same after supplementation with both forms of Se, while the oxidative stress in the liver was significantly lower after the use of SeNPs compared to NaSe. Immaturity of fetal antioxidant defenses and sex specificity were demonstrated. This study provides a detailed insight into the differences in the bioavailability of the nano form of Se compared to sodium selenite in the livers of pregnant females and fetuses.

Sacubitril/valsartan for the treatment of non-obstructive hypertrophic cardiomyopathy: An open label randomized controlled trial (SILICOFCM).

AIM: Sacubitril/valsartan treatment reduces mortality and hospitalizations in heart failure with reduced ejection fraction but has limited application in hypertrophic cardiomyopathy (HCM). The aim of this study was to evaluate the effect of sacubitril/valsartan on peak oxygen consumption (VO2) in patients with non-obstructive HCM. METHODS AND RESULTS: This is a phase II, randomized, open-label multicentre study that enrolled adult patients with symptomatic non-obstructive HCM (New York Heart Association class I-III) who were randomly assigned (2:1) to receive sacubitril/valsartan (target dose 97/103 mg) or control for 16 weeks. The primary endpoint was a change in peak VO2. Secondary endpoints included echocardiographic measures of cardiac structure and function, natriuretic peptides and other cardiac biomarkers, and Minnesota Living with Heart Failure quality of life. Between May 2018 and October 2021, 354 patients were screened for eligibility, 115 patients (mean age 58 years, 37% female) met the study inclusion criteria and were randomly assigned to sacubitril/valsartan (n = 79) or control (n = 36). At 16 weeks, there was no significant change in peak VO2 from baseline in the sacubitril/valsartan (15.3 [4.3] vs. 15.9 [4.3] ml/kg/min, p = 0.13) or control group (p = 0.47). No clinically significant changes were found in blood pressure, cardiac structure and function, plasma biomarkers, or quality of life. CONCLUSION: In patients with HCM, a 16-week treatment with sacubitril/valsartan was well tolerated but had no effect on exercise capacity, cardiac structure, or function.

A Review of Recent Developments in Biopolymer Nano-Based Drug Delivery Systems with Antioxidative Properties: Insights into the Last Five Years.

In recent years, biopolymer-based nano-drug delivery systems with antioxidative properties have gained significant attention in the field of pharmaceutical research. These systems offer promising strategies for targeted and controlled drug delivery while also providing antioxidant effects that can mitigate oxidative stress-related diseases. Generally, the healthcare landscape is constantly evolving, necessitating the continual development of innovative therapeutic approaches and drug delivery systems (DDSs). DDSs play a pivotal role in enhancing treatment efficacy, minimizing adverse effects, and optimizing patient compliance. Among these, nanotechnology-driven delivery approaches have garnered significant attention due to their unique properties, such as improved solubility, controlled release, and targeted delivery. Nanomaterials, including nanoparticles, nanocapsules, nanotubes, etc., offer versatile platforms for drug delivery and tissue engineering applications. Additionally, biopolymer-based DDSs hold immense promise, leveraging natural or synthetic biopolymers to encapsulate drugs and enable targeted and controlled release. These systems offer numerous advantages, including biocompatibility, biodegradability, and low immunogenicity. The utilization of polysaccharides, polynucleotides, proteins, and polyesters as biopolymer matrices further enhances the versatility and applicability of DDSs. Moreover, substances with antioxidative properties have emerged as key players in combating oxidative stress-related diseases, offering protection against cellular damage and chronic illnesses. The development of biopolymer-based nanoformulations with antioxidative properties represents a burgeoning research area, with a substantial increase in publications in recent years. This review provides a comprehensive overview of the recent developments within this area over the past five years. It discusses various biopolymer materials, fabrication techniques, stabilizers, factors influencing degradation, and drug release. Additionally, it highlights emerging trends, challenges, and prospects in this rapidly evolving field.

Application of parallel artificial membrane permeability assay technique and chemometric modeling for blood-brain barrier permeability prediction of protein kinase inhibitors.

