Miracle-dz/UniFAR-FTUs huggingface dataset:
Antiangiogenic Drugs in NASH: Evidence of a Possible New Therapeutic Approach

Non-alcoholic fatty liver disease is the most common liver disorder worldwide, and its progressive form non-alcoholic steatohepatitis (NASH) is a growing cause of liver cirrhosis and hepatocellular carcinoma (HCC). Lifestyle changes, which are capable of improving the prognosis, are hard to achieve, whereas a pharmacologic therapy able to combine efficacy and safety is still lacking. Looking at the pathophysiology of various liver diseases, such as NASH, fibrosis, cirrhosis, and HCC, the process of angiogenesis is a key mechanism influencing the disease progression. The relationship between the worsening of chronic liver disease and angiogenesis may suggest a possible use of drugs with antiangiogenic activity as a tool to stop or slow the progression of the disorder. In this review, we highlight the available preclinical data supporting a role of known antiangiogenic drugs (e.g., sorafenib), or phytotherapeutic compounds with multiple mechanism of actions, including also antiangiogenic activities (e.g., berberine), in the treatment of NASH.
Development and Evaluation of Amorphous Oral Thin Films Using Solvent-Free Processes: Comparison between 3D Printing and Hot-Melt Extrusion Technologies

Conventional oral dosage forms may not always be optimal especially for those patients suffering from dysphasia or difficulty swallowing. Development of suitable oral thin films (OTFs), therefore, can be an excellent alternative to conventional dosage forms for these patient groups. Hence, the main objective of the current investigation is to develop oral thin film (OTF) formulations using novel solvent-free approaches, including additive manufacturing (AM), hot-melt extrusion, and melt casting. AM, popularly recognized as 3D printing, has been widely utilized for on-demand and personalized formulation development in the pharmaceutical industry. Additionally, in general active pharmaceutical ingredients (APIs) are dissolved or dispersed in polymeric matrices to form amorphous solid dispersions (ASDs). In this study, acetaminophen (APAP) was selected as the model drug, and Klucel™ hydroxypropyl cellulose (HPC) E5 and Soluplus® were used as carrier matrices to form the OTFs. Amorphous OTFs were successfully manufactured by hot-melt extrusion and 3D printing technologies followed by comprehensive studies on the physico-chemical properties of the drug and developed OTFs. Advanced physico-chemical characterizations revealed the presence of amorphous drug in both HME and 3D printed films whereas some crystalline traces were visible in solvent and melt cast films. Moreover, advanced surface analysis conducted by Raman mapping confirmed a more homogenous distribution of amorphous drugs in 3D printed films compared to those prepared by other methods. A series of mathematical models were also used to describe drug release mechanisms from the developed OTFs. Moreover, the in vitro dissolution studies of the 3D printed films demonstrated an improved drug release performance compared to the melt cast or extruded films. This study suggested that HME combined with 3D printing can potentially improve the physical properties of formulations and produce OTFs with preferred qualities such as faster dissolution rate of drugs.
The Influence of Nordic Walking on Spinal Posture, Physical Function, and Back Pain in Community-Dwelling Older Adults: A Pilot Study

Nordic walking is an increasingly popular form of exercise among the elderly. Using poles is thought to facilitate a more upright posture; however, previous studies primarily investigated the effects of Nordic walking on respiratory function and physical fitness. The aims of this study were to investigate the influence of Nordic walking on spinal posture, physical functions, and back pain in community-dwelling older adults. Thirty-one community-dwelling older adults aged ≥ 60 years participated in a twice weekly Nordic walking training program for 12 weeks. The outcome measures, including spinal posture, physical functions, back pain, and the strength and endurance of back extensor muscles were assessed before and after a 12-week program. After training, spinal posture, back pain, and the strength and endurance of back extensor muscles did not show any statistically significant changes. Among the seven clinical tests of physical function, only the 30 s arm curl test, the 30 s chair stand test, and the single leg stance test showed significant improvements. Nordic walking has limited influence on age-related hyperkyphosis and back pain, but may be effective for physical function. The results of this study can provide useful information for people involved in the prevention and treatment of physical dysfunction in community-dwelling older adults.
Perspective on Stem Cell Therapy in Organ Fibrosis: Animal Models and Human Studies

