Journal of APPLIED BIOMEDICINE (2024)

Background: Despite the many benefits that follow antiretroviral therapy (ART) initiation, its chronic use contributes to the early aging of people living with HIV/AIDS (PLWHA). The aim of this cross-sectional study was to trace the prevalence of and investigate possible renal, bone and metabolic changes, as well as cardiovascular risk in 94 asymptomatic PLWHA, relating them to the duration of ART use. Methods: Four groups were evaluated according to ART use: G1 (n = 21), ART-naïve individuals; G2 (n = 17), <2 years; G3 (n = 40), 2-10 years; and G4 (n = 16) on ART for more than 10 years. Results: Our results showed a high prevalence of dyslipidemic individuals (64%), especially in those under ART. Lower creatine phosphokinase levels were observed in G1 as compared to the others (p < 0.05). Regarding the Framingham score, 12.1% of PLWHA showed moderate and high risk, and the highest proportion (38.5%) occurred in G4 (p = 0.003). A decrease in glomerular filtration rates occurred in 20% of patients, which was also more significant in G3 and G4 (p = 0.007). High prevalences of osteopenia and osteoporosis (53.2%) were found, especially in G1 and G4; however, G1 showed the lowest means for alkaline phosphatases (AP, p = 0.04 and BAP, p = 0.005) and osteocalcin (p = 0.005), in addition to higher vitamin-D concentrations (p = 0.04). Conclusions: Our study showed the possible contributory role of ART in these changes, which leads us to reflect on the need for specific conducts and patient care, pointing out the importance of individualized care in an attempt to increase life expectancy.

Background: The core motive of pharmacovigilance is the detection and prevention of adverse drug reactions (ADRs), to improve the risk-benefit balance of the drug. However, the causality assessment of ADRs remains a major challenge among clinicians, and none of the available tools of causality assessment used for assessing ADRs have been universally accepted. Objective: To provide an up-to-date overview of the different causality assessment tools. Methods: We conducted electronic searches in MEDLINE, EMBASE, and the Cochrane database. The eligibility of each tool was screened by three reviewers. Each eligible tool was then scrutinized for its domains (the reported specific set of questions/areas used for calculating the likelihood of cause-and-effect relation of an ADR) to discover the most comprehensive tool. Finally, we subjectively assessed the tool's ease-of-use in a Canadian, Indian, Hungarian, and Brazilian clinical context. Results: Twenty-one eligible causality assessment tools were retrieved. Naranjo's tool and De Boer's tool appeared the most comprehensive among all the tools, covering 10 domains each. Regarding "ease-of-use" in a clinical setting, we judged that many tools were hard to implement in a clinical context because of their complexity and/or lengthiness. Naranjo's tool, Jones's tool, Danan and Benichou's tool, and Hsu and Stoll's tool appeared to be the easiest to implement into various clinical contexts. Conclusion: Among the many tools identified, 1981 Naranjo's scale remains the most comprehensive and easy to use for performing causality assessment of ADRs. Upcoming analysis should compare the performance of each ADR tool in clinical settings.

Background: The ADIPOQ gene encodes a fat-derived protein hormone with a preponderant role in the homeostasis of glucose and fatty acids. However, previous association studies between ADIPOQ genetic variants and metabolic disorders have shown controversial results. In this study, we evaluated the effect of the ADIPOQ-rs2241766 polymorphism on diverse biochemical parameters (i.e., insulin resistance, atherogenic index, overweight and obesity) in an adolescent population from Mexico. Methods: A cross-sectional study with convenience sampling was carried out in 356 adolescents from Northern Mexico. They were classified by sex and BMI-z score. The biochemical parameters were measured from blood samples using conventional methods. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: In low and normal weight groups, GG carriers had a significantly higher cholesterol level (P ≤ 0.05) than TG and TT carriers. However, there was no association between ADIPOQ-rs2241766 polymorphism and atherogenic index, overweight, or obesity. Conclusions: Our findings suggest that the cholesterol levels are under the influence of the ADIPOQ-rs2241766 polymorphism in Mexican adolescents and may explain how ADIPOQ variants increase the risk of developing metabolic disorders. Nevertheless, further studies are required to rule out the influence of other genetic and non-genetic factors.