Aim: This study aims to investigate the passive diffusion of protein kinase inhibitors through the blood-brain barrier (BBB) and to develop a model for their permeability prediction. Materials & methods: We used the parallel artificial membrane permeability assay to obtain logPe values of each of 34 compounds and calculated descriptors for these structures to perform quantitative structure-property relationship modeling, creating different regression models. Results: The logPe values have been calculated for all 34 compounds. Support vector machine regression was considered the most reliable, and CATS2D_09_DA, CATS2D_04_AA, B04[N-S] and F07[C-N] descriptors were identified as the most influential to passive BBB permeability. Conclusion: The quantitative structure-property relationship-support vector machine regression model that has been generated can serve as an efficient method for preliminary screening of BBB permeability of new analogs.

[Box: see text].

Schiff bases and their metal complexes to target and overcome (multidrug) resistance in cancer.

Overcoming multidrug resistance (MDR) is one of the major challenges in cancer therapy. In this respect, Schiff base-related compounds (bearing a R1R2CNR3 bond) gained high interest during the past decades. Schiff bases are considered privileged ligands for various reasons, including the easiness of their preparation and the possibility to form complexes with almost all transition metal ions. Schiff bases and their metal complexes exhibit many types of biological activities and are used for the treatment and diagnosis of various diseases. Until now, 13 Schiff bases have been investigated in clinical trials for cancer treatment and hypoxia imaging. This review represents the first collection of Schiff bases and their complexes which demonstrated MDR-reversal activity. The areas of drug resistance covered in this article involve: 1) Modulation of ABC transporter function, 2) Targeting lysosomal ABCB1 overexpression, 3) Circumvention of ABC transporter-mediated drug efflux by alternative routes of drug uptake, 4) Selective activity against MDR cancer models (collateral sensitivity), 5) Targeting GSH-detoxifying systems, 6) Overcoming apoptosis resistance by inducing necrosis and paraptosis, 7) Reactivation of mutated p53, 8) Restoration of sensitivity to DNA-damaging anticancer therapy, and 9) Overcoming drug resistance through modulation of the immune system. Through this approach, we would like to draw attention to Schiff bases and their metal complexes representing highly interesting anticancer drug candidates with the ability to overcome MDR.

Biological Activity of 6,7-Dehydroxyroyleanone and Derivatives Obtained from Plectranthus aliciae (Codd) A.J.Paton.

The Plectranthus genus (Lamiaceae) is known to be rich in abietane diterpenes. The bioactive 6,7-dehydroxyroyleanone (DHR, 1) was previously isolated from Plectranthus madagascariensis var. madagascariensis and var. aliciae. This study aimed to explore the occurrence of DHR, 1, in P. aliciae and the potential bioactivities of new semisynthetic derivatives from DHR, 1. Several extraction methods were evaluated, and the hydrodistillation, using a Clevenger apparatus, afforded the highest yield (77.8 mg/g of 1 in the essential oil). Three new acyl derivatives (2-4) were successfully prepared from 1 (yields of 86-95%). Compounds 1-4 showed antioxidant activity, antibacterial effects, potent cytotoxic activity against several cell lines, and enhanced anti-inflammatory activity that surpassed dexamethasone (positive control). These findings encourage further exploration of derivatives 2-4 for potential mechanisms of antitumoral, antioxidant, and anti-inflammatory capabilities, studying both safety and efficacy.

AI-Driven Optimization of PCL/PEG Electrospun Scaffolds for Enhanced In Vivo Wound Healing.