Tissue fibrosis is characterized by excessive deposition of extracellular matrix (ECM) components that result from the disruption of regulatory processes responsible for ECM synthesis, deposition, and remodeling. Fibrosis develops in response to a trigger or injury and can occur in nearly all organs of the body. Thus, fibrosis leads to severe pathological conditions that disrupt organ architecture and cause loss of function. It has been estimated that severe fibrotic disorders are responsible for up to one-third of deaths worldwide. Although intensive research on the development of new strategies for fibrosis treatment has been carried out, therapeutic approaches remain limited. Since stem cells, especially mesenchymal stem cells (MSCs), show remarkable self-renewal, differentiation, and immunomodulatory capacity, they have been intensively tested in preclinical studies and clinical trials as a potential tool to slow down the progression of fibrosis and improve the quality of life of patients with fibrotic disorders. In this review, we summarize in vitro studies, preclinical studies performed on animal models of human fibrotic diseases, and recent clinical trials on the efficacy of allogeneic and autologous stem cell applications in severe types of fibrosis that develop in lungs, liver, heart, kidney, uterus, and skin. Although the results of the studies seem to be encouraging, there are many aspects of cell-based therapy, including the cell source, dose, administration route and frequency, timing of delivery, and long-term safety, that remain open areas for future investigation. We also discuss the contemporary status, challenges, and future perspectives of stem cell transplantation for therapeutic options in fibrotic diseases as well as we present recent patents for stem cell-based therapies in organ fibrosis.
Therapeutic Liquid Formulations Based on Low Transition Temperature Mixtures for the Incorporation of Anti-Inflammatory Drugs

Most nonsteroidal anti-inflammatory drugs (NSAIDs) present poor aqueous solubility, impairing their efficiency in physiological media. In this context, Low Transition Temperature Mixtures (LTTMs) are a promising platform to overcome drugs’ poor solubility, forming therapeutic liquid formulations. In this work, the LTTMs of citric acid:L-arginine:water (C:A:W) and glycerol:sorbitol (G:S) were studied in terms of their features and assessed in terms of their ability to increase the solubility of six NSAIDs in physiological media. The physicochemical properties of LTTMs were characterized by state-of-art techniques commonly used for these systems. The cytotoxicity of G:S was also evaluated in L929 mouse fibroblasts and the viscosity, polarity, and pH properties of the studied mixtures were related to the solubility of NSAIDs. The pH and polarity were the parameters that most influenced the drugs’ solubility. Ibuprofen, naproxen, ketoprofen, indomethacin, and flurbiprofen did not present any solubility improvement in the formulations tested. However, concentrated mixtures of C:A:W or G:S in the physiologic-mimicked media (PBS) rendered a celecoxib solubility 4 and 5 times higher than PBS, respectively. These therapeutic liquid formulations of celecoxib in C:A:W or G:S can be a promising tool to increase celecoxib’s therapeutic efficiency in local applications.
Relationship between Nutritional Status and Clinical Outcome in Patients Treated for Lung Cancer

