Revealing the diversity of Jojoba-associated fungi using amplicon metagenome approach and assessing the in vitro biocontrol activity of its cultivable community.

Jojoba shrubs are wild plants cultivated in arid and semiarid lands and characterized by tolerance to drought, salinity, and high temperatures. Fungi associated with such plants may be attributed to the tolerance of host plants against biotic stress in addition to the promotion of plant growth. Previous studies showed the importance of jojoba as jojoba oil in the agricultural field; however, no prior study discussed the role of jojoba-associated fungi (JAF) in reflecting plant health and the possibility of using JAF in biocontrol. Here, the culture-independent and culture-dependent approaches were performed to study the diversity of the jojoba-associated fungi. Then, the cultivable fungi were evaluated for in-vitro antagonistic activity and in vitro plant growth promotion assays. The metagenome analysis revealed the existence of four fungal phyla: Ascomycota, Aphelidiomycota, Basidiomycota, and Mortierellomycota. The phylum Ascomycota was the most common and had the highest relative abundance in soil, root, branch, and fruit samples (59.7%, 50.7%, 49.8%, and 52.4%, respectively). Alternaria was the most abundant genus in aboveground tissues: branch (43.7%) and fruit (32.1%), while the genus Discosia had the highest abundance in the underground samples: soil (24%) and root (30.7%). For the culture-dependent method, a total of 14 fungi were isolated, identified, and screened for their chitinolytic and antagonist activity against three phytopathogenic fungi (Fusarium oxysporum, Alternaria alternata and Rhizoctonia solani) as well as their in vitro plant growth promotion (PGP) activity. Based on ITS sequence analysis, the selected potent isolates were identified as Aspergillus stellatusEJ-JFF3, Aspergillus flavus EJ-JFF4, Stilbocrea sp. EJ-JLF1, Fusarium solani EJ-JRF3, and Amesia atrobrunneaEJ-JSF4. The endophyte strain A. flavus EJ-JFF4 exhibited the highest chitinolytic activity (9 Enzyme Index) and antagonistic potential against Fusarium oxysporum, Alternaria alternata, and Rhizoctonia solani phytopathogens with inhibitory percentages of 72, 70, and 80 respectively. Also, A. flavus EJ-JFF4 had significant multiple PGP properties, including siderophore production (69.3%), phosphate solubilization (95.4 µg ml-1). The greatest production of Indol-3-Acetic Acid was belonged to A. atrobrunnea EJ-JSF4 (114.5 µg ml-1). The analysis of FUNGuild revealed the abundance of symbiotrophs over other trophic modes, and the guild of endophytes was commonly assigned in all samples. For the first time, this study uncovered fungal diversity associated with jojoba plants using a culture-independent approach and in-vitro assessed the roles of cultivable fungal strains in promoting plant growth and biocontrol. The present study indicated the significance of jojoba shrubs as a potential source of diverse fungi with high biocontrol and PGP activities.

Phytochemical and biological assessment of secondary metabolites isolated from a rhizosphere strain, Sphingomonas sanguinis DM of Datura metel.