Here, an artificial intelligence (AI)-based approach was employed to optimize the production of electrospun scaffolds for in vivo wound healing applications. By combining polycaprolactone (PCL) and poly(ethylene glycol) (PEG) in various concentration ratios, dissolved in chloroform (CHCl3) and dimethylformamide (DMF), 125 different polymer combinations were created. From these polymer combinations, electrospun nanofiber meshes were produced and characterized structurally and mechanically via microscopic techniques, including chemical composition and fiber diameter determination. Subsequently, these data were used to train a neural network, creating an AI model to predict the optimal scaffold production solution. Guided by the predictions and experimental outcomes of the AI model, the most promising scaffold for further in vitro analyses was identified. Moreover, we enriched this selected polymer combination by incorporating antibiotics, aiming to develop electrospun nanofiber scaffolds tailored for in vivo wound healing applications. Our study underscores three noteworthy conclusions: (i) the application of AI is pivotal in the fields of material and biomedical sciences, (ii) our methodology provides an effective blueprint for the initial screening of biomedical materials, and (iii) electrospun PCL/PEG antibiotic-bearing scaffolds exhibit outstanding results in promoting neoangiogenesis and facilitating in vivo wound treatment.

Modeling 5-FU-Induced Chemotherapy Selection of a Drug-Resistant Cancer Stem Cell Subpopulation.

(1) Background: Cancer stem cells (CSCs) are a subpopulation of cells in a tumor that can self-regenerate and produce different types of cells with the ability to initiate tumor growth and dissemination. Chemotherapy resistance, caused by numerous mechanisms by which tumor tissue manages to overcome the effects of drugs, remains the main problem in cancer treatment. The identification of markers on the cell surface specific to CSCs is important for understanding this phenomenon. (2) Methods: The expression of markers CD24, CD44, ALDH1, and ABCG2 was analyzed on the surface of CSCs in two cancer cell lines, MDA-MB-231 and HCT-116, after treatment with 5-fluorouracil (5-FU) using flow cytometry analysis. A machine learning model (ML)-genetic algorithm (GA) was used for the in silico simulation of drug resistance. (3) Results: As evaluated through the use of flow cytometry, the percentage of CD24-CD44+ MDA-MB-231 and CD44, ALDH1 and ABCG2 HCT-116 in a group treated with 5-FU was significantly increased compared to untreated cells. The CSC population was enriched after treatment with chemotherapy, suggesting that these cells have enhanced drug resistance mechanisms. (4) Conclusions: Each individual GA prediction model achieved high accuracy in estimating the expression rate of CSC markers on cancer cells treated with 5-FU. Artificial intelligence can be used as a powerful tool for predicting drug resistance.

Acute Toxicity Assessment of Orally Administered Microplastic Particles in Adult Male Wistar Rats.

While the effects of chronic exposure to microplastic particles (MPs) are extensively studied, the outcomes of a single treatment have received relatively less attention. To investigate MPs' potential acute toxicity, including their impact on general health status (victual consumption, sensorimotor deficits, and clinical toxicity signs) and serum biochemical parameters (markers of organ/tissue function and oxidative stress indicators), we administered thoroughly characterized MPs (1.4, 35, or 125 mg/kg), generated from polyethylene terephthalate (PET) bottles, to adult male Wistar rats via oral gavage. The MPs' short-term effects were assessed with well-established tests and methods. The results point to the absence of sensorimotor deficits and clinical toxicity signs, while levels of markers of liver, heart, and kidney function were altered in all MP groups. Decreased victual consumption and increased levels of oxidative stress indicators were evident following treatment with the two higher MP doses. Presented data indicate that examined MPs are able to initiate the development of local changes in tissues and organs within a short time frame, potentially leading to their damage and dysfunction. This study may increase the awareness of the detrimental effects of plastic contamination, as even a single exposure to MPs may provoke adverse health outcomes.

Software that combines deep learning, 3D reconstruction and CFD to analyze the state of carotid arteries from ultrasound imaging.

BACKGROUND: Ultrasound is one of the non-invasive techniques that are used in clinical diagnostics of carotid artery disease. OBJECTIVE: This paper presents software methodology that can be used in combination with this imaging technique to provide additional information about the state of patient-specific artery. METHODS: Overall three modules are combined within the proposed methodology. A clinical dataset is used within the deep learning module to extract the contours of the carotid artery. This data is then used within the second module to perform the three-dimensional reconstruction of the geometry of the carotid bifurcation and ultimately this geometry is used within the third module, where the hemodynamic analysis is performed. The obtained distributions of hemodynamic quantities enable a more detailed analysis of the blood flow and state of the arterial wall and could be useful to predict further progress of present abnormalities in the carotid bifurcation. RESULTS: The performance of the deep learning module was demonstrated through the high values of relevant common classification metric parameters. Also, the accuracy of the proposed methodology was shown through the validation of results for the reconstructed parameters against the clinically measured values. CONCLUSION: The presented methodology could be used in combination with standard clinical ultrasound examination to quickly provide additional quantitative and qualitative information about the state of the patient's carotid bifurcation and thus ensure a treatment that is more adapted to the specific patient.

