Silver-doped hydroxyapatite laden chitosan-gelatin nanocomposite scaffolds for bone tissue engineering: an in-vitro and in-ovo evaluation.

Despite the advancements in bone tissue engineering, the majority of implant failures are caused due to microbial contamination. So, efforts are being made to develop biomaterial with antimicrobial property enhancing the regeneration of damaged bone tissue. In the present study, chitosan-gelatin (CG) scaffolds containing silver-doped hydroxyapatite (AgHAP) nanoparticles at 0.5%, 1.0% and 1.5% (w/v) were fabricated by lyophilization technique. The results confirmed the synthesis of AgHAP nanoparticles and showed interconnected porous structure of the nanocomposite scaffolds with 89%-75% porosity. Similarly, the swelling percentage, degradation behavior and compressive modulus of CG-AgHAP nanocomposite scaffolds were 1666%, 40% and 0.7 MPa, respectively. The developed nanocomposite scaffolds revealed better antimicrobial properties and bioactivity. The cell culture studies showed favorable viability of Wharton's jelly stem cells on CG-AgHAP nanocomposite scaffolds. CAM (chorioallantoic membrane) assay determined the angiogenic potential with better visualization of blood vessels in the CAM area. Hence, the obtained results confirmed that CG-AgHAP3 nanocomposite scaffold was the most suitable for bone tissue engineering applications among all scaffolds.

Musashi-2 causes cardiac hypertrophy and heart failure by inducing mitochondrial dysfunction through destabilizing Cluh and Smyd1 mRNA.

Regulation of RNA stability and translation by RNA-binding proteins (RBPs) is a crucial process altering gene expression. Musashi family of RBPs comprising Msi1 and Msi2 is known to control RNA stability and translation. However, despite the presence of MSI2 in the heart, its function remains largely unknown. Here, we aim to explore the cardiac functions of MSI2. We confirmed the presence of MSI2 in the adult mouse, rat heart, and neonatal rat cardiomyocytes. Furthermore, Msi2 was significantly enriched in the heart cardiomyocyte fraction. Next, using RNA-seq data and isoform-specific PCR primers, we identified Msi2 isoforms 1, 4, and 5, and two novel putative isoforms labeled as Msi2 6 and 7 to be expressed in the heart. Overexpression of Msi2 isoforms led to cardiac hypertrophy in cultured cardiomyocytes. Additionally, Msi2 exhibited a significant increase in a pressure-overload model of cardiac hypertrophy. We selected isoforms 4 and 7 to validate the hypertrophic effects due to their unique alternative splicing patterns. AAV9-mediated overexpression of Msi2 isoforms 4 and 7 in murine hearts led to cardiac hypertrophy, dilation, heart failure, and eventually early death, confirming a pathological function for Msi2. Using global proteomics, gene ontology, transmission electron microscopy, seahorse, and transmembrane potential measurement assays, increased MSI2 was found to cause mitochondrial dysfunction in the heart. Mechanistically, we identified Cluh and Smyd1 as direct downstream targets of Msi2. Overexpression of Cluh and Smyd1 inhibited Msi2-induced cardiac malfunction and mitochondrial dysfunction. Collectively, we show that Msi2 induces hypertrophy, mitochondrial dysfunction, and heart failure.

Application of thermosonication for guava juice processing: Impacts on bioactive, microbial, enzymatic and quality attributes.

The present work explores different conditions of thermosonication (TS) processing that would ensure microbiological and enzymatic safety for guava juice while simultaneously maximizing the preservation of its quality attributes. The guava juice was subjected to TS treatment (frequency: 40 kHz; power: 200 W; Temperature: 40, 60, and 80 °C; Time: 2, 6 and 10 min) and was compared with fresh and pasteurized (90 °C/60 s) juice samples. The objectives of the research work were to determine the effect of thermosonication on the quality attributes such as total soluble solids (TSS), pH, titratable acidity, cloud value, color attributes, total phenolic contents, total flavonoid contents, antioxidant activity, ascorbic acid levels, enzymatic, microbiological, and sensory properties. The thermosonicated and pasteurized samples showed no significant (p > 0.05) changes in pH, total soluble solids, and titratable acidity. TS improved the cloud value and color attributes. Furthermore, TS enhanced total phenols (10 to17%), flavonoids (5 to 25%), antioxidant activity (10.45% to 14.55%) and retention of ascorbic acid (61.98-83.32%) relative to control. Thermosonicated sample at 80 °C/10 min gives the maximum inactivation of Pectin methyl esterase (PME), Peroxidase (POD) and Polyphenol oxidase (PPO) enzymes. While both thermosonication and pasteurization drastically decreased the microbial count to undetectable levels, only TS exhibited modest improvement in sensory qualities. The results demonstrated that TS can enhance the overall safety, quality, and commercial viability of guava juice as a practical substitute to pasteurization.

Predictors of Neonatal Mortality: A Retrospective Cross-Sectional Study From the Special Newborn Care Unit of a Tertiary Care Hospital.

Background In India, a significant number of newborns die each year, with Madhya Pradesh having the highest neonatal mortality rate. However, there is a lack of information on factors that can predict neonatal mortality. Objective This study aimed to examine the factors influencing neonatal mortality among neonates admitted to a tertiary care centre's special newborn care unit (SNCU). Methods This retrospective record-based observational study was done at a tertiary care centre, where data from the special newborn care unit (SNCU) from 1st January 2021 to 31st December 2021 was used. We included data of all newborns who were treated in SNCU during the said period and excluded those who got referred or left against medical advice. We abstracted data on age at admission, gender, category, maturity status, birth weight, place of delivery, mode of transport, type of admission, indication of admission, duration of stay and outcome. Qualitative variables were described using frequency and percentage. The chi-square test was used to find out the association of different variables with the outcome, while multivariate logistic regression was conducted to identify risk factors of neonatal mortality. A p-value of <0.05 was considered significant. Results We finalized data of 1052 neonates for analysis. Among them, 846 neonates were successfully discharged while 206 neonates were deceased. The major cause of admission was perinatal asphyxia followed by prematurity. The major cause of mortality in this study was sepsis followed by respiratory distress syndrome, birth asphyxia, and prematurity. Mortality of neonates was significantly associated with maturity status, birth weight, place of delivery, age during admission and duration of stay. Prematurity (OR=3.762, 95% CI:1.93-7.33), birth weight 1000-1499g (OR=4.78, 95% CI:2.21-10.32), birth weight <1000g (OR=25.11, 95% CI:5.71-110.24), age at admission <1-day (OR=2.312, 95% CI:1.03-5.19), duration of stay 1-3-days (OR=12.98, 95% CI:7.48-22.52) and <1-day (OR=1271.88, 95% CI:121.39-13325.69) were significant predictors of mortality in our study. Conclusion Our study emphasizes monitoring and addressing risk factors like maturity status, birth weight, and age at admission to reduce neonatal mortality, with a focus on early management of preterm births and low birth weight.

African Control of Hypertension through Innovative Epidemiology and a Vibrant Ecosystem (ACHIEVE): novel strategies for accelerating hypertension control in Africa.

Hypertension is a leading preventable and controllable risk factor for cardiovascular and cerebrovascular diseases and the leading preventable risk for death globally. With a prevalence of nearly 50% and 93% of cases uncontrolled, very little progress has been made in detecting, treating, and controlling hypertension in Africa over the past thirty years. We propose the African Control of Hypertension through Innovative Epidemiology and a Vibrant Ecosystem (ACHIEVE) to implement the HEARTS package for improved surveillance, prevention, treatment/acute care of hypertension, and rehabilitation of those with hypertension complications across the life course. The ecosystem will apply the principles of an iterative implementation cycle by developing and deploying pragmatic solutions through the contextualization of interventions tailored to navigate barriers and enhance facilitators to deliver maximum impact through effective communication and active participation of all stakeholders in the implementation environment. Ten key strategic actions are proposed for implementation to reduce the burden of hypertension in Africa.

Cerium oxide nanoparticles disseminated chitosan gelatin scaffold for bone tissue engineering applications.

Cell-free and cell-loaded constructs are used to bridge the critical-sized bone defect. Oxidative stress at the site of the bone defects is a major interference that slows bone healing. Recently, there has been an increase in interest in enhancing the properties of three-dimensional scaffolds with free radical scavenging materials. Cerium oxide nanoparticles (CNPs) can scavenge free radicals due to their redox-modulating property. In this study, freeze-drying was used to fabricate CG-CNPs nanocomposite scaffolds using gelatin (G), chitosan (C), and cerium oxide nanoparticles. Physico-chemical, mechanical, and biological characterization of CG-CNPs scaffolds were studied. CG-CNPs scaffolds demonstrated better results in terms of physicochemical, mechanical, and biological properties as compared to CG-scaffold. CG-CNPs scaffolds were cyto-friendly to MC3T3-E1 cells studied by performing in-vitro and in-ovo studies. The scaffold's antimicrobial study revealed high inhibition zones against Gram-positive and Gram-negative bacteria. With 79 % porosity, 45.99 % weight loss, 178.25 kPa compressive modulus, and 1.83 Ca/P ratio, the CG-CNP2 scaffold displays the best characteristics. As a result, the CG-CNP2 scaffolds are highly biocompatible and could be applied to repair bone defects.

Surgical cotton microfibers loaded with proteins and apatite: A potential platform for bone tissue engineering.

Tissue engineering has emerged as the best alternative to replacing damaged tissue/organs. However, the cost of scaffold materials continues to be a significant obstacle; thus, developing inexpensive scaffolds is strongly encouraged. In this study, cellulose microfibers (C), gelatin (G), egg white (EW), and nanohydroxyapatite (nHA) were assembled into a quaternary scaffold using EDC-NHS crosslinking, followed by freeze-drying method. Cellulose microfibers as a scaffold have only received a limited amount of research due to the absence of an intrinsic three-dimensional structure. Gelatin, more likely to interact chemically with collagen, was used to provide a stable structure to the cellulose microfibers. EW was supposed to provide the scaffold with numerous cell attachