Search Results (14)

Background/Objectives: Mirtazapine (MRZ) is a psychotropic drug prescribed to manage serious sorts of depression. By virtue of its extensive initial-pass metabolic process with poor water solubility, the ultimate bioavailability when taken orally is a mere 50%, necessitating repeated administration. The current inquiry intended to fabricate nose-to-brain chitosan-grafted cationic leciplexes of MRZ (CS-MRZ-LPX) to improve its pharmacokinetic weaknesses and boost the pharmacodynamics aspects. Methods: Primarily, MRZ-loaded leciplexes (MRZ-LPXs) were fabricated and tailored employing a central composite design (CCD). Vesicle diameter size (VS), entrapment efficiency (EE %), cumulative MRZ release percentage (CMRZR %), and total quantity penetrating after twenty-four hours (Q24) were the four parameters assessed. Then, the determined optimum formulation was coated with chitosan (CS-MRZ-LPX) and utilized in pharmacodynamics investigations and in vivo biologic distribution studies in Wistar male rats. Results: The customized MRZ-LPX formulation had a diameter size of 186.2 ± 3.5 nm and drug EE of 45.86 ± 0.76%. Also, the tailored MRZ-LPX formulation had a cumulative amount of MRZ released of 76.66 ± 3.06% and the total Q24 permeated was 383.23 ± 13.08 µg/cm². Intranasal delivery of the tailored CS-MRZ-LPX revealed notably superior pharmacokinetic attributes inside the brain and circulation compared to the orally administered MRZ suspension and the intranasal free drug suspension (p < 0.05); the relative bioavailability was 370.9% and 385.6% for plasma and brain, respectively. Pharmacodynamics’ and immunohistopathological evaluations proved that optimum intranasal CS-MRZ-LPX boosted antidepressant activity compared to the oral and free nasal drug administration. Conclusions: CS-MRZ-LPX tailored formulation can potentially be regarded as a prospective nano platform to boost bioavailability and enhance pharmacodynamics efficacy. Ultimately, intranasal CS-MRZ-LPX can be considered a promising avenue for MRZ targeted brain delivery as an antidepressant. Full article

Cataract surgery can lead to inflammatory processes in the retina due to its invasive nature, resulting in prolonged recovery times and reduced functional outcomes. The aim of the current study is to explore the impact that phacoemulsification parameters have on macular thickness following surgery. This prospective single-center study enrolled 46 healthy patients (46 eyes) who underwent uneventful cataract surgery. Retinal thickness was assessed using optical coherence tomography (OCT) preoperatively, as well as 1, 4, and 12 weeks after surgery. The macula was divided into a central (CMT), inner (IMT), and outer ring (OMT). Cataract density was automatically determined using an anterior segment OCT and a custom MATLAB script. Corrected distance visual acuity (CDVA), intraocular pressure (IOP) as well as cumulative dissipated energy (CDE), ultrasound time (UT), and fluids used during phacoemulsification were recorded. Retinal thickness and volume increased significantly following cataract surgery, reaching its maximum 4 weeks post-operatively. Statistically significant correlations were found between the CDE and IMT, OMT and retinal volume change (r_IMT = 0.356, r_OMT = 0.298, rvolume = 0.357 with p < 0.05) as well as between the ultrasound time and IMT, OMT, and retinal volume change (r_IMT = 0.369, r_OMT = 0.293 and r_volume = 0.409 with p < 0.05). Changes in CMT did not correlate with any surgical metrics. Additionally, no correlation was found to the amount of fluid used, whether CDVA or IOP. However, a link between nuclear cataract density and changes in OMT (r = 0.310, p < 0.05) was established. How ultrasound energy impacts the choroidea, and to what extent retinal metabolism changes after surgery, needs to be explored in future studies. Full article