Resveratrol/Selenium Nanocomposite with Antioxidative and Antibacterial Properties.

In this work, we synthesized a new composite material comprised of previously formulated resveratrol nanobelt-like particles (ResNPs) and selenium nanoparticles (SeNPs), namely ResSeNPs. Characterization was provided by FESEM and optical microscopy, as well as by UV-Vis and FTIR spectroscopy, the last showing hydrogen bonds between ResNPs and SeNPs. DPPH, TBA, and FRAP assays showed excellent antioxidative abilities with ResNPs and SeNPs contributing mainly to lipid peroxidation inhibition and reducing/scavenging activity, respectively. The antibacterial effect against common medicinal implant colonizers pointed to notably higher activity against Staphylococcus isolates (minimal inhibitory concentrations 0.75-1.5%) compared to tested gram-negative species (Escherichia coli and Pseudomonas aeruginosa). Antibiofilm activity against S. aureus, S. epidermidis, and P. aeruginosa determined in a crystal violet assay was promising (up to 69%), but monitoring of selected biofilm-related gene expression (pelA and algD) indicated the necessity of the involvement of a larger number of genes in the analysis in order to further establish the underlying mechanism. Although biocompatibility screening showed some cytotoxicity and genotoxicity in MTT and alkaline comet assays, respectively, it is important to note that active antioxidative and antibacterial/antibiofilm concentrations were non-cytotoxic and non-genotoxic in normal MRC-5 cells. These results encourage further composite improvements and investigation in order to adapt it for specific biomedical purposes.

Evaluation of novel dendrimer-gold complex nanoparticles for theranostic application in oncology.

Aim: Despite some successful examples of therapeutic nanoparticles reaching clinical stages, there is still a significant need for novel formulations in order to improve the selectivity and efficacy of cancer treatment. Methods: The authors developed two novel dendrimer-gold (Au) complex-based nanoparticles using two different synthesis routes: complexation method (formulation A) and precipitation method (formulation B). Using a biomimetic cancer-on-a-chip model, the authors evaluated the possible cytotoxicity and internalization by colorectal cancer cells of dendrimer-Au complex-based nanoparticles. Results: The results showed promising capabilities of these nanoparticles for selectively targeting cancer cells and delivering drugs, particularly for the formulation A nanoparticles. Conclusion: This work highlights the potential of dendrimer-Au complex-based nanoparticles as a new strategy to improve the targeting of anticancer drugs.

Multiple regression analysis for competitive performance assessment of professional soccer players.

BACKGROUND: Being in peak physical condition and having specific motor abilities are necessity for every top-level soccer player in order to achieve success in competition. In order to correctly assess soccer players' performance, this research uses laboratory and field measurements, as well as results of competitive performance obtained by direct software measurements of players' movement during the actual soccer game. OBJECTIVE: The main goal of this research is to give insight into the key abilities that soccer players need to have in order to perform in competitive tournaments. Besides training adjustments, this research also gives insight into what variables need to be tracked in order to accurately assess the efficiency and functionality of the players. METHODS: The collected data need to be analyzed using descriptive statistics. Collected data is also used as input for multiple regression models that can predict certain key measurements: total distance covered, percent of effective movements and high index of effective performance movements. RESULTS: Most of the calculated regression models have high predictability level with statistically significant variables. CONCLUSION: Based on the results of regression analysis it can be deduced that motor abilities are important factor in measuring soccer player's competitive performance and team's success in the match.

Quinoline-based thiazolyl-hydrazones target cancer cells through autophagy inhibition.