BACKGROUND: The plant roots excrete a large number of organic compounds into the soil. The rhizosphere, a thin soil zone around the roots, is a hotspot for microbial activity, making it a crucial component of the soil ecosystem. Secondary metabolites produced by rhizospheric Sphingomonas sanguinis DM have sparked significant curiosity in investigating their possible biological impacts. METHODS: A bacterial strain has been isolated from the rhizosphere of Datura metel. The bacterium's identification, fermentation, and working up have been outlined. The ethyl acetate fraction of the propagated culture media of Sphingomonas sanguinis DM was fractioned and purified using various chromatographic techniques. The characterization of the isolated compounds was accomplished through the utilization of various spectroscopic techniques, such as UV, MS, 1D, and 2D-NMR. Furthermore, the evaluation of their antimicrobial activity was conducted using the agar well diffusion method, while cytotoxicity was assessed using the MTT test. RESULTS: The extract from Sphingomonas sanguinis DM provided two distinct compounds: n-dibutyl phthalic acid (1) and Bis (2-methyl heptyl) phthalate (2) within its ethyl acetate fraction. Furthermore, the 16S rRNA gene sequence of Sphingomonas sanguinis DM has been registered under the NCBI GenBank database with the accession number PP422198. The bacterial extract exhibited its effect against gram-positive bacteria, inhibiting Streptococcus mutans (12.6 ± 0.6 mm) and Staphylococcus aureus (10.6 ± 0.6 mm) compared to standard antibiotics. Conversely, compound 1 showed a considerable effect against phytopathogenic fungi such as Alternaria alternate (56.3 ± 10.6 mm) and Fusarium oxysporum (21.3 ± 1.5 mm) with a MIC value of 17.5 µg/mL. However, it was slightly active against Klebsiella pneumonia (11.0 ± 1.0 mm). Furthermore, compound 2 was the most active metabolite, having a significant antimicrobial efficacy against Rhizoctonia solani (63.6 ± 1.1 mm), Pseudomonas aeruginosa (16.7 ± 0.6 mm), and Alternaria alternate (20.3 ± 0.6 mm) with MIC value at 15 µg/mL. In addition, compound 2 exhibited the most potency against hepatocellular (HepG-2) and skin (A-431) carcinoma cell lines with IC50 values of 107.16 µg/mL and 111.36 µg/mL, respectively. CONCLUSION: Sphingomonas sanguinis DM, a rhizosphere bacterium of Datura metel, was studied for its phytochemical and biological characteristics, resulting in the identification of two compounds with moderate antimicrobial and cytotoxic activities.

Neuroprotective activity of Colocasia esculenta (L.) Schott leaves against monosodium glutamate-induced excitotoxicity in rats: phytochemical and molecular docking study.

Colocasia esculenta (L.) Schott is a food crop with long history of use in treatment of various disorders including neurological diseases. The methanolic leaves extract (ME) and its n-butanol fraction (n-BF) demonstrated significant in vivo neuroprotective activity in monosodium glutamate induced excitotoxicity in rats. Sixteen and fifteen polyphenolic compounds were identified in n-BF and ME, respectively, using HPLC. Phytochemical investigation of n-BF followed by 1D (1H and 13C NMR) spectroscopic analyses led to isolation and identification of daucosterol (1), thermopsoside (2) and chrysoeriol 7-O-ß-D-neohesperidoside (3) for the first time from genus Colocasia, in addition to orientin (4). LC/MS/MRM analysis of fraction V obtained from n-BF revealed identification of 13 polyphenolic compounds. Molecular docking of isolated compounds confirmed binding of all compounds at the target pocket with higher energy than crystallised ligand. The current study evaluated and confirmed the mechanistic aspects of neuroprotective activity of C. esculenta leaves for the first time.

Biobran-loaded core/shell nanofibrous scaffold: a promising wound dressing candidate.

This research examined the effectiveness of Biobran as a bioactive substance that could potentially improve wound healing. It also looked at how Biobran affects the properties of a nanofibrous scaffold made through coaxial electrospinning. This is the first study exploring the use of Biobran in this context and its interaction with nanofibrous scaffolds. The scaffolds were composed of poly(ε-caprolactone) (PCL) in the shell and various concentrations of Biobran blended with polyvinyl alcohol (PVA) in the core. The properties of the scaffolds were characterized by SEM, TEM, FTIR, XRD, TGA, DSC, stress-strain test, WCA, release test, MTT cytotoxicity assay, wound scratching assay, and the dye exclusion method using trypan blue. The scaffolds loaded with Biobran exhibited a more compact and smooth morphology compared with the scaffold without Biobran. The physical interaction and crystallinity of the polymers in the scaffolds were also affected by Biobran in a concentration-dependent manner. This positively influenced their tensile strength, elongation at break, thermal stability, and hydrophilicity. The porosity, water uptake capacity, and WVTR of the nanofibrous scaffolds are within the optimal ranges for wound healing. The release rate of Biobran, which revealed a biphasic release pattern, decreased with increasing Biobran concentration, resulting in controlled and sustained delivery of Biobran from the nanofiber scaffolds. The cell viability assays showed a dose-dependent effect of Biobran on WISH cells, which might be attributed to the positive effect of Biobran on the physicochemical properties of the nanofibrous scaffolds. These findings suggest that Biobran-loaded core/shell nanofiber scaffolds have a potential application in wound healing as an ideal multifunctional wound dressing.