Cadmium (Cd) is a toxic metal for the human organism and for all ecosystems. Cd is naturally found at low levels; however, higher amounts of Cd in the environment result from human activities as it spreads into the air and water in the form of micropollutants as a consequence of industrial processes, pollution, waste incineration, and electronic waste recycling. The human body has a limited ability to respond to Cd exposure since the metal does not undergo metabolic degradation into less toxic species and is only poorly excreted. The extremely long biological half-life of Cd essentially makes it a cumulative toxin; chronic exposure causes harmful effects from the metal stored in the organs. The present paper considers exposure and potential health concerns due to environmental cadmium. Exposure to Cd compounds is primarily associated with an elevated risk of lung, kidney, prostate, and pancreatic cancer. Cd has also been linked to cancers of the breast, urinary system, and bladder. The multiple mechanisms of Cd-induced carcinogenesis include oxidative stress with the inhibition of antioxidant enzymes, the promotion of lipid peroxidation, and interference with DNA repair systems. Cd²⁺ can also replace essential metal ions, including redox-active ones. A total of 12 cancer types associated with specific genes coding for the Cd-metalloproteome were identified in this work. In addition, we summarize the proper treatments of Cd poisoning, based on the use of selected Cd detoxifying agents and chelators, and the potential for preventive approaches to counteract its chronic exposure. Full article

Dark fermentation is a hydrogen generating process carried out by anaerobic spore-forming bacteria that metabolize carbon sources producing gas and short-chain acids. The process can be controlled, and the hydrogen harvested if bacteria are grown in a reactor with favorable conditions. In this work, bacteria selected from natural sources were grown with a defined culture media, while pH was monitored, with the aim of relating the amount of generated hydrogen to the increase in hydron ion concentration. Therefore, a model based on the acid-base species mass balance is proposed and solved to estimate the lag phase time and measure the hydrogen production efficiency and kinetics. Hydrogen production in a stirred batch reactor was performed for 150–200 h, at given operating conditions using a previously defined growth media, to validate the model. Using the proposed model, the cumulated moles of produced hydrogen correlate well with those predicted from the pH curve. Hence, the modified Gompertz model parameters, largely used for describing the hydrogen generation kinetics by dark fermentation, were estimated from the pH curve and from the experimentally measured generated hydrogen. Satisfactory agreement was found, thus, validating the method. Full article

Skeletal muscle is a highly adaptable organ, and its amount declines under catabolic conditions such as critical illness. Aging is accompanied by a gradual loss of muscle, especially when physical activity decreases. Intensive care unit-acquired weakness is a common and highly serious neuromuscular complication in critically ill patients. It is a consequence of critical illness and is characterized by a systemic inflammatory response, leading to metabolic stress, that causes the development of multiple organ dysfunction. Muscle dysfunction is an important component of this syndrome, and the degree of catabolism corresponds to the severity of the condition. The population of critically ill is aging; thus, we face another negative effect—sarcopenia—the age-related decline of skeletal muscle mass and function. Low-grade inflammation gradually accumulates over time, inhibits proteosynthesis, worsens anabolic resistance, and increases insulin resistance. The cumulative consequence is a gradual decline in muscle recovery and muscle mass. The clinical manifestation for both of the above conditions is skeletal muscle weakness, with macromolecular damage, and a common mechanism—mitochondrial dysfunction. In this review, we compare the molecular mechanisms underlying the two types of muscle atrophy, and address questions regarding possible shared molecular mechanisms, and whether critical illness accelerates the aging process. Full article

Vegetation restoration can affect the process of soil organic carbon (SOC) decomposition, but how this effect is related to soil moisture and temperature remains uncertain. Thus, we performed an incubation of 120 days using soils of degraded land, plantation forest, and secondary natural forest, at two levels of temperature under two moisture levels. We found that the amount of cumulative SOC decomposition in the plantation and secondary natural forest soil was ca. 11.7 times higher than that in the soil from degraded land. Higher soil moisture and temperature treatment increased SOC decomposition in the plantation and secondary natural forest soils. However, in the soil from degraded land, higher soil moisture did not increase SOC decomposition, and higher temperature only increased SOC decomposition in the 60%WHC treatment. The amount of cumulative SOC decomposition was positively correlated with soil MBC and DOC content. The responses of SOC decomposition and the decomposability of DOC to moisture and temperature along the vegetation restoration gradient were highly consistent. Furthermore, in the 60%WHC treatment group, the temperature sensitivity (Q₁₀) of SOC decomposition declined with vegetation restoration age increase. Higher soil moisture did not affect Q₁₀ in the plantation and secondary natural forest soil, but increased Q₁₀ in the soil from degraded land. Our results indicate that higher soil temperature and moisture would stimulate SOC decomposition, but it is highly dependent on labile carbon supply and microbial metabolic activity along the vegetation restoration gradient. Full article

Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the most common liver disorders worldwide and the major causes of non-viral liver cirrhosis in the general population. In NAFLD, metabolic abnormalities, obesity, and metabolic syndrome are the driving factors for liver damage with no or minimal alcohol consumption. ALD refers to liver damage caused by excess alcohol intake in individuals drinking more than 5 to 10 daily units for years. Although NAFLD and ALD are nosologically considered two distinct entities, they show a continuum and exert synergistic effects on the progression toward liver cirrhosis. The current view is that low alcohol use might also increase the risk of advanced clinical liver disease in NAFLD, whereas metabolic factors increase the risk of cirrhosis among alcohol risk drinkers. Therefore, special interest is now addressed to individuals with metabolic abnormalities who consume small amounts of alcohol or who binge drink, for the role of light-to-moderate alcohol use in fibrosis progression and clinical severity of the liver disease. Evidence shows that in the presence of NAFLD, there is no liver-safe limit of alcohol intake. We discuss the epidemiological and clinical features of NAFLD/ALD, aspects of alcohol metabolism, and mechanisms of damage concerning steatosis, fibrosis, cumulative effects, and deleterious consequences which include hepatocellular carcinoma. Full article

Anthropogenic activities release large amounts of nitrogen (N) and phosphorus (P) nutrients into the environment. Sources of nutrients include surface and sub-surface runoffs from agricultural practices with the application of chemical fertilizers and manure as well as combined sewer overflows (CSOs). Nutrient runoffs contribute to the eutrophication of aquatic ecosystems and enhance the growth of cyanobacteria. Precipitation is an important driving force behind the runoff of nutrients from agricultural fields into surrounding water bodies. To understand the dynamics between nutrient input, precipitation and cyanobacterial growth in Missisquoi Bay, Lake Champlain (Quebec), one location in Pike River (a major tributary into the bay) and four locations in Missisquoi Bay were monitored from April to November in 2017 and 2018. Biweekly water samples were analyzed using chemical methods and high-throughput sequencing of 16S rRNA gene amplicons. High concentrations of N and P were typically measured in April and May. Three major spikes in nutrient concentrations were observed in early and mid-summer as well as early fall, all of which were associated with intense cumulative precipitation events of 40 to 100 mm within 7 days prior to sampling. Despite the high concentrations of nutrients in the spring and early summer, the cyanobacterial blooms appeared in mid to late summer as the water temperature increased. Dolichospermum sp. was the major bloom-forming cyanobacterium during both summers. A second intense bloom event of Microcystis was also observed in the fall (October and November) for both years. Variation in the cyanobacteria population was strongly associated with inorganic and readily available fractions of N and P such as nitrites and nitrates (NOx), ammonia (NH₃) and dissolved organic phosphorus (DOP). During blooms, total Kjeldahl nitrogen (TKN) and total particulate phosphorus (TPP) fractions had a substantial influence on total nitrogen (TN) and total phosphorus (TP) concentrations, respectively. The abundance of bacteria involved in the metabolism of nitrogen compared to that of phosphorus revealed the importance of nitrogen on overall microbial dynamics as well as CB formation in the bay. Our findings emphasize the combined influence of precipitation events, temperature and several bioavailable fractions of nitrogen and phosphorus on cyanobacterial bloom episodes. Full article

Background and Aims: In the general population, previous studies reported that physical activity was associated with risk of hepatocellular carcinoma (HCC) development. However, it is unclear whether physical activity is associated with risk of HCC development in patients with chronic hepatitis B (CHB). We aimed to elucidate the association between physical activity and risk of HCC development in CHB patients. Methods: This nationwide cohort study involved treatment-naive patients with CHB (n = 9727) who started treatment with entecavir or tenofovir and answered self-reported questionnaires between January 2012 and December 2017, using data from the Korean National Health Insurance Service database. The primary endpoint was development of HCC. Multivariable Cox regression and competing risk analyses were used. Results: During a median follow-up of 3.1 years, cumulative HCC incidence rates were 8.3%. There was an inverse association between physical activity and the risk of HCC (p < 0.001). Patients with 1000–1500 metabolic equivalent task (MET)-min/week, compared to those without physical activity, showed a significantly lower risk of HCC in both patients without cirrhosis (adjusted hazard ratio [aHR] 0.66, p = 0.02) and patients with cirrhosis (aHR 0.61, p = 0.02). In patients who were younger (<60), male, without diabetes, and with high BMI, amounts of physical activity of 1000–1500 MET-min/week showed an inverse association with the risk of HCC (aHR 0.65, 0.63, 0.65, and 0.64, respectively, all p < 0.05). Conclusion: Physical activity was significantly associated with a low risk of HCC in CHB patients treated with entecavir or tenofovir. Full article

Pyrroloquinoline quinone (PQQ) is a novel stimulator of mitochondrial biogenesis and cellular energy metabolism. This is the first study investigating regulatory mechanisms and metabolic responses underlying PQQ’s action in palmitate-exposed L6 myotubes. Particularly, we assessed alterations in lipid content and composition, expression of metabolic enzymes, and changes in glucose transport. The experiments were conducted using muscle cells subjected to short (2 h) and prolonged (24 h) incubation with PQQ in a sequence of pre- and post-palmitic acid (PA) exposure. We demonstrated the opposite effects of 2 and 24 h treatments with PQQ on lipid content, i.e., a decline in the level of free fatty acids and triacylglycerols in response to short-time PQQ incubation as compared to increases in diacylglycerol and triacylglycerol levels observed after 24 h. We did not demonstrate a significant impact of PQQ on fatty acid transport. The analysis of metabolic enzyme expression showed that the vast majority of PQQ-dependent alterations cumulated in the PA/PQQ 24 h group, including elevated protein amount of peroxisome proliferator activated receptor γ co-activator 1α (PGC-1α), sirtuin-1 (SIRT1), phosphorylated 5′AMP-activated protein kinase (pAMPK), carnitine palmitoyltransferase I (CPT1), citrate synthase (CS), fatty acid synthase (FAS), and serine palmitoyltransferase, long chain base subunit 1 (SPT1). In conclusion, the results mentioned above indicate PQQ-dependent activation of both fatty acid oxidation and lipid synthesis in order to adapt cells to palmitic acid-rich medium, although PQQ did not attenuate insulin resistance in muscle cells. Full article

Obesity is a metabolic disease characterized by an increased risk of type 2 diabetes, hypertension, and cardiovascular disease. We have previously reported that compounds isolated from brown alga, Sargassum thunbergii (ST; Sargassum thunbergii (Mertens ex Roth) Kuntze), inhibit adipogenesis in 3T3-L1 cells. However, the in vivo anti-obesity effects of these compounds have not been previously reported. Therefore, the objective of this study was to determine the effects of ST on weight loss, fat accumulation, as well as risk factors for type 2 diabetes and cardiovascular disease in high-fat diet (HFD)-induced obese mice. ST treatment significantly decreased body weight and fat accumulation in HFD-induced obese mice, while reducing insulin and factors related to cardiovascular diseases (triglyceride and total cholesterol) in serum. ST-induced downregulation of PPARγ in white adipose tissue, and upregulation of the thermogenic genes, UCP-1 and UCP-3, in brown adipose tissue was also observed. In addition, oral administration of ST reduced the occurrence of fatty liver, as well as the amount of white adipose tissue in HFD mice. Cumulatively, these results suggest that ST exerts anti-obesity effects and may serve as a potential anti-obesity therapeutic agent. Full article

Topical drug delivery is an attractive alternative to conventional methods because of advantages such as non-invasive delivery, by-pass of first pass metabolism, and improved patient compliance. However, several factors such as skin, physicochemical properties of the drug, and vehicle characteristics influence the permeation. Within a formulation, critical factors such as concentration of drug, physical state of drug in the formulation, and organoleptic properties affect the flux across the skin. The aim of the study was to develop and investigate topical semisolid preparations (creams and gels) with ibuprofen as the model drug and investigate the effect of various formulation parameters on the in-vitro performance across the Strat-M^® membrane using flow-through cells. In addition, the physical stability of the developed formulations was investigated by studying viscosity, pH, and appearance. All the formulations developed in the study had appealing appearance with smooth texture and no signs of separation. Viscosity and pH of the formulations were acceptable. Cumulative amount of drug permeated at the end of 24 h was highest for clear gel (3% w/w ibuprofen; F6: 739.6 ± 36.1 µg/cm²) followed by cream with high concentration of ibuprofen in suspended form (5% w/w; F3: 320.8 ± 17.53 µg/cm²), emulgel (3% w/w ibuprofen; F5: 178.5 ± 34.5 µg/cm²), and cream with solubilized ibuprofen (3% w/w; F2A: 163.2 ± 9.36 µg/cm²). Results from this study showed that permeation of ibuprofen was significantly influenced by formulation parameters such as concentration of ibuprofen (3% vs. 5% w/w), physical state of ibuprofen (solubilized vs. suspended), formulation type (cream vs. gel), mucoadhesive agents, and viscosity (high vs. low). Thus, findings from this study indicate that pharmaceutical formulation scientists should explore these critical factors during the early development of any new topical drug product in order to meet pre-determined quality target product profile. Full article

As an open artificial ecosystem, the development of a city requires the continuous input and output of material and energy, which is called urban metabolism, and includes catabolic (material-flow) and anabolic (material-accumulation) processes. Previous studies have focused on the catabolic and ignored the anabolic process due to data and technology problems. The combination of remote-sensing technology and high-resolution satellite images facilitates the estimation of cumulative material amounts in urban systems. This study focused on persistent accumulation, which is the metabolic response of urban land use/urban land expansion, building stock, and road stock to land-use changes. Building stock is an extremely cost-intensive and long-lived component of cumulative metabolism. The study measured building stocks of Jinchang, China’s nickel capital by using remote-sensing images and field-research data. The development of the built environment could be analyzed by comparing the stock of buildings on maps representing different time periods. The results indicated that material anabolism in Jinchang is a distance-dependent function, where the amounts and rates of material anabolism decrease with changes in distance to the central business district (CBD) and city administration center (CAC). The cumulative metabolic rate and cumulative total metabolism were observed to be increasing, however, the growth rate has decreased. Full article

One of primary issues in the coffee manufacturing industry is the production of large amounts of undesirable residues, which include the pericarp (outer skin), pulp (outer mesocarp), parchment (endocarp), silver-skin (epidermis) and mucilage (inner mesocarp) that cause environmental problems due to toxic molecules contained therein. This study evaluated the optimal hydrogen production from coffee mucilage combined with organic wastes (wholesale market garbage) in a dark fermentation process. The supplementation of organic wastes offered appropriate carbon and nitrogen sources with further nutrients; it was positively effective in achieving cumulative hydrogen production. Three different ratios of coffee mucilage and organic wastes (8:2, 5:5, and 2:8) were tested in 30 L bioreactors using two-level factorial design experiments. The highest cumulative hydrogen volume of 25.9 L was gained for an 8:2 ratio (coffee mucilage: organic wastes) after 72 h, which corresponded to 1.295 L hydrogen/L substrates (0.248 mol hydrogen/mol hexose). Biochemical identification of microorganisms found that seven microorganisms were involved in the hydrogen metabolism. Further studies of anaerobic fermentative digestion with each isolated pure bacterium under similar experimental conditions reached a lower final hydrogen yield (up to 9.3 L) than the result from the non-isolated sample (25.9 L). Interestingly, however, co-cultivation of two identified microorganisms (Kocuria kristinae and Brevibacillus laterosporus), who were relatively highly associated with hydrogen production, gave a higher yield (14.7 L) than single bacterium inoculum but lower than that of the non-isolated tests. This work confirms that the re-utilization of coffee mucilage combined with organic wastes is practical for hydrogen fermentation in anaerobic conditions, and it would be influenced by the bacterial consortium involved. Full article