Skin cancer has high rates of mortality and therapeutic failure. In this study, to develop a multi-agent strategy for skin cancer management, the selective cytotoxicity of several alkaloid fractions and pure alkaloids isolated from Amaryllidaceae species was evaluated in melanoma cells. In addition, UVB-stimulated keratinocytes (HaCaT) were exposed to seven alkaloid fractions characterized by GC-MS, and the production of intracellular reactive oxygen species (ROS) and IL-6, were measured to evaluate their photoprotection effects. The Eucharis caucana (bulb) alkaloid fraction (20 μg/ml) had a clear effect on the viability of melanoma cells, reducing it by 45.7% without affecting healthy keratinocytes. This alkaloid fraction and tazettine (both at 2.5 μg/ml) suppressed UVB-induced ROS production by 31.6% and 29.4%, respectively. The highest anti-inflammatory potential was shown by the Zephyranthes carinata (bulb) alkaloid fraction (10 μg/ml), which reduced IL-6 production by 90.8%. According to the chemometric analysis, lycoramine and tazettine had a photoprotective effect on the UVB-exposed HaCaT cells, attenuating the production of ROS and IL-6. These results suggest that Amaryllidaceae alkaloids have photoprotective and therapeutic potential in skin cancer management, especially at low concentrations.

Carvacrol presents action in Salmonella Typhimurium biofilms, however the antibiofilm mechanism of this compound has not been fully established yet. In the present study, the aim was to evaluate protein profile changes in S. Typhimurium biofilm treated with carvacrol. Proteomic analysis of treated versus untreated biofilm showed several changes in proteins involved with S. Typhimurium biofilm and antioxidant activity. The proteins DsbA (thiol: disulfide interchange protein DsbA), LuxS (S-ribosylhom*ocysteine lyase), DksA (RNA polymerase binding transcription factor DksA), and SODs (superoxide dismutases) A, B and C had their synthesis decreased after treatment with carvacrol. These proteins play a key role in S. Typhimurium biofilm formation, demonstrating the dynamic antibiofilm action of carvacrol. The differentially expressed proteins identified provide possible action targets for future studies in order to gain more insight into the mechanism of action of carvacrol on S. Typhimurium biofilm.

Dyslipidemias are lipid metabolism alterations that cause increased levels of serum lipoprotein, cholesterol, and triglycerides. These alterations are associated with a higher incidence of cardiovascular diseases and are a risk factor for atherosclerosis development. This study aimed to evaluate the effect of Rosmarinus officinalis essential oil (EORO, 100 mg/kg) and its nanoemulsion (NEORO, 500 µg/kg) on Triton and coconut saturated-fat-induced (CSF) dyslipidemias using Wistar rats. The phytochemical evaluation of EORO performed by gas chromatography-mass spectroscopy (GC-MS) revealed 1,8-cineole (33.70%), camphor (27.68%), limonene (21.99%), and α-pinene (8.13%) as its major compounds. Triton-induced dyslipidemia significantly increased total cholesterol, LDL, and triglycerides levels. On the other hand, the groups treated with EORO and NEORO had significantly reduced total cholesterol, LDL, and triglycerides compared to the group treated only with Triton. Similar results were observed on the positive control treated with simvastatin. Dyslipidemia induced with coconut saturated-fat (CSF) caused abdominal fat gain, hypercholesterolemia, hypertriglyceridemia, increased LDL levels, and atherogenesis in the aorta. In contrast, the groups treated with EORO, NEORO, and simvastatin had significantly reduced hypercholesterolemia and hypertriglyceridemia, reduced abdominal fat gain, and absence of atherogenesis in the vascular endothelium. Overall, in the Triton-induced dyslipidemia model, EORO treatment had superior values than NEORO's (and simvastatin), although the differences were not too high, while in the CSF model, the values were mixed. In this manner, our results show an anti-dyslipidemic and anti-atherogenic activity effect by EORO and NEORO.

Oplopanax elatus (Nakai) Nakai has a long history of use as an ethnomedicine by the people living in eastern Asia. However, its bioactive constituents and cancer chemopreventive mechanisms are largely unknown. The aim of this study was to prepare O. elatus extracts, fractions, and single compounds and to investigate the herb's antiproliferative effects on colon cancer cells and the involved mechanisms of action. Two polyyne compounds were isolated from O. elatus, falcarindiol and oplopandiol. Based on our HPLC analysis, falcarindiol and oplopandiol are major constituents in the dichloromethane (CH2Cl2) fraction. For the HCT-116 cell line, the dichloromethane fraction showed significant effects. Furthermore, the IC50 for falcarindiol and oplopandiol was 1.7 µM and 15.5 µM, respectively. In the mechanistic study, after treatment with 5 µg/ml for 48 h, dichloromethane fraction induced cancer cell apoptosis by 36.5% (p < 0.01% vs. control of 3.9%). Under the same treatment condition, dichloromethane fraction caused cell cycle arrest at the G2/M phase by 32.6% (p < 0.01% vs. control of 23.4%), supported by upregulation of key cell cycle regulator cyclin A to 21.6% (p < 0.01% vs. control of 8.6%). Similar trends were observed by using cell line HT-29. Data from this study filled the gap between phytochemical components and the cancer chemoprevention of O. elatus. The dichloromethane fraction is a bioactive fraction, and falcarindiol is identified as an active constituent. The mechanisms involved in cancer chemoprevention by O. elatus were apoptosis induction and G2/M cell cycle arrest mediated by a key cell cycle regulator cyclin A.