Background. Between 34.5% and 69% of the patients with lung cancer are at risk of malnutrition. Quality of life (QoL) and physical status assessment provides valuable prognostic data on lung cancer patients. Malnutrition is a prognostic parameter for clinical outcome. Therefore, the identification of significant factors affecting the clinical outcome and QoL is important. The purpose of this study was to evaluate the relationship between nutritional status and outcome, i.e., overall survival, time to tumor progression, and QoL, in lung cancer patients. Materials and methods. We performed a systematic search of the Pubmed/MEDLINE databases per the Cochrane guidelines to conduct a meta-analysis consistent with the PRISMA statement, using the following keywords: “lung cancer,” “malnutrition,” “nutrition,” “quality of life,” “well-being,” “health-related quality of life,” and “outcome. ” Out of the 96 papers identified, 12 were included in our meta-analysis. Results. Our meta-analysis shows that patients with a good nutritional status have a better QoL than malnourished patients in the following functioning domains: physical (g = 1.22, 95% CI = 1.19 to 1.46, p < 0.001), role (g = 1.45, 95% CI = 1.31 to 1.59, p < 0.001), emotional (g = 1.10, 95% CI = 0.97 to 1.24, p < 0.001), cognitive (g = 0.91, 95% CI = 0.76 to 1.06, p < 0.001), and social (g = 1.41, 95% CI = 1.27 to 1.56, p < 0.001). The risk of death was significantly higher in malnourished than in well-nourished patients (HR = 1.53, 95% CI = 1.25 to 1.86, p < 0.001). Nutritional status was significantly associated with survival, indicating that patients with a poorer nutritional status are at more risk of relapse. Conclusions. Nutritional status is a significant clinical and prognostic parameter in the assessment of lung cancer treatment. Malnutrition is associated with poorer outcome in terms of overall survival, time to tumor progression, and QoL in patients treated for lung cancer.
Advances in Sintering Techniques for Calcium Phosphates Ceramics

Calcium phosphate (CaP) biomaterials are extensively used to reconstruct bone defects. They resemble a chemical similarity to the inorganic mineral present in bones. Thus, they are termed as the key players in bone regeneration. Sintering is a heat treatment process applied to CaP powder compact or fabricated porous material to impart strength and integrity. Conventional sintering is the simplest sintering technique, but the processing of CaPs at a high temperature for a long time usually leads to the formation of secondary phases due to their thermal instability. Furthermore, it results in excessive grain growth that obstructs the densification process, limiting the application of CaP’s ceramics in bone regeneration. This review focuses on advanced sintering techniques used for the densification of CaPs. These techniques utilize the synergy of temperature with one or more parameters such as external pressure, electromagnetic radiation, electric current, or the incorporation of transient liquid that boosts the mass transfer while lowering the sintering temperature and time.
High-Throughput Sequencing of Circulating MicroRNAs in Plasma and Serum during Pregnancy Progression

Although circulating microRNAs (miRNAs) in maternal blood may play an important role in regulation of pregnancy progression and serve as non-invasive biomarkers for different gestation complications, little is known about their profile in blood during normally developing pregnancy. In this study we evaluated the miRNA profiles in paired plasma and serum samples from pregnant women without health or gestational abnormalities at three time points using high-throughput sequencing technology. Sequencing revealed that the percentage of miRNA reads in plasma and serum decreased by a third compared to first and second trimesters. We found two miRNAs in plasma (hsa-miR-7853-5p and hsa-miR-200c-3p) and 10 miRNAs in serum (hsa-miR-203a-5p, hsa-miR-495-3p, hsa-miR-4435, hsa-miR-340-5p, hsa-miR-4417, hsa-miR-1266-5p, hsa-miR-4494, hsa-miR-134-3p, hsa-miR-5008-5p, and hsa-miR-6756-5p), that exhibit level changes during pregnancy (p-value adjusted < 0.05). In addition, we observed differences for 36 miRNAs between plasma and serum (p-value adjusted < 0.05), which should be taken into consideration when comparing the results between studies performed using different biosample types. The results were verified by analysis of three miRNAs using qRT-PCR (p < 0.05). The present study confirms that the circulating miRNA profile in blood changes during gestation. Our results set the basis for further investigation of molecular mechanisms, involved in regulation of pregnancy, and the search for biomarkers of gestation abnormalities.
General Limitations to Endophytic Entomopathogenic Fungi Use as Plant Growth Promoters, Pests and Pathogens Biocontrol Agents

