Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Multiple Myeloma Using 5-Aza-2ʹ-Deoxycytidine and Bortezomib-Loaded Self-Assembling Nanoparticles

Purpose The aim of this study was to explore the use of self-assembling nanoparticles loaded with two chemotherapy drugs for the treatment of multiple myeloma. Materials and Methods Nanoparticle systems were developed based on amine polyethylene glycol-polycaprolactone (NH2-PEG-PCL) to encapsulate 5-Aza-2ʹ-deoxycytidine and Bortezomib using the self-assemble method. Morphological changes were observed by transmission electron microscopy (TEM), and the size, drug release, long-term stability, and release of reactive oxygen species (ROS) were analyzed. The MTT assay was used to evaluate the effects of drug-loaded nanoparticles (PEG-PCL-DAC-BTZ) in inhibiting the proliferation of multiple myeloma cells (U266 and LP-1), and the TUNEL assay and Western blotting were used to measure the induction of cell apoptosis. Results Based on the diameter of NH2-PEG-PCL and PEG-PCL-DAC-BTZ, the drug-loaded nanoparticles were successfully prepared. TEM revealed that PEG-PCL-DAC-BTZ was spherically shaped. More than 90% of the drugs were released after 72 h, and PEG-PCL-DAC-BTZ maintained a good stability. U266 and LP-1 cells treated with PEG-PCL-DAC-BTZ showed the highest growth inhibition, release of ROS, and cell apoptosis compared to those treated with unloaded nanoparticles and chemotherapy drugs alone. Conclusion The drug-loaded nanoparticles are a good foundation for the treatment of multiple myeloma as they showed a slow release profile, good stability, and superior anti-cancer effects in vitro.
Management of the Vertical Dimension in the Camouflage Treatment of an Adult Skeletal Class III Malocclusion

Treating skeletal class III malocclusions is one of the biggest challenges in Orthodontics. Given the complexity of these cases, orthognathic surgery is often the best treatment option. However, many patients refuse this treatment due to its risks, morbidity, and costs involved. Alternatively, dental compensation can be planned for some of these skeletal problems. This case report presents a dentoalveolar compensation in the orthodontic treatment of a 20-year-old female patient with class III malocclusion, concave profile, anterior crossbite, mandibular prognathism, maxillary retrusion, and a vertical deficiency in the posterior region. Treatment planning involved a multiloop edgewise archwire (MEAW) associated with intermaxillary elastics with counterclockwise rotation of the occlusal plane in the posterior region of the maxilla aiming at obtaining an increased posterior vertical dimension. After 24 months of treatment, the severe anterior crossbite was corrected, and the skeletal class III relationship was camouflaged. At the end of the orthodontic treatment, it was possible to observe an improved facial profile, a nice smile, and a functional occlusion. The results remained stable at a three-year follow-up. The MEAW, associated with the use of elastics, seems to be an effective treatment option for class III camouflage with reduced posterior vertical dimension with no need for additional anchoring devices but requiring adequate bending of wires and patient compliance.
In Vitro Antimicrobial and Antiproliferative Activities of the Root Bark Extract and Isolated Chemical Constituents of Zanthoxylum paracanthum Kokwaro (Rutaceae)