This study aimed to analyze the effect of fall risk-increasing drugs (FRIDs) and drug-related factors relative to falls through clinical pharmacy service in hospitalized patients, focusing on the relevance of clinical pharmacist evaluation in the context of physician assessment. A prospective study of inpatient falls was conducted in 2017 retrieving data from 4 hospitals in South Bohemia, Czech Republic. An online database was developed to collect patient and fall-related data, and fall evaluation records. Healthcare professionals classified the overall effect of drugs on falls using Likert scale. Univariate and multivariate correlations were performed with a significance level of p < 0.05. Out of the total 280 falls (mean age of patients 77.0 years), a mean of 2.8 diagnoses with fall-related risk, 8.8 drugs, and 4.1 FRIDs per fall were identified. Incidence of falls decreased quarterly (p < 0.001). Use of FRIDs were positively associated with increasing age (p = 0.007). Clinical pharmacists were more likely to identify pharmacotherapy as the relevant fall-related risk, compared to physicians evaluation (p < 0.001). An increasing total number of prescribed drugs as well as higher number of FRIDs increased the suspicion in both professionals in the context of drug-related causes of falls.

This study investigated the effect of the topical treatment with meloxicam-loaded nanocapsules (M-NC) on symptoms, inflammatory response and oxidative parameters in an atopic dermatitis (AD) model in BALB/c mice. 2,4-Dinitrochlorobenzene (DNCB) was applied to the dorsal skin on days 1-3 for sensitization. Mice were challenged with DNCB on the ear (on days 14-29) and dorsal skin (on days 14, 17, 20, 23, 26, and 29). Treatments with blank nanocapsules (B-NC), free meloxicam (M-F) or M-NC were applied to the backs of the mice from days 14 to 29. On the day 30, skin severity scores and scratching behaviour were determined. After that, ears and dorsal skin were removed for determination of inflammatory parameters (edema and myeloperoxidase (MPO) activity) and oxidative parameters (thiobarbituric acid reactive species (TBARS) and non-protein thiol (NPSH) levels), respectively. DNCB increased the severity of skin lesions, scratching behaviour, edema and MPO activity of ears and dorsal skin TBARS levels. M-NC reversed skin severity scores, scratching behaviour and inflammatory response induced by DNCB. B-NC and M-F did not have effect in this model. In summary, meloxicam carried by polymeric nanocapsules reversed inflammatory response and ameliorated symptoms in an AD model.

Background: Endoplasmic reticulum (ER) stress has been shown to play an important role in osteoarthritis (OA). Objective: This study was aimed at assessing the relationship of endoplasmic reticulum (ER) stress-related glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein hom*ologous protein (CHOP) concentrations in the serum/synovial fluid (SF) with disease severity of primary knee osteoarthritis (pkOA). Methods: Patients with pkOA together with healthy individuals were consecutively recruited from our hospital. The levels of GRP78 and CHOP in serum / SF were detected using enzyme-linked immunosorbent assay. The levels of IL-6 and MMP-3 were also examined. Radiographic progression of pkOA was evaluated based on Kellgren-Lawrence (K-L) grades. Receiver Operating Characteristic (ROC) curves were used to assess the diagnostic value of GRP78/CHOP levels with regard to K-L grades. The assessment of clinical severity was conducted using the visual analogue scale (VAS), Oxford knee score (OKS), and Lequesne algofunctional index (LAI). Results: A total of 140 pkOA patients and 140 healthy individuals were included. Serum GRP78 and CHOP levels in pkOA patients were not significantly different from those in healthy individuals. The SF GRP78 and CHOP levels in healthy controls were not detected due to ethical reasons. Compared to those with K-L grade 2 and 3, the pkOA patients with K-L grade 4 had higher GRP78 and CHOP levels in the SF with statistical significance. In addition, the pkOA patients with K-L grade 3 exhibited drastically upregulated GRP78 and CHOP concentrations in the SF compared to those with K-L grade 2. Positive correlations of GRP78 and CHOP levels with K-L grades, IL-6, and MMP-3 levels in the SF were observed. ROC curve analysis indicated that both GRP78 and CHOP levels may act as decent indicators with regard to OA. GRP78 and CHOP concentrations in the SF were positively correlated with VAS/LAI score and negatively associated with OKS score. Conclusion: The study indicated that GRP78 and CHOP levels in the SF but not the serum were positively correlated with disease severity of pkOA.