Heterocyclic pharmacophores such as thiazole and quinoline rings have a significant role in medicinal chemistry. They are considered privileged structures since they constitute several Food and Drug Administration (FDA)-approved drugs for cancer treatment. Herein, we report the synthesis, in silico evaluation of the ADMET profiles, and in vitro investigation of the anticancer activity of a series of novel thiazolyl-hydrazones based on the 8-quinoline (1a-c), 2-quinoline (2a-c), and 8-hydroxy-2-quinolyl moiety (3a-c). The panel of several human cancer cell lines and the nontumorigenic human embryonic kidney cell line HEK-293 were used to evaluate the compound-mediated in vitro anticancer activities, leading to [2-(2-(quinolyl-8-ol-2-ylmethylene)hydrazinyl)]-4-(4-methoxyphenyl)-1,3-thiazole (3c) as the most promising compound. The study revealed that 3c blocks the cell-cycle progression of a human colon cancer cell line (HCT-116) in the S phase and induces DNA double-strand breaks. Also, our findings demonstrate that 3c accumulates in lysosomes, ultimately leading to the cell death of the hepatocellular carcinoma cell line (Hep-G2) and HCT-116 cells, by the mechanism of autophagy inhibition.

Analysis of modified surface topographies of titanium-based hip implants using finite element method.

BACKGROUND: In order to ensure the proper function of the cementless hip implant, the connection between the femoral bone and the implant has to be as strong as possible. According to experimental studies, implants with a rough surface reduce micro-movements between femoral bone and implant, which helps form a stronger connection between them. OBJECTIVE: The goal of this study was to analyze how half-cylinder surface topographies of different diameter values affect shear stress values and their distribution on the surface of the hip implant and trabecular femoral bone. METHODS: Nine models with different half-cylinder diameter values (200 µm, 400 µm, and 500 µm) and distances between half-cylinders were created for the analysis using the finite element method. Each model consisted of three layers: implant, trabecular, and cortical femoral bone. RESULTS: For all three diameter values, the highest shear stress value, for the implant layer, was located after the first half-cylinder on the side where force was defined. For the trabecular bone, the first half-cylinder was under lower amounts of shear stress. CONCLUSION: If we only consider shear stress values, we can say that models with 400 µm and 500 µm diameter values are a better choice than models with 100 µm diameter values.

An Effective, Green Synthesis Procedure for Obtaining Coumarin-Hydroxybenzohydrazide Derivatives and Assessment of Their Antioxidant Activity and Redox Status.

In this study, green synthesis of two derivatives of coumarin-hydroxybenzohydrazide, (E)-2,4-dioxo-3-(1-(2-(2,3,4-trihydroxybenzoyl)hydrazyl)ethylidene)-chroman-7-yl acetate (C-HB1), and (E)-2,4-dioxo-3-(1-(2-(3,4,5-trihydroxybenzoyl)hydrazyl)ethylidene)chroman-7-yl acetate (C-HB2) is reported. Using vinegar and ethanol as a catalyst and solvent, the reactions were carried out between 3-acetyl-4-hydroxy-coumarin acetate and corresponding trihydroxybenzoyl hydrazide. The antioxidant potential of these compounds was investigated using the DPPH and ABTS assays, as well as the FRAP test. The obtained results reveal that even at very low concentrations, these compounds show excellent radical scavenging potential. The IC50 values for C-HB1 and C-HB2 in relation to the DPPH radical are 6.4 and 2.5 µM, respectively, while they are 4.5 and 2.0 µM in relation to the ABTS radical. These compounds have antioxidant activity that is comparable to well-known antioxidants such as gallic acid, NDGA, and trolox. These results are in good correlation with theoretical parameters describing these reactions. Moreover, it was found that inhibition of DPPH● follows HAT, while inactivation of ABTS+● follows SET-PT and HAT mechanisms. Additionally, coumarin-hydroxybenzohydrazide derivatives induced moderate cytotoxic activity and show significant potential to modulate redox status in HCT-116 colorectal cancer cells. The cytotoxicity was achieved via their prooxidative activity and ability to induce oxidative stress in cancer cells by increasing O2˙- concentrations, indicated by increased MDA and GSH levels. Thus, ROS manipulation can be a potential target for cancer therapies by coumarins, as cancer cells possess an altered redox balance in comparison to normal cells. According to the ADMET analysis, the compounds investigated show good pharmacokinetic and toxicological profiles similar to vitamin C and gallic acid, which makes them good candidates for application in various fields of industry and medicine.