Treatment of intramedullary spinal cord tumors: a modified Delphi technique of the North American Spine Society Section of Spine Oncology.

OBJECTIVE: Intramedullary spinal cord tumors (IMSCTs) are rare tumors with heterogeneous presentations and natural histories that complicate their management. Standardized guidelines are lacking on when to surgically intervene and the appropriate aggressiveness of resection, especially given the risk of new neurological deficits following resection of infiltrative tumors. Here, the authors present the results of a modified Delphi method using input from surgeons experienced with IMSCT removal to construct a framework for the operative management of IMSCTs based on the clinical, radiographic, and tumor-specific characteristics. METHODS: A modified Delphi technique was conducted using a group of 14 neurosurgeons experienced in IMSCT resection. Three rounds of written correspondence, surveys, and videoconferencing were carried out. Participants were queried about clinical and radiographic criteria used to determine operative candidacy and guide decision-making. Members then completed a final survey indicating their choice of observation or surgery, choice of resection strategy, and decision to perform duraplasty, in response to a set of patient- and tumor-specific characteristics. Consensus was defined as ≥ 80% agreement, while responses with 70%-79% agreement were defined as agreement. RESULTS: Thirty-six total characteristics were assessed. There was consensus favoring surgical intervention for patients with new-onset myelopathy (86% agreement), chronic myelopathy (86%), or progression from mild to disabling numbness (86%), but disagreement for patients with mild numbness or chronic paraplegia. Age was not a determinant of operative candidacy except among frail patients, who were deemed more suitable for observation (93%). Well-circumscribed (93%) or posteriorly located tumors reaching the surface (86%) were consensus surgical lesions, and participants agreed that the presence of syringomyelia (71%) and peritumoral T2 signal change (79%) were favorable indications for surgery. There was consensus that complete loss of transcranial motor evoked potentials with a 50% decrease in the D-wave amplitude should halt further resection (93%). Preoperative symptoms seldom influenced choice of resection strategy, while a distinct cleavage plane (100%) or visible tumor-cord margins (100%) strongly favored gross-total resection. CONCLUSIONS: The authors present a modified Delphi technique highlighting areas of consensus and agreement regarding surgical management of IMSCTs. Although not intended as a substitute for individual clinical decision-making, the results can help guide care of these patients. Additionally, areas of controversy meriting further investigation are highlighted.

Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction.

Therapeutic angiogenesis represents a promising avenue to revascularize the ischemic heart. Its limited success is partly due to our poor understanding of the cardiac stroma, specifically mural cells, and their response to ischemic injury. Here, we combine single-cell and positional transcriptomics to assess the behavior of mural cells within the healing heart. In response to myocardial infarction, mural cells adopt an altered state closely associated with the infarct and retain a distinct lineage from fibroblasts. This response is concurrent with vascular rarefaction and reduced vascular coverage by mural cells. Positional transcriptomics reveals that the infarcted heart is governed by regional-dependent and temporally regulated programs. While the remote zone acts as an important source of pro-angiogenic signals, the infarct zone is accentuated by chronic activation of anti-angiogenic, pro-fibrotic, and inflammatory cues. Together, our work unveils the spatiotemporal programs underlying cardiac repair and establishes an association between vascular deterioration and mural cell dysfunction.

Partial sternectomy with reconstruction of a giant cell tumor of the sternum, a case report, Saudi, Arabia.