Zanthoxylum paracanthum Kokwaro (Rutaceae) is an endemic Kenyan and Tanzanian plant used in folk medicine by local populations. Although other Zanthoxylum species have been studied, only Z. paracantum stem extracts have been profiled, even though the roots are also used as herbal remedies. As root extracts may be another source of pharmaceutical compounds, the CH2Cl2/MeOH (1:1) root bark extract was studied in this report. Eight root bark compounds were isolated and their structural identities were confirmed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) (using COSY, HSQC, NOESY and HMBC) analyses. The structural identities were determined as follows: the fatty acid—myristic acid (1); the sterol—stigmasterol (2); the lignan—sesamin (3); two β-carboline alkaloids—10-methoxycanthin-6-one (6) and canthin-6-one (7); and three phenanthridine alkaloids—8-acetonyldihydrochelerythrine (4), arnottianamide (5) and 8-oxochelerythrine (8). Some of these compounds were identified in the species for the first time. These compounds and the extract were then tested in vitro against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 29213) and Candida albicans (ATCC 10231) before tests for antiproliferative activity against the human breast cancer (HCC 1395), human prostate cancer (DU 145) and normal (Vero E6) cell lines were conducted. Minimum inhibition concentration values of 3.91, 1.95, 0.98 and 7.81 µg/mL against MRSA, S. aureus, E. coli and C. albicans, respectively, were recorded. Among the isolates, canthin-6-one was the most active, followed by 10-methoxycanthin-6-one. The root extract and some of the compounds also had antiproliferative activity against the HCC 1395 cell line. Stigmasterol and canthin-6-one had IC50 values of 7.2 and 0.42. The root bark extract also showed activity, at 8.12 µg/mL, against the HCC 1395 cells. Out of the chemical isolates, 10-methoxycanthin-6-one and canthin-6-one showed the strongest inhibition of the DU 145 cells. The root extract had significant antimicrobial and antiproliferative activities, supporting the traditional use of this plant in treating microbial infections and cancer-related ailments.
Biomechanical study on the changes of stress in temporomandibular joints after the orthognathic surgery in patients with mandibular prognathism: a 3D finite element study.

PURPOSE This study aimed to analyze the changes of the stress distributions in TMJs for the pre- and postoperative patients with mandibular prognathism under unilateral occlusions, a frequent occlusion in mastication. METHODS Pre- and six-mouth postoperative cone-beam computed tomography images of thirteen patients diagnosed with mandibular prognathism were scanned and used to construct complete maxillofacial models, assigned as the Pre and Post group, respectively. Another ten asymptomatic individuals were defined as the Control group. The inhomogeneous properties were assigned to the models. The muscle forces and boundary conditions corresponding to left and right unilateral occlusions were applied on the models. The analysis of variation (ANOVA) was chosen for the comparison among the groups. RESULTS The results showed that the Pre group had abnormal stress distributions ang higher stress level in TMJs, compared with those of the Post and Control groups. Moreover, from clinical cases, symptoms of temporomandibular disorders (TMDs) always followed with increased stresses. CONCLUSION Generally, orthognathic surgeries could improve the stress distribution in TMJs of the patients with mandibular prognathism under the unilateral occlusions. However, the postoperative complications, especially symptoms of TMD, were closely related to changes of stress for patients with mandibular prognathism after orthognathic surgeries. Individual virtual surgery and finite element analysis should be conducted to prevent complications in TMJ.
Conceptual comparison of metabolic pathways with electronic circuits

An electronic circuit has been designed to mimic glycolysis, the Citric Acid (TCA) cycle and the electron transport chain. Enzymes play a vital role in metabolic pathways; similarly transistors play a vital role in electronic circuits; the characteristics of enzymes in comparison with those of transistors suggests that the properties are analagous. Enzymes possess an active site into which the substrate binds, similarly the transistor possess a layer in which the recombination of holes and electrons takes place. Hence the applied voltage in the circuit is considered as the substrate. The enthalpy values of the enzymes are converted into volts, which is to be applied to the circuit. ATP is the energy source in the metabolic pathway which functions like a potential in the electronic circuit. Some enzymes can function only with the help of a cofactor; here modelled as a switch. Using all the above electronic circuit analogues, which possess the similar characteristics of the metabolic pathway constituents, circuits have been designed.
Morphology of Tissue Disruption at Sites of High-Grade Tumors

Background Invasive solid cancers originating from diverse organs like breast, ovary and lung metastasize to distant sites. The structural changes at the primary sites of these high-grade tumors have not been well characterized. The main aim of the current study was to examine if there is any morphological overlap of metastasizing tissues of different invasive tumors. Methods Whole slide hematoxylin and eosin (H&E) stained images from web repository of multiple tumor specimens were used for this study. ImageJ was used for image processing and analyses. Results The metastatic tissue(s) at the primary sites of different examined high-grade tumors appeared similar, irrespective of organ of origin of the primary tumor. Numerous excrescences with the repetitive appearance of a bulb-like projection with a narrowed-off trailing end were seen emanating from the tumor cell membrane. Many of them contained nuclei, while others were empty vesicles. Although these structures were not exactly equal in their dimensions, the rubrics of architectural distortion in different high-grade tumors were conserved. Conclusions The preliminary observations suggest for the first time that there is structural similarity of the epithelial dysmorphia in many high-grade invasive tumors, irrespective of their parental tissue of origin. This commonality of morphological prints of metastases suggests that similar pathways of cytosolic force generation are activated during temporal progression of cancer, resulting in the conserved mushroom-shaped appearance of the dismantling individual cell or cell clusters from the parental epithelium. The conserved genomic mechanisms underlying these fascinating observations merit testing and validation in future studies.
Hybrid Hydrogels for Synergistic Periodontal Antibacterial Treatment with Sustained Drug Release and NIR-Responsive Photothermal Effect

Background Periodontal pathogenic bacteria promote the destruction of periodontal tissues and cause loosening and loss of teeth in adults. However, complete removal of periodontal pathogenic bacteria, at both the bottom of the periodontal pocket and the root bifurcation area, remains challenging. In this work, we explored a synergistic antibiotic and photothermal treatment, which is considered an alternative strategy for highly efficient periodontal antibacterial therapy. Methods Mesoporous silica (MSNs) on the surface of Au nanobipyramids (Au NBPs) were designed to achieve the sustained release of the drug and photothermal antibacterials. The mesoporous silica-coated Au NBPs (Au NBPs@SiO2) were mixed with gelatin methacrylate (GelMA-Au NBPs@SiO2). Au NBPs@SiO2 and GelMA-Au NBPs@SiO2 hybrid hydrogels were characterized, and the drug content and photothermal properties in terms of the release profile, bacterial inhibition, and cell growth were investigated. Results The GelMA-Au NBPs@SiO2 hybrid hydrogels showed controllable minocycline delivery, and the drug release rates increased under 808 nm near-infrared (NIR) light irradiation. The hydrogels also exhibited excellent antibacterial properties, and the antibacterial efficacy of the antibiotic and photothermal treatment was as high as 90% and 66.7% against Porphyromonas gingivalis (P. gingivalis), respectively. Moreover, regardless of NIR irradiation, cell viability was over 80% and the concentration of Au NBPs@SiO2 in the hybrid hydrogels was as high as 100 µg/mL. Conclusion We designed a new near-infrared light (NIR)-activated hybrid hydrogel that offers both sustained release of antibacterial drugs and photothermal treatment. Such sustained release pattern yields the potential to rapidly eliminate periodontal pathogens in the periodontal pocket, and the photothermal treatment maintains low bacterial retention after the drug treatment.
Phytoremediation of Cadmium: Physiological, Biochemical, and Molecular Mechanisms

Cadmium (Cd) is one of the most toxic metals in the environment, and has noxious effects on plant growth and production. Cd-accumulating plants showed reduced growth and productivity. Therefore, remediation of this non-essential and toxic pollutant is a prerequisite. Plant-based phytoremediation methodology is considered as one a secure, environmentally friendly, and cost-effective approach for toxic metal remediation. Phytoremediating plants transport and accumulate Cd inside their roots, shoots, leaves, and vacuoles. Phytoremediation of Cd-contaminated sites through hyperaccumulator plants proves a ground-breaking and profitable choice to combat the contaminants. Moreover, the efficiency of Cd phytoremediation and Cd bioavailability can be improved by using plant growth-promoting bacteria (PGPB). Emerging modern molecular technologies have augmented our insight into the metabolic processes involved in Cd tolerance in regular cultivated crops and hyperaccumulator plants. Plants’ development via genetic engineering tools, like enhanced metal uptake, metal transport, Cd accumulation, and the overall Cd tolerance, unlocks new directions for phytoremediation. In this review, we outline the physiological, biochemical, and molecular mechanisms involved in Cd phytoremediation. Further, a focus on the potential of omics and genetic engineering strategies has been documented for the efficient remediation of a Cd-contaminated environment.
Tumor-Associated Macrophage Status in Cancer Treatment

Tumor-associated macrophages (TAMs) represent the most abundant innate immune cells in tumors. TAMs, exhibiting anti-inflammatory phenotype, are key players in cancer progression, metastasis and resistance to therapy. A high TAM infiltration is generally associated with poor prognosis, but macrophages are highly plastic cells that can adopt either proinflammatory/antitumor or anti-inflammatory/protumor features in response to tumor microenvironment stimuli. In the context of cancer therapy, many anticancer therapeutics, apart from their direct effect on tumor cells, display different effects on TAM activation status and density. In this review, we aim to evaluate the indirect effects of anticancer therapies in the modulation of TAM phenotypes and pro/antitumor activity.
Synergistic Effect between Usnic Acid and Polymyxin B against Resistant Clinical Isolates of Pseudomonas aeruginosa

The present study aimed to characterize the susceptibility profile of Pseudomonas aeruginosa and Acinetobacter spp. clinical isolates to polymyxin B in a public hospital in Recife-PE, Brazil, between the years of 2018 and 2019, as well as to search for the presence of the mcr-1 gene and evaluate the interaction between polymyxin B and usnic acid against these isolates. The strains were identified using the BD Phoenix™ automated system and the agar-spot test was used to determine the susceptibility profile to polymyxin B. The minimum inhibitory concentrations (MICs) of usnic acid and polymyxin B were determined through the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI). Subsequently, Polymerase Chain Reaction (PCR) was performed to detect the mcr-1 gene in the isolates. The interaction between usnic acid and polymyxin B was evaluated by the Checkerboard assay. Among 34 isolates of P. aeruginosa, 26.5% (9/34) were positive for the polymyxin B agar-spot test, and 11.8% (4/34) presented an intermediate susceptibility (MIC = 4 μg/mL), while 14.7% (5/34) presented antimicrobial resistance with MIC values ranging from 8 to 32 μg/mL. Among 38 isolates of Acinetobacter spp. , 13.2% (5/38) were positive for the polymyxin B agar-spot test and all of them were resistant to polymyxin B with a MIC value > 32 μg/mL. The mcr-1 gene was not detected in the clinical isolates. Regarding usnic acid, it presented a moderate antibacterial activity against two P. aeruginosa isolates (MIC = 250 μg/mL) and no activity was detected against the others. A synergistic effect between usnic acid and polymyxin B was observed against three clinical isolates of P. aeruginosa which were resistant to polymyxin B (FICI ≤ 0.5). Therefore, it was possible to observe that usnic acid is a promising candidate to be used in combination with polymyxin B against infections caused by resistant P. aeruginosa.
Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1β and IL-18 in the Septic Response

Pyroptosis, an inflammatory form of programmed cell death, is the initiating event of sepsis and results in immune imbalance by releasing IL-1β and IL-18 in the early stages. Studies show that enhancing autophagy via genetic manipulation can inhibit pyroptosis and prolong the survival of a sepsis animal model, indicating a possible therapeutic strategy against sepsis. However, almost no study so far has achieved pyroptosis inhibition via pharmacological autophagy induction in a sepsis disease model. To this end, we established an in vitro sepsis model by stimulating primary human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS), and analyzed the effect of the autophagy agonist rapamycin (RAPA) on pyroptosis. Phorbol 12-myristate 13-acetate- (PMA-) activated human THP-1 cells were used as the positive control. LPS significantly increased the levels of the pyroptotic protein Gasdermin D (GSDMD), cysteinyl aspartate-specific proteinase 1 (caspase-1), secreted LDH, IL-1β, and IL-18. RAPA treatment downregulated the above factors and enhanced autophagy in the LPS-stimulated HUVECs and THP-1 cells. This study shows that RAPA abrogates LPS-mediated increase in IL-1β and IL-18 by inhibiting pyroptosis and enhancing autophagy.
Gender Differences in Cardiac Function Following Three-Month Administration of Tofogliflozin in Patients With Diabetes Mellitus