Correction: Qamar et al. Treatment of Peripheral Artery Disease Using Injectable Biomaterials and Drug-Coated Balloons: Safety and Efficacy Perspective. Pharmaceutics 2023, 15, 1813.

There was an error in the original publication [...].

Fractional Flow Reserve-Based Patient Risk Classification.

Cardiovascular diseases (CVDs) are a leading cause of death. If not treated in a timely manner, cardiovascular diseases can cause a plethora of major life complications that can include disability and a loss of the ability to work. Globally, acute myocardial infarction (AMI) is responsible for about 3 million deaths a year. The development of strategies for prevention, but also the early detection of cardiovascular risks, is of great importance. The fractional flow reserve (FFR) is a measurement used for an assessment of the severity of coronary artery stenosis. The goal of this research was to develop a technique that can be used for patient fractional flow reserve evaluation, as well as for the assessment of the risk of death via gathered demographic and clinical data. A classification ensemble model was built using the random forest machine learning algorithm for the purposes of risk prediction. Referent patient classes were identified by the observed fractional flow reserve value, where patients with an FFR higher than 0.8 were viewed as low risk, while those with an FFR lower than 0.8 were identified as high risk. The final classification ensemble achieved a 76.21% value of estimated prediction accuracy, thus achieving a mean prediction accuracy of 74.1%, 77.3%, 78.1% and 83.6% over the models tested with 5%, 10%, 15% and 20% of the test samples, respectively. Along with the machine learning approach, a numerical approach was implemented through a 3D reconstruction of the coronary arteries for the purposes of stenosis monitoring. Even with a small number of available data points, the proposed methodology achieved satisfying results. However, these results can be improved in the future through the introduction of additional data, which will, in turn, allow for the utilization of different machine learning algorithms.

Its all about IFN-λ4: Protective role of IFNL4 polymorphism against COVID-19-related pneumonia in females.

Despite the pivotal role of IFN-λs in the innate immune response, the data on its genetic polymorphism in relation to COVID-19 severity are scarce and contradictory. In the present study, we aimed to determine if the presence of the most frequent functional single nucleotide polymorphisms (SNPs) of the two most important IFN-λs coding genes, namely IFNL3 and IFNL4, alters the likelihood of SARS-CoV-2-infected patients to develop more severe form of the disease. This observational cohort study involved 178 COVID-19 patients hospitalized at the University Clinical Centre Kragujevac, Serbia. Patients' demographics, clinical characteristics, and laboratory parameters were collected at admission. COVID-19 signs and symptoms were assessed during the hospital stay, with the worst condition determining the disease severity. Genotyping for IFNL3 (rs12980275 and rs8099917) and IFNL4 (rs12979860 and rs368234815) SNPs was conducted using TaqMan assays. Our study revealed carriers of IFNL3 and IFNL4 minor alleles to be less likely to progress from mild to moderate COVID-19, that is, to develop COVID-19-related pneumonia. After adjustment for other factors of influence, such as age, sex, and comorbidities, the likelihood of pneumonia development remained significantly associated with IFNL4 polymorphism (odds ratios [ORs] [95% confidence interval (95% CI)]: 0.233 [0.071; 0.761]). When the patients were stratified according to sex, the protective role of IFNL4 minor alleles, controlled for the effect of comorbidities, remained significant only in females (OR [95% CI]: 0.035 [0.003; 0.408]). Our results strongly suggest that IFNL4 rs12979860 and rs368234815 polymorphisms independently predict the risk of COVID-19-related pneumonia development in females.