The multiple roles of fungal entomopathogens in host plants’ growth promotion, pest and pathogen management have drawn huge attention for investigation. Endophytic species are known to influence various activities of their associated host plants, and the endophyte-colonized plants have been demonstrated to gain huge benefits from these symbiotic associations. The potential application of fungal endophytes as alternative to inorganic fertilizers for crop improvement has often been proposed. Similarly, various strains of insect pathogenic fungi have been formulated for use as mycopesticides and have been suggested as long-term replacement for the synthetic pesticides that are commonly in use. The numerous concerns about the negative effects of synthetic chemical pesticides have also driven attention towards developing eco-friendly pest management techniques. However, several factors have been underlined to be militating the successful adoption of entomopathogenic fungi and fungal endophytes as plant promoting, pests and diseases control bio-agents. The difficulties in isolation and characterization of novel strains, negative effects of geographical location, vegetation type and human disturbance on fungal entomopathogens, are among the numerous setbacks that have been documented. Although, the latest advances in biotechnology and microbial studies have provided means of overcoming many of these problems. For instance, studies have suggested measures for mitigating the negative effects of biotic and abiotic stressors on entomopathogenic fungi in inundative application on the field, or when applied in the form of fungal endophytes. In spite of these efforts, more studies are needed to be done to achieve the goal of improving the overall effectiveness and increase in the level of acceptance of entomopathogenic fungi and their products as an integral part of the integrated pest management programs, as well as potential adoption as an alternative to inorganic fertilizers and pesticides.
Primary Immune Thrombocytopenia and Essential Thrombocythemia: So Different and yet Somehow Similar—Cases Series and a Review of the Literature

This article collects several published cases in which immune thrombocytopenic purpura (ITP) is followed by essential thrombocythemia (ET) and vice versa. This surprising clinical condition is possible, but very rare and difficult to diagnose and manage. We have made an attempt to analyse the possible causes of the sequential appearance of ITP and ET taking into consideration the following: alteration of the thrombopoietin (TPO) receptor, the role of autoimmunity and inflammation, and cytokine modulation. A better understanding of these interactions may provide opportunities to determine predisposing factors and aid in finding new treatment modalities both for ITP and ET patients.
Current opinion on the diagnosis and management of non-functioning pituitary adenomas

ABSTRACT Introduction Non-functioning pituitary adenomas (NFPAs) are clinically silent tumors and the second most common pituitary adenoma. Surgery is the mainstay of treatment as there is, as yet, no effective medical treatment. Areas covered We present current knowledge on the clinical diagnosis, histopathological classification, molecular data, and management strategies in NFPA. Expert opinion NFPA is a heterogeneous group of tumors, in respect to their origin and clinical course. In recent years, research on pathology and molecular biology have advanced our knowledge of NFPA pathogenesis. NFPA exhibit, in the majority of cases, an indolent behavior, with satisfactory response to treatment. In aggressive cases, multimodal management is needed; however, even this approach may be insufficient, so the development of new treatments is warranted for better management. In this setting, the understanding of the mechanisms involved in the genesis and progression of NFPA is crucial for the identification and development of directed treatments with higher chances of response.
Evaluation of maximum thigh angular acceleration during the swing phase of steady-speed running.

The hip joint and surrounding musculature must generate and withstand torque during the swing phase of running. Prior research has demonstrated that sagittal plane hip torque increases with speed, indicating that thigh angular acceleration likely increases in a similar manner and may be an important gait parameter. In this investigation, we modelled thigh angle vs. time data with a sine wave function, requiring inputs of thigh angular amplitude and stride frequency. This enabled a simple formula to model maximum thigh angular acceleration (αmax, rad/s2) during the swing phase of steady-speed running. A total of 40 participants (20 male, 20 female) completed submaximal and maximal 40 m running trials (n = 154 trials, speed range: 3.1-10.0 m/s), with kinematic data collected from 31-39 m. Thigh angle vs. time curves were well fit by a sine wave function (mean R2 > 0.94 across all trials) and modelled αmax was highly correlated with top speed (R2 = 0.81, p < 0.001). We conclude that thigh angular acceleration is an important parameter when examining running performance across a range of speeds and the simple method introduced here to model αmax may have practical utility for future examinations into high-speed running mechanics.
An Insight into Anti-Inflammatory Activities and Inflammation Related Diseases of Anthocyanins: A Review of Both In Vivo and In Vitro Investigations