Background Patients with type 2 diabetes mellitus (T2DM) are at increased risk for impairment in heart failure and diastolic relaxation while preserving ejection fraction (EF). Recently, several sodium glucose cotransporter-2 (SGLT2) inhibitors have demonstrated to decrease cardiovascular disease (CVD) events in elderly diabetic patients, although gender difference in the effect of SGLT2 inhibitors is unknown. The objective of the present study was to evaluate gender difference in the effect of tofogliflozin, one of the SGLT2 inhibitors, on CVD function in patients with diabetes mellitus. Methods This was a retrospective study. Patients received 20 mg of tofogliflozin daily for 3 months. EF, ratio of early filling to atrial filling (E/A), a change in mitral inflow E and mitral e' annular velocities (E/e'), left atrial dimension (LAD) and maximal diameter of inferior vena cava (IVCmax), including various physiological parameters were measured between baseline, 1 month and 3 months after administration of tofogliflozin. Interaction between gender and time after administration was evaluated using mixed effect model. Results The results showed significant decrease in E/e' (P < 0.01) and significant interaction between time and gender in E/A (P < 0.01), following administration of tofogliflozin for 3 months. EF was constantly higher significantly in women (P < 0.01). Conclusion It is concluded that 3-month administration of tofogliflozin decreased E/e' with gender difference in EF and E/A.
Novel Biocompatible Polysaccharide-Based Eutectogels with Tunable Rheological, Thermal, and Mechanical Properties: The Role of Water

The natural deep eutectic solvent (NADES) is an excellent solvent for insoluble natural products and medicines. Eutectogels formed by gelation of NADESs are interesting materials that deserve attention. In this study, xanthan gum was used as a gelator to gel choline chloride-xylitol with different water contents in virtue of the excellent solubility of choline chloride-xylitol (1:1) to quercetin. We observed that water was critical to the formation of eutectogels. An MTT assay indicated that our eutectogel had excellent biocompatibility as its corresponding hydrogel. According to rheological tests, xanthan gum-based eutectogels had better viscoelastic properties, higher thermal stability, and more defined shear thinning behavior than its corresponding hydrogel. Texture profile analysis showed that eutectogels with less water content had higher hardness and adhesiveness. Meanwhile, Differential scanning calorimeter (DSC) results suggested that the various rheological and texture properties of eutectogels could be attributed to changes in the water state, which was influenced by the hydrogen bonding network of NADES. This biocompatible eutectogel with tunable properties was expected to find applications in novel drug delivery vehicles, which are widely used in the fields of medicine and food.
Selenium Protects against Zearalenone-Induced Oxidative Stress and Apoptosis in the Mouse Kidney by Inhibiting Endoplasmic Reticulum Stress

This study assessed the molecular mechanism of selenium (Se) protecting against kidney injury induced by zearalenone (ZEA) in mice. The experimental mice were divided into 4 groups including the control group, the Se group, the ZEA group, and the Se+ZEA group; ZEA and Se were administered orally for 28 days. The changes in renal biochemical index (BUN, UA, and CRE), biochemical change of kidney damage such as BUN, UA, and CRE, and oxidative damage such as MDA, T-SOD, and GSH-Px were investigated. Pathological sections and TUNEL staining were used to analyze renal pathological changes and cell apoptosis. qRT-PCR and Western blot were employed to detect the expression of genes and proteins which were related with endoplasmic reticulum stress. The results showed that ZEA increased the concentration of BUN, UA, and CRE and the content of MDA and decreased the activities of T-SOD and GSH-Px in the mouse kidneys. However, Se reversed above changes of the biochemical and antioxidant indexes of renal injury. Moreover, the results also showed that ZEA can increase the expression of Bax, caspase-12, caspase-3, Bip, CHOP, JNK protein, and mRNA and decrease the expression of Bcl-2 protein and mRNA. But Se reversed these proteins and genes related to endoplasmic reticulum stress and apoptosis. It can be concluded that Se protected against the kidney damage induced by ZEA. Se may protect the kidney from ZEA-induced apoptosis and oxidative stress by inhibiting ERS.