Periodontal regenerative techniques are performed to accomplish the restitution of soft and hard teeth-supporting tissues that have been lost due to trauma or inflammatory disease. Periodontal membranes are used for these techniques to provide support and a framework for cell growth and tissue regeneration. They act as a temporary and selective barrier to cell proliferation. Easy clinical handling, biomechanical specifications, high biocompatibility, cell-occlusivity, and satisfactory bioresorption rate are essential properties a membrane needs to be effective. The creation and maintenance of a secluded space is also a fundamental rule in periodontal regenerative techniques. The use of barrier membranes in the field of restorative dentistry has progressed toward the use of minimally invasive approaches optimizing wound closure and limiting patient morbidity. This review intends to provide an overview of the major cellular events in the surgical wound and membrane surface. It was also performed to assess, from literature data, the pertinence of using non-resorbable and resorbable membranes for this regenerative purpose. Special attention will be given to collagen membranes.

We have extracted and characterized Phasa fish (Setipinna phasa) oil for the first time to evaluate the anti-obesity and related anti-inflammatory effects on obese mice. Inbred male albino BALB/c mice were segregated into three categories: control (C), Obese control group (OC), and Phasa fish oil treated group (TX). To establish the potentiality of Setipinna phasa oil for its anti-obesity and anti-inflammatory properties, it was extracted and characterized using GC-MS method. To evaluate the anti-obesity effect, different parameters were considered, such as body weight, lipid composition, obesity, and obesity associated inflammation. The physicochemical characteristics of Phasa fish oil revealed that the oil quality was good because acid value, peroxide value, p-anisidine value, Totox value, refractive index, and saponification value were within the standard value range. The GC-MS study explored the presence of fatty acids beneficial to health such as Hexadec-9-enoic acid; Octadec-11-enoic acid; EPA, DHA, Methyl Linolenate, etc. The application of Setipinna phasa oil on the treated mice group acutely lowered body weight and serum lipid profile compared to the obese group. In connection with this, leptin, FAS, and pro-inflammatory cytokines TNF-α genes expression were downregulated in the treated group compared to the obese group. The Phasa oil treated group had an elevated expression of PPAR-α, adiponectin, LPL gene, and anti-inflammatory markers IL-10 and IL-1Ra compared to the obese group. This study suggests that Phasa fish oil, enriched with essential fatty acid, might be used as an anti-obesity and anti-inflammatory supplement.

Cholesterol-lowering drugs, antidiabetics, antiarrhythmics, antidepressants, and antibiotics belong to the most prescribed drugs worldwide. Because of the manufacture, excretion, and improper disposal of leftover drugs, the drugs enter waste waters and, subsequently, surface waters. They have been detected in surface waters all over the world, from concentrations of ng/l to concentrations several orders of magnitude higher. Since pharmaceuticals are designed to be both biologically and chemically stable, photochemical degradation by sun radiation represents a way of transformation in the natural environment. This review provides a survey of how selected drugs of the above-mentioned classes affect aquatic organisms of different trophic level. The emphasis is on the harmful effects of phototransformation products, an area of scientific investigation that has only attracted attention in the past few years, revealing the surprising fact that products of photochemical degradation might be even more toxic to aquatic organisms than the parent drugs.

Purpose: This study investigated EEG alpha rhythm spectral power in children with Specific Language Impairment (SLI) and compared it to typically developing children to better understand the electrophysiological characteristics of this disorder. Specifically, we explored resting-state EEG, because there are studies that point to it being linked to speech and language development. Methods: EEG recordings of 30 children diagnosed with specific language impairment and 30 typically developing children, aged 4.0-6.11 years, were carried out under eyes closed and eyes open conditions. Differences in alpha rhythm spectral power in relation to brain topography and experimental conditions were calculated. Results: In the eyes closed condition, alpha rhythm spectral power was statistically significantly lower in children with specific language impairment in the left temporal (T5) and occipital electrodes (O1, O2) than in typically developing children. In the eyes open condition, children with SLI showed significantly lower alpha rhythm spectral power in the left temporal (T3, T5), parietal (P3, Pz), and occipital electrodes (O1, O2). There were no statistically significant differences between the groups in relation to the relative change (the difference between average alpha rhythm spectral power during eyes closed condition and average alpha rhythm spectral power during eyes open condition divided by average alpha rhythm spectral power during eyes closed condition) in the alpha rhythm spectral power between the conditions. Conclusion: Lower alpha rhythm spectral power in the left temporal, left, midline parietal, and occipital brain regions could be a valuable electrophysiological marker in children with SLI. Further investigation is needed to examine the connection between EEG alpha spectral power and general processing and memory deficits in patients with SLI.