BACKGROUND: Giant cell tumor (GCT) is a relatively common and locally aggressive benign bone tumor that rarely affects the sternum. CASE PRESENTATION: We report a case of giant cell tumor of the sternum in a 28-year-old Saudi with painful swelling at the lower part of the sternum. Subtotal sternectomy and reconstruction with a neosternum using two layers of proline mesh, a methyl methacrylate prosthesis, and bilateral pectoralis muscle advancement flaps were performed. CONCLUSIONS: Giant cell tumor of the sternum is a rare diagnosis. Surgical resection with negative margins is the ideal management. To avoid defects or instability of the chest wall, reconstruction of the chest wall with neosternum should be considered.

Development of carboxymethyl cellulose-graphene oxide biobased composite for the removal of methylene blue cationic dye model contaminate from wastewater.

Utilizing Glutaraldehyde crosslinked sodium carboxymethyl cellulose (CMC-GA) hydrogel and its nanographene oxide composite (CMC-GA-GOx), an effective carboxymethyl cellulose-graphene oxide biobased composites adsorbent was developed for the adsorption removal of methylene blue (MB) cationic dye contaminate from industrial wastewater. The CMC-GA-GOx composites developed were characterized using FTIR, RAMAN, TGA, SEM, and EDX analysis instruments. Through batch experiments, several variables affecting the removal of MB dye, including the biocomposites GO:CMC composition, adsorption time, pH and temperature, initial MB concentration, adsorbent dosage, and NaCl concentration, were investigated under different conditions. The maximum dye removal percentages ranged between 93 and 98%. They were obtained using biocomposites CMC-GA-GO102 with 20% GO weight percent, adsorption time 25 min, adsorption temperature 25 °C, MB concentrations 10-30 ppm, adsorption pH 7.0, and 0.2 g adsorbent dose. The experimental data of the adsorption process suit the Langmuir isotherm more closely with a maximal monolayer adsorption capacity of 76.92 mg/g. The adsorption process followed the kinetic model of pseudo-second order. The removal of MB was exothermic and spontaneous from a thermodynamic standpoint. In addition, thermodynamic results demonstrated that adsorption operates most effectively at low temperatures. Finally, the reusability of the developed CMC-GA-GO102 has been proved through 10 successive cycles where only 14% of the MB dye removal percentage was lost. These results suggest that the developed CMC-GA-GO102 composite may be an inexpensive and reusable adsorbent for removing organic cationic dyes from industrial wastewater.

Antimicrobial, antiproliferative activities and molecular docking of metabolites from Alternaria alternata.

Endophytic fungi allied to plants have sparked substantial promise in discovering new bioactive compounds. In this study, propagation of the endophytic fungus Alternaria alternata HE11 obtained from Colocasia esculanta leaves led to the isolation of Ergosterol (1), ß-Sitosterol (2), Ergosterol peroxide (3), in addition to three dimeric naphtho-γ-pyrones, namely Fonsecinone A (4), Asperpyrone C (5), and Asperpyrone B (6), which were isolated from genus Alternaria for the first time. Structures of the isolated compounds were established on the basis of extensive 1D and 2D NMR and, MS measurements. The ethyl acetate extract, as well as compounds 1, 3, 4 and 6 were evaluated for their antimicrobial activity using agar well-diffusion and broth microdilution assays. Molecular docking study was carried out to explore the pharmacophoric moieties that governed the binding orientation of antibacterial active compounds to multidrug efflux transporter AcrB and the ATP binding site to E. coli DNA gyrase using MOE software. Results revealed that the most active antibacterial compounds 4 and 6 bind with high affinity in the phenylalanine-rich cage and are surrounded with other hydrophobic residues. The antiproliferative activity of all isolated compounds was in vitro evaluated using the human prostatic adenocarcinoma cell lines DU-145, PC-3, PC-3 M, 22Rv1 and CWR-R1ca adopting MTT assay. Compound 4 was the most active against almost all tested cell lines, with IC50 values 28.6, 21.6, 17.1 and 13.3 against PC-3, PC-3 M, 22Rv1 and CWR-R1ca cell lines, respectively.