Anthocyanin is a type of flavonoid pigment widely present in fruits and vegetables. It can not only be used as natural pigment, but also has a variety of health functions, for instance, anti-oxidant, anti-inflammatory, anti-tumor, and neuroprotective activities. Persistent proinflammatory status is a major factor in the development, progression, and complications of chronic diseases. Not surprisingly, there are thus many food ingredients that can potentially affect inflammation related diseases and many studies have shown that anthocyanins play an important role in inflammatory pathways. In this paper, the inflammation related diseases (such as, obesity, diabetes, cardiovascular disease, and cancer) of anthocyanins are introduced, and the anti-inflammatory effect of anthocyanins is emphatically introduced. Moreover, the anti-inflammatory mechanism of anthocyanins is elaborated from the aspects of NF-κB, toll like receptor, MAPKs, NO, and ROS and the main efficacy of anthocyanins in inflammation and related diseases is determined. In conclusion, this review aims to get a clear insight into the role of anthocyanins in inflammation related diseases.
Raman Characterization of Fungal DHN and DOPA Melanin Biosynthesis Pathways

Fungal melanins represent a resource for important breakthroughs in industry and medicine, but the characterization of their composition, synthesis, and structure is not well understood. Raman spectroscopy is a powerful tool for the elucidation of molecular composition and structure. In this work, we characterize the Raman spectra of wild-type Aspergillus fumigatus and Cryptococcus neoformans and their melanin biosynthetic mutants and provide a rough “map” of the DHN (A. fumigatus) and DOPA (C. neoformans) melanin biosynthetic pathways. We compare this map to the Raman spectral data of Aspergillus nidulans wild-type and melanin biosynthetic mutants obtained from a previous study. We find that the fully polymerized A. nidulans melanin cannot be classified according to the DOPA pathway; nor can it be solely classified according to the DHN pathway, consistent with mutational analysis and chemical inhibition studies. Our approach points the way forward for an increased understanding of, and methodology for, investigating fungal melanins.
Daily Leucine Intake Is Positively Associated with Lower Limb Skeletal Muscle Mass and Strength in the Elderly

Higher daily protein intake, with an emphasis on leucine content, is thought to mitigate age-related anabolic resistance, potentially counteracting age-related morphological and functional declines. The present study investigated potential associations between total daily leucine intake and dependent variables, including quadriceps muscle cross-sectional area (CSA) and maximum dynamic muscle strength (1-RM) in a cohort of healthy free-living older individuals of both sexes (n = 67; 34/33 men/women). Participants performed three 24 h dietary recalls and underwent a magnetic resonance imaging exam followed by 1-RM tests. Our results demonstrate moderate associations between total daily leucine and both quadriceps CSA (r = 0.42; p = 0.004) and 1-RM (r = 0.45; p = 0.001). Furthermore, our exploratory biphasic linear regression analyses, adjusted for sex, age, and protein intake relative to body weight, revealed a plateau for daily leucine intake and muscle mass and muscle strength (~7.6–8.0 g·day−1) in older adults. In conclusion, we demonstrated that total daily leucine intake is associated with muscle mass and strength in healthy older individuals and this association remains after controlling for multiple factors, including overall protein intake. Furthermore, our breakpoint analysis revealed non-linearities and a potential threshold for habitual leucine intake, which may help guide future research on the effects of chronic leucine intake in age-related muscle loss.