Dictyophora indusiata, commonly known as bamboo fungus, is a type of edible mushroom that is highly popular worldwide for its rich flavor and nutritional value. It is also recognized for its pharmaceutical efficacy, with medicinal benefits attributed to its consumption. One of the most important components of Dictyophora indusiata is polysaccharide, which has been acknowledged as a promising regulator of biological response due to its immunostimulatory and anti-inflammatory properties. However, the specific roles of polysaccharide in modulating the NOD-like receptor protein 3 (NLRP3) inflammasome activation within macrophages remain relatively under-researched. To investigate this further, the mechanism by which Dictyophora indusiata polysaccharide (DIP) exerts its immunostimulatory activity in RAW 264.7 macrophages was analyzed. Results indicated that DIP has the potential to facilitate the priming of NLRP3 inflammasome activation by enhancing TLR4 expression, phosphorylation of IκB-α, and nuclear translocation of NF-κB p65 subunit. It was noted that DIP was unable to mediate the second step of NLRP3 inflammasome activation. The findings of this study provide compelling evidence that DIP has immunomodulatory effects by modulating the NLRP3 inflammasome in RAW264.7 macrophages.

The use of biotherapies as intervention in murine infection with Trypanosoma cruzi is a possible means to understand the effects of these highly diluted medications. This study evaluated the effects of biotherapies that were prepared from rabbit serum uninfected (BSNI_13c group) and chronically infected with Y strain of T. cruzi (BSI_13c group), dynamization 13c, in mice experimentally infected. Parasitological, histopathological, and immunological parameters were evaluated. BSNI_13c group exhibited the best outcome, including decreases in parasitemia and parasite load/inflammation in the heart, with pronounced Th1 response on days 8 and 12 after infection (a.i.) that was attributable to decrease in IL-4 concentrations, with no increases in TNF-α and IFN-γ, associated to decrease in IL-17A compared to control. In contrast, BSI_13c group did not exhibit alterations in parasitemia but a significant decrease in parasite load/inflammation in the heart, with pronounced Th2 response on day 12 a.i. that was attributable to increase in IL-4 concentrations, with no changes in TNF-α and IFN-γ, associated to decrease in IL-17A compared to control. This study suggest that biotherapies that were prepared from rabbit serum uninfected and chronically infected with T. cruzi differentially modulate the immune system in mice infected with this protozoan, providing evidence of the actions of these medications.

Oleanolic acid (OA) is a pentacyclic triterpenoid with favourable physiological activity. It is widely distributed in more than 200 species of plants. OA has garnered significant interest because of its potential biological activities, such as antioxidant, bacteriostatic, and hair growth-promoting effects. To study the effect of OA on hair growth and related mechanisms, we investigated hair growth in mice with testosterone-induced androgenetic alopecia (AGA) that were treated with three different concentrations of OA. The antioxidant, bacteriostatic, and cytotoxic effects of OA were evaluated. We found that mice with testosterone-induced AGA treated with 1% or 0.5% OA showed significantly enhanced hair growth and increased vascular endothelial growth factor/glyceraldehyde-3-phosphate dehydrogenase ratio and levels of fibroblast growth factor receptor and insulin-like growth factor 1. Using an immunofluorescence staining assay, we demonstrated that β-catenin, a key Wnt signalling transducer, was highly expressed in the OA-treated groups. These results suggest that OA may promote hair growth by stimulating hair matrix cell proliferation via the Wnt/β-catenin pathway and lowering the levels of tumour necrosis factor-alpha, and transforming growth factor-beta 1, dihydrotestosterone, and 5α-reductase.

Purpose: The aim of this study was to investigate whether luteoloside, a flavonoid, could protect human dental pulp cells (HDPCs) against inflammation and oxidative stress induced by methylglyoxal (MGO), one of the advanced glycated end products (AGE) substances. Methods: HDPCs were stimulated with MGO and treated with luteoloside. MTT assay was used to determine cell viability. Protein expression was measured via western blotting. Reactive oxygen species (ROS) were measured with a Muse Cell Analyzer. Alkaline phosphatase activity (ALP) and Alizarin red staining were used for mineralization assay. Results: Luteoloside down-regulated the expression of inflammatory molecules such as ICAM-1, VCAM-1, TNF-α, IL-1β, MMP-2, MMP-9, and COX-2 in MGO-induced HDPCs without showing any cytotoxicity. It attenuated ROS formation and enhanced osteogenic differentiation such as ALP activity and Alizarin red staining in MGO-induced HDPCs. Overall, luteoloside showed protective actions against inflammation and oxidative stress in HDPCs induced by MGO through its anti-inflammatory, anti-oxidative, and osteogenic activities by down-regulating p-JNK in the MAPK pathway. Conclusion: These results suggest that luteoloside might be a potential adjunctive therapeutic agent for treating pulpal pathological conditions in patients with diabetes mellitus.

The genus Bothrops is responsible for approximately 90% of snakebites in Brazil. In the present study biomarkers of oxidative stress (OS) were evaluated in the blood of victims of snakebites from Bothrops jararaca and Bothrops jararacussu. Patient monitoring started from the emergency entrance at the hospital up to 30 days, groups divided as follows: time 0 (t₀), 24 hours (t_24h), 7 days (t_7d) and 30 days (t_30d). The activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and myeloperoxidase (MPO), as well as the contents of reduced glutathione (GSH), vitamin E, lipid peroxidation (TBARS), protein carbonyls (PC) were examined in blood. Initial determinations revealed increased CAT, GR and GPx activities and decreased SOD and GST activities together with the depletion of GSH contents, while markers of oxidative damage showed increased TBARS levels and decreased PC concentrations in victims of snakebite compared to controls (blood donors). Regarding the temporal effect, no statistical differences among the groups were detected for the distinct parameters analyzed. The responses obtained in OS biomarkers in victims of snakebite compared to healthy subjects indicate that Bothrops envenomation promoted a pronounced and persistent systemic OS in the blood of those subjects.

Breast cancer is a serious public problem in modern society. Photodynamic therapy (PDT) is increasingly used in modern medicine. Currently, PDT is an innovative method of treating breast cancer. Irreversible damage to neoplastic tissues is associated with the use of physicochemical processes. Generating cytotoxic reactive oxygen species [singlet oxygen (1O2)] is leading to tumor cell death. At the same time, valuable information can be extracted from breast cancer cells. Photogenerated 1O2 is the major factor responsible for cell necrosis during PDT. 1O2 can react rapidly intracellularly with all organic substances. The use of photodynamic therapy on tissues in vitro creates conditions for testing various types of solutions and implementing them in in vivo treatment. This article is a review of recent advances in PDT for treatment of breast cancer. PDT is a novel cancer diagnostic and cancer treatment therapy. Therefore, an understanding of the possibility to generate a toxic form of 1O2 is necessary. The knowledge gained from the basics of PDT in vitro can be useful in biomedical applications in vivo. The current literature mentions PDT in the treatment of cancers located very deep within the human body. Therefore, the development of agents used to deliver 1O2 to the deep cancerous tissue is a new challenge which can have an efficient impact on this discipline. This review covers the literature between 2000-2022.

Background: COVID-19 is a viral disease notorious for frequent worldwide outbreaks. It is difficult to control, thereby resulting in overload of the healthcare system. A possible solution to prevent overcrowding is rapid triage of patients, which makes it possible to focus care on the high-risk patients and minimize the impact of crowding on patient prognosis. Methods: The triage algorithm assessed self-sufficiency, oximetry, systolic blood pressure, and the Glasgow coma scale. Compliance with the triage protocol was defined as fulfillment of all protocol steps, including assignment of the correct level of care. Triage was considered successful if there was no change in the scope of care (e.g., unscheduled hospital admission, transfer to different level of care) or if there was unexpected death within 48 hours. Results: A total of 929 patients were enrolled in the study. Triage criteria were fulfilled in 825 (88.8%) patients. Within 48 hours, unscheduled hospital admission, transfer to different level of care, or unexpected death occurred in 56 (6.0%), 6 (0.6%), and 5 (0.5%) patients, respectively. The risk of unscheduled hospital admission or transfer to different level of care was significantly increased if triage criteria were not fulfilled [13.1% vs. 76.1%, RR 5.8 (3.8-8.3), p < 0.001; 0.5% vs. 5.2%, RR 11.4 (2.3-57.7), p = 0.036, respectively]. Conclusion: The proposed algorithm for triage of patients with proven COVID-19 is a simple, fast, and reliable tool for rapid sorting for outpatient treatment, hospitalization on a standard ward, or assignment to an intensive care unit.

Background and objectives: It has long been known that airborne polycyclic aromatic hydrocarbons (PAHs) can negatively affect pregnancy and birth outcomes, such as birth weight, fetal development, and placental growth factors. However, similar studies yield divergent results. Our goal was to estimate the amount of monohydroxylated PAH (OH-PAH) metabolites in the urine of pregnant women/mothers and their newborns in relation to birth outcomes, such as placenta weight, Apgar 5', and the growth parameters of children up to the age of two. Methods: Two cohorts of children born in 2013 and 2014 during the summer and winter seasons in the Czech Republic in the cities Karviná (N = 144) and České Budějovice (N = 198), which differ significantly in the level of air pollution, were studied. PAH exposure was assessed by the concentration of benzo[a]pyrene (B[a]P) in the air and the concentration of 11 OH-PAH metabolites in the urine of newborns and mothers. Growth parameters and birth outcomes were obtained from medical questionnaires after birth and from pediatric questionnaires during the following 24 months of the child's life. Results: Concentrations of B[a]P were significantly higher in Karviná (p < 0.001). OH-PAH metabolites were significantly higher in the mothers' as well as in the newborns' urine in Karviná and during the winter season. Neonatal length was shorter in newborns in Karviná (p < 0.001), but this difference evened out during the next 3 to 24 months. Compared to České Budějovice, newborns in Karviná showed significantly lower weight gain between birth and three months after delivery. The OH-PAH metabolites in mothers' or newborns' urine did not affect birth weight. The presence of seven OH-PAH (top 25% of values of concentrations higher than the median) metabolites in the newborns' urine is associated with decreased length of newborn. Nine OH-PAH metabolites decreased placenta weight, which was the most significant, while seven OH-PAH metabolites decreased Apgar 5'. Conclusion: We have shown a possible connection between higher concentration of OH-PAH metabolites in newborns' urine and decreased length, head circumference, placenta weight, and Apgar 5', but not birth weight.

This study investigated whether a 30-day co-treatment with 1 g/kg glutamine dipeptide (GdiP) and 1 U/kg regular (rapid acting) or 5 U/kg degludec (long acting) insulins modifies glucose homeostasis and liver metabolism of alloxan-induced type 1 diabetic (T1D) male Swiss mice undergoing insulin-induced hypoglycemia (IIH). Glycemic curves were measured in fasted mice after IIH with 1 U/kg regular insulin. One hour after IIH, the lipid profile and AST and ALT activities were assayed in the serum. Morphometric analysis was assessed in the liver sections stained with hematoxylin-eosin and glycolysis, glycogenolysis, gluconeogenesis and ureagenesis were evaluated in perfused livers. T1D mice receiving GdiP or the insulins had a smaller blood glucose drop at 60 minutes after IIH, which was not sustained during the subsequent period up to 300 minutes. The 30-day treatment of T1D mice with insulin degludec, but not with regular insulin, improved fasting glycemia, body weight gain and serum activity of AST and ALT. Treatments with insulin degludec, GdiP and insulin degludec + GdiP decreased the liver capacity in synthesizing glucose from alanine. GdiP, in combination with both insulins, was associated with increases in the serum triglycerides and, in addition, regular insulin and GdiP increased AST and ALT activities, which could be the consequence of hepatic glycogen overload. GdiP and the insulins improved the IIH, although to a small extent. Caution is recommended, however, with respect to the use of GdiP because of its increasing effects on serum triglycerides and AST plus ALT activities.

Cannabinoids have been indicated for the treatment of glaucoma in humans. However, pharmacological studies in other species are lacking. Healthy Beagle dogs were treated with 0.1% cannabinoid eyedrops for 3 or 7 days. Intraocular pressure (IOP) and pupillary diameter (PD) were measured. To evaluate whether the topical cannabinoid formulation affects the motor and central nervous systems, a parallel study was performed. Male Swiss mice received ocular or intraperitoneal (i.p.) cannabinoid solution for 1 day (acute) or 7 days (subacute) and were tested in the open field (OF), elevated plus maze (EPM), open field habituation test (HT), and marble burying test (MBT). The treated dogs exhibited a significant reduction of IOP and PD. Acute i.p. cannabinoid administration reduced locomotion in mice in the OF and increased the number of entries into the open arms of the EPM. Subacute ocular cannabinoid administration increased the time spent on the closed arms and reduced the time spent on the open arms of the EPM. The cannabinoid i.p. and ocular did not exert anxiogenic effects in the MBT. These results indicate that the cannabinoid reduced IOP when used topically, and psychotropic effects occurred only with systemic administration.

Naringin inhibits inflammation and oxidative stress, the P2 purinoreceptor X4 receptor (P2X4R) is associated with glial cell activation and inflammation, the purpose of this study is to investigate the effects of naringin on P2X4 receptor expression on satellite glial cells (SGCs) and its possible mechanisms. ATP promoted the SGC activation and upregulated P2X4R expression; naringin inhibited SGC activation, decreased expression of P2X4R, P38 MAPK/ERK, and NF-κB, and reduced levels of Ca2+, TNF-α, and IL-1β in SGCs in an ATP-containing environment. These findings suggest that naringin attenuates the ATP-induced SGC activation and reduces P2X4R expression via the Ca2+-P38 MAPK/ERK-NF-κB pathway.

Colorectal cancer (CRC) is an important public health problem estimated as the third most commonly diagnosed cancer worldwide. Naphthoquinones are compounds present in different families of plants and interesting for medicinal chemistry due to their activities as potent inhibitors of human cancer growth. In this way, our study aimed to evaluate the cytotoxicity and selectiveness of four 2,3-triazole-1,4-naphthoquinone derivatives (N1-N4) towards the CRC cell line HT-29 and normal human cells. MTT assay showed that N1, N2, N3 and N4 elicited distinct cytotoxic potency, exhibiting EC₅₀ values of 40.6 ± 1.0, 100.1 ± 1.0, 241.9 ± 1.2 and 101.9 ± 1.1, respectively. Later, flow cytometry in HT-29 cells loaded with propidium iodide (5 μM), indicated the ability of N4 (0.5-50 μM) to induce cell membrane damage. Additionally, calcium imaging experiments were conducted in HT-29 cells loaded with 5 μM Fluo-3/AM to assess intracellular Ca²⁺ (iCa²⁺). Our data demonstrated that N4 induces a fast and strong increase of iCa²⁺ in HT-29 cells, mediated by voltage-gated L-type Ca²⁺ channels activation. In conclusion, our study reported on the cytotoxicity and selectiveness of 1,2,3-triazol substituted 1,4-naphthoquinones towards the HT-29 CRC cell line. Furthermore, we have demonstrated the participation of voltage-gated L-type Ca²⁺ channels in the N4 mechanism.

The single nucleotide polymorphism (SNP) A118G (rs1799971) in the Mu Opioid Receptor 1 (OPRM1) gene is associated with significant variations in analgesic doses and adverse effects of opioids. The A118G OPRM1 allele distributions vary significantly between different populations worldwide. The study aimed to assess the allele frequency and genotype distribution of OPRM1 A118G SNP in Saudis. This cross-sectional study included 124 healthy Saudis (62 males and 62 females) visiting the King Abdulaziz University Hospital in Jeddah, Saudi Arabia. The Oragene®-DISCOVER (OGR-600) kits were used to collect saliva samples from the participants. Polymerase chain reaction-restriction fragment length polymorphism was utilized to assess the SNP. Among the tested population, 79.03% (95% C.I. 70.81-85.82) were hom*ozygous wild-type A118A, 16.13% (95% C.I. 10.14-23.80) were heterozygous A118G, and 4.84% (95% C.I. 1.80-10.23) were hom*ozygous mutant G118G. OPRM1 A118G polymorphism allele frequencies were 87% (95% C.I. 79.89-92.44) and 13% (95% C.I. 7.56-20.11) for the 118A and 118G alleles, respectively. A higher frequency of the OPRM1 118G allele was present in females, 21% (95% C.I. 11.66-33.17) compared to males, 5% (95% C.I. 1.01-13.50). Relative to other Asian countries, the Saudi population showed a low prevalence of the OPRM1 A118G polymorphism, with a higher frequency of the 118G allele in females. Our research will contribute to the existing knowledge on the prevalence of OPRM1 A118G polymorphism, which could be considered for the personalized prescribing of opioid analgesics.

Spisulosine (1-deoxysphinganine) is a sphingoid amino alcohol isolated from the sea clams that showed potent antiproliferative activity against a broad spectrum of solid tumors but failed in clinical trials due to neurotoxicity. However, its structural similarity to other bioactive sphingoids, interesting mode of action, and appreciable potency against cancer cells make it a suitable lead for future anticancer drug development. The present study was conducted to elucidate mechanisms of the antiproliferative/cytotoxic effects of newly synthesized spisulosine analog hom*ospisulosine (KP7). The evaluation was performed on cervical carcinoma cells, representing an in vitro model of one of the most common cancer types and a significant worldwide cause of women's cancer mortality. Treatment with hom*ospisulosine (2.0 μM) for 24, 48, and 72 h significantly inhibited the growth of HeLa cells in vitro and induced apoptosis detectable by DNA fragmentation, externalization of phosphatidylserine, dissipation of mitochondrial membrane potential, activation of caspase-3 and cleavage of PARP. In addition, treating HeLa cells with spisulosine increased p27 and Bcl-2 on protein levels and phosphorylation of Bcl-2 on Ser70 residue. These results support the potential for spisulosine analogs represented here by hom*ospisulosine for future therapeutic development.

Introduction: This study aimed to identify the phytochemical constituents that could target gastric cancer in Kangai injection using a network pharmacology-based approach. Methods: Protein-protein interactions (PPI), Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted utilizing String and OmicShare tools. In the in vitro experiments, the related mRNA and protein levels were assessed via real-time quantitative polymerase chain reaction and Western blotting, respectively. Cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Results: Kangai injection comprises several compounds, which target multiple substrates and pathways related to gastric cancer. The PPI and Gene Ontology analyses revealed that tumor necrosis factor (TNF) was a hub gene. KEGG pathway enrichment analysis indicated that the the TNF pathway was significantly enriched. Kangai injection decreased the mRNA levels of TNFR2, TRAF2, PI3K, AKT, and IκBα and inhibited the phosphorylation of PI3K, AKT, and IκBα phosphorylations. Kangai injection inhibited cell proliferation, while TNFR2 overexpression or treatment with the PI3K activator 740 Y-P partially restored it. Conclusion: Kangai injection operates through multiple targets and pathways in gastric cancer, with the TNFR2/PI3K/AKT/NF-κB pathway playing a crucial role in its mechanism against gastric cancer.