Topically Applied Biopolymer-Based Tri-Layered Hierarchically Structured Nanofibrous Scaffold with a Self-Pumping Effect for Accelerated Full-Thickness Wound Healing in a Rat Model.

Wound healing has grown to be a significant problem at a global scale. The lack of multifunctionality in most wound dressing-based biopolymers prevents them from meeting all clinical requirements. Therefore, a multifunctional biopolymer-based tri-layered hierarchically nanofibrous scaffold in wound dressing can contribute to skin regeneration. In this study, a multifunctional antibacterial biopolymer-based tri-layered hierarchically nanofibrous scaffold comprising three layers was constructed. The bottom and the top layers contain hydrophilic silk fibroin (SF) and fish skin collagen (COL), respectively, for accelerated healing, interspersed with a middle layer of hydrophobic poly-3-hydroxybutyrate (PHB) containing amoxicillin (AMX) as an antibacterial drug. The advantageous physicochemical properties of the nanofibrous scaffold were estimated by SEM, FTIR, fluid uptake, contact angle, porosity, and mechanical properties. Moreover, the in vitro cytotoxicity and cell healing were assessed by MTT assay and the cell scratching method, respectively, and revealed excellent biocompatibility. The nanofibrous scaffold exhibited significant antimicrobial activity against multiple pathogenic bacteria. Furthermore, the in vivo wound healing and histological studies demonstrated complete wound healing in wounded rats on day 14, along with an increase in the expression level of the transforming growth factor-ß1 (TGF-ß1) and a decrease in the expression level of interleukin-6 (IL-6). The results revealed that the fabricated nanofibrous scaffold is a potent wound dressing scaffold, and significantly accelerates full-thickness wound healing in a rat model.

The ARISCAT Risk Index as a Predictor of Pulmonary Complications After Thoracic Surgeries, Almoosa Specialist Hospital, Saudi Arabia.

Background: Pulmonary complications after thoracic surgery are common and are associated with prolonged hospital stay, higher costs, and increased mortality. This study aimed to evaluate the value of The Assess Respiratory risk in Surgical Patients in Catalonia (ARISCAT) risk index in predicting pulmonary complications after thoracic surgery. Methods: This retrospective study was conducted at Almoosa Specialist Hospital, Saudi Arabia, from August 2016 to August 2019 and included 108 patients who underwent thoracic surgery during the study period. Demographic data, ARISCAT risk index score, length of hospital stay, time of chest tube removal, postoperative complications, and time of discharge were recorded. Results: The study involved 108 patients who met the inclusion criteria. Their mean age was 42.5 ± 18.9 years, and most of them were men (67.6%). Comorbid diseases were present in 53.7%, including mainly type 2 diabetes mellitus and hypertension. FEV1% was measured in 58 patients, with a mean of 71.1 ± 7.3%. The mean ARISCAT score was 39.3 ± 12.4 and ranged from 24 to 76, with more than one-third (35.2%) having a high score grade. The most common surgical procedures were thoracotomy in 47.2%, video-assisted thoracoscopic surgery (VATS) in 28.7%, and mediastinoscopy in 17.6%. Postoperative pulmonary complications (PPCs) occurred in 22 patients (20.4%), mainly pneumonia and atelectasis (9.2%). PPCs occurred most frequently during thoracotomy (68.2%), followed by VATS (13.6%), and mediastinoscopy (9.1%). Multinomial logistic regression of significant risk factors showed that lower FEV1% (OR = 0.88 [0.79-0.98]; p=0.017), longer ICU length of stay (OR = 1.53 [1.04-2.25]; p=0.033), a higher ARISCAT score (OR = 1.22 [1.02-1.47]; p=0.040), and a high ARISCAT grade (OR = 2.77 [1.06-7.21]; p=0.037) were significant predictors of the occurrence of postoperative complications. Conclusion: ARISCAT scoring system, lower FEV1% score, and longer ICU stay were significant predictors of postoperative complications. In addition, thoracotomy was also found to be associated with PPCs.

One-pot facile synthesis of hexagonal Bi2Te3 nanosheets and its novel nanocomposites: Characterization, anticancer, antibacterial, and antioxidant activities.

Bismuth Telluride (Bi2Te3) layered structure results in extraordinary features in diagnostic and therapeutic applications. However, Bi2Te3 synthesis with reliable stability and biocompatibility in biological systems was the major challenge that limited its biological application. Herein, reduced graphene oxide (RGO) or graphitic carbon nitride (CN) nanosheets were incorporated into Bi2Te3 matrix to improve exfoliation. Bi2Te3 nanoparticles (NPs) and its novel nanocomposites (NCs): CN@Bi2Te3 and CN-RGO@Bi2Te3 were solvothermally synthesized, physiochemically characterized and assessed for their anticancer, antioxidant, and antibacterial activities. X-ray diffraction depicted Bi2Te3 rhombohedral lattice structure. Fourier-transform infrared and Raman spectra confirmed NC formation. Scanning and transmission electron microscopy revealed 13 nm thickness and 400-600 nm diameter of hexagonal, binary, and ternary nanosheets of Bi2Te3-NPs/NCs. Energy dispersive X-ray Spectroscopy revealed the presence of Bi, Te, and carbon atoms in the tested NPs with negatively charged surfaces as depicted by zeta sizer. CN-RGO@Bi2Te3-NC displayed the smallest nanodiameter (359.7 nm) with the highest Brunauer-Emmett-Teller surface area and antiproliferative activity against MCF-7, HepG2 and Caco-2. Bi2Te3-NPs had the greatest scavenging activity (96.13 ± 0.4%) compared to the NCs. The NPs inhibitory activity was greater against Gram-negative bacteria than that of Gram-positive bacteria. Integration of RGO and CN with Bi2Te3-NPs enhanced their physicochemical properties and therapeutic activities giving rise to their promising capacity for future biomedical applications.

Spatial compartmentalization of signaling imparts source-specific functions on secreted factors.

Efficient regeneration requires multiple cell types acting in coordination. To better understand the intercellular networks involved and how they change when regeneration fails, we profile the transcriptome of hematopoietic, stromal, myogenic, and endothelial cells over 14 days following acute muscle damage. We generate a time-resolved computational model of interactions and identify VEGFA-driven endothelial engagement as a key differentiating feature in models of successful and failed regeneration. In addition, the analysis highlights that the majority of secreted signals, including VEGFA, are simultaneously produced by multiple cell types. To test whether the cellular source of a factor determines its function, we delete VEGFA from two cell types residing in close proximity: stromal and myogenic progenitors. By comparing responses to different types of damage, we find that myogenic and stromal VEGFA have distinct functions in regeneration. This suggests that spatial compartmentalization of signaling plays a key role in intercellular communication networks.

A Novel P@SiO2 Nano-Composite as Effective Adsorbent to Remove Methylene Blue Dye from Aqueous Media.

This work aims to prepare a novel phosphate-embedded silica nanoparticles (P@SiO2) nanocomposite as an effective adsorbent through a hydrothermal route. Firstly, a mixed solution of sodium silicate and sodium phosphate was passed through a strong acidic resin to convert it into hydrogen form. After that, the resultant solution was hydrothermally treated to yield P@SiO2 nanocomposite. Using kinetic studies, methylene blue (MB) dye was selected to study the removal behavior of the P@SiO2 nanocomposite. The obtained composite was characterized using several advanced techniques. The experimental results showed rapid kinetic adsorption where the equilibrium was reached within 100 s, and the pseudo-second-order fitted well with experimental data. Moreover, according to Langmuir, one gram of P@SiO2 nanocomposite can remove 76.92 mg of the methylene blue dye. The thermodynamic studies showed that the adsorption process was spontaneous, exothermic, and ordered at the solid/solution interface. Finally, the results indicated that the presence of NaCl did not impact the adsorption behavior of MB dye. Due to the significant efficiency and promising properties of the prepared P@SiO2 nanocomposite, it could be used as an effective adsorbent material to remove various cationic forms of pollutants from aqueous solutions in future works.

Nephroprotective effect of Physalis peruviana L. calyx extract and its butanolic fraction against cadmium chloride toxicity in rats and molecular docking of isolated compounds.

BACKGROUND: Cadmium is an environmentally toxic metal that has deleterious effects on both animals and humans due to its accumulation in different body tissues. Physalis peruviana L. fruit and calyx contain many active constituents which are used traditionally for their different biological activities. Based on the traditional uses of P. peruviana L. calyx, we aimed to evaluate the nephroprotective effect of their 80% aqueous methanol extract (AME) and n-butanol fraction (Bu.F.) against cadmium chloride-induced nephrotoxicity in rats and to correlate this activity with phytoconstituents isolated using molecular docking studies. METHODS: The n-butanol fraction of P. peruviana L. calyx was fractionated using various chromatographic techniques and the isolated compounds were identified based on their chemical and spectroscopic data. The nephroprotective activity was assessed using cadmium chloride-induced nephrotoxicity in the rat model, by measuring some important parameters such as body weight, kidney weight, serum urea, and creatinine levels, oxidative stress markers, inflammatory markers, and histopathological examinations of kidney tissue. Molecular docking studies of the isolated compounds were performed. RESULTS: Three withanolides named 4 ß-hydroxywithanolide E (1), Physalin B (2) and 3α, 14ß-dihydroxywithaphysalin N (3) were isolated and identified from the n-butanol fraction of P. peruviana L calyx extract. The extract and its butanol fraction significantly improved the serum kidney function markers and tissue oxidative status including malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT). Additionally, the extracts significantly decreased the levels of tumor necrosis factor-alpha (TNF-α) and nuclear factor kappaB (NF-κß). Moreover, the histological changes were ameliorated by the extracts. The molecular docking study showed that the isolated compounds displayed a remarkable inhibitory activity against IκB kinase. CONCLUSION: The AME and its butanol fraction of P. peruviana L calyx showed potential nephroprotective activity against cadmium chloride-induced nephrotoxicity which is correlated at least in part to its considerable withanolides content.

All-trans retinoic acid (ATRA) regulates key genes in the RARG-TOP2B pathway and reduces anthracycline-induced cardiotoxicity.

The effectiveness of anthracycline chemotherapeutics (e.g., doxorubicin) is limited by anthracycline-induced cardiotoxicity (ACT). A nonsynonymous variant (S427L) in the retinoic acid receptor-γ (RARG) gene has been associated with ACT. This variant causes reduced RARG activity, which is hypothesized to lead to increased susceptibility to ACT through reduced activation of the retinoic acid pathway. This study explored the effects of activating the retinoic acid pathway using a RAR-agonist, all-trans retinoic acid (ATRA), in human cardiomyocytes and mice treated with doxorubicin. In human cardiomyocytes, ATRA induced the gene expression of RARs (RARG, RARB) and repressed the expression of topoisomerase II enzyme genes (TOP2A, TOP2B), which encode for the molecular targets of anthracyclines and repressed downstream ACT response genes. Importantly, ATRA enhanced cell survival of human cardiomyocytes exposed to doxorubicin. The protective effect of ATRA was also observed in a mouse model (B6C3F1/J) of ACT, in which ATRA treatment improved heart function compared to doxorubicin-only treated mice. Histological analyses of the heart also indicated that ATRA treatment reduced the pathology associated with ACT. These findings provide additional evidence for the retinoic acid pathway's role in ACT and suggest that the RAR activator ATRA can modulate this pathway to reduce ACT.

Chitosan-Functionalized-Graphene Oxide (GO@CS) Beads as an Effective Adsorbent to Remove Cationic Dye from Wastewater.

In this study, the preparation of graphene oxide@chitosan (GO@CS) composite beads was investigated via continuous dropping techniques to remove methylene blue (MB)-dye from an aqueous media. The prepared beads were characterized using various techniques before and after the adsorption of MB. The experimental results showed that the adsorption processes fit the kinetic pseudo-second-order and Langmuir isotherm models. Moreover, the GO@CS beads achieve maximum adsorption capacities of 23.26 mg g-1, which was comparable with other adsorbents in the literature. An important advantage of our adsorbent is that the GO@CS can remove 82.1% of the real sample color within 135 min.

TNFα and IFNγ cooperate for efficient pro- to anti-inflammatory transition of macrophages during muscle regeneration.

IFNγ is traditionally known as a proinflammatory cytokine with diverse roles in antimicrobial and antitumor immunity. Yet, findings regarding its sources and functions during the regeneration process following a sterile injury are conflicting. Here, we show that natural killer (NK) cells are the main source of IFNγ in regenerating muscle. Beyond this cell population, IFNγ production is limited to a small population of T cells. We further show that NK cells do not play a major role in muscle regeneration following an acute injury or in dystrophic mice. Surprisingly, the absence of IFNγ per se also has no effect on muscle regeneration following an acute injury. However, the role of IFNγ is partially unmasked when TNFα is also neutralized, suggesting a compensatory mechanism. Using transgenic mice, we showed that conditional inhibition of IFNGR1 signaling in muscle stem cells or fibro-adipogenic progenitors does not play a major role in muscle regeneration. In contrast to common belief, we found that IFNγ is not present in the early inflammatory phase of the regeneration process but rather peaks when macrophages are acquiring an anti-inflammatory phenotype. Further transcriptomic analysis suggests that IFNγ cooperates with TNFα to regulate the transition of macrophages from pro- to anti-inflammatory states. The absence of the cooperative effect of these cytokines on macrophages, however, does not result in significant regeneration impairment likely due to the presence of other compensatory mechanisms. Our findings support the arising view of IFNγ as a pleiotropic inflammatory regulator rather than an inducer of the inflammatory response.

Fabrication and Characterization of Effective Biochar Biosorbent Derived from Agricultural Waste to Remove Cationic Dyes from Wastewater.

The main aim of this work is to treat sugarcane bagasse agricultural waste and prepare an efficient, promising, and eco-friendly adsorbent material. Biochar is an example of such a material, and it is an extremely versatile and eco-friendly biosorbent to treat wastewater. Crystal violet (CV)-dye and methylene blue (MB)-dye species are examples of serious organic pollutants. Herein, biochar was prepared firstly from sugarcane bagasse (SCB), and then a biochar biosorbent was synthesized through pyrolysis and surface activation with NaOH. SEM, TEM, FTIR, Raman, surface area, XRD, and EDX were used to characterize the investigated materials. The reuse of such waste materials is considered eco-friendly in nature. After that, the adsorption of MB and CV-species from synthetically prepared wastewater using treated biochar was investigated under various conditions. To demonstrate the study's effectiveness, it was attempted to achieve optimum effectiveness at an optimum level by working with time, adsorbent dose, dye concentration, NaCl, pH, and temperature. The number of adsorbed dyes reduced as the dye concentrations increased and marginally decreased with NaCl but increased with the adsorbent dosage, pH, and temperature of the solution increased. Furthermore, it climbed for around 15 min before reaching equilibrium, indicating that all pores were almost full. Under the optimum condition, the removal perecentages of both MB and CV-dyes were ≥98%. The obtained equilibrium data was represented by Langmuir and Freundlich isotherm models. Additionally, the thermodynamic parameters were examined at various temperatures. The results illustrated that the Langmuir isotherm was utilized to explain the experimental adsorption processes with maximum adsorption capacities of MB and CV-dyes were 114.42 and 99.50 mgg-1, respectively. The kinetic data were estimated by pseudo-first and pseudo-second-order equations. The best correlation coefficients of the investigated adsorption processes were described by the pseudo-second-order kinetic model. Finally, the data obtained were compared with some works published during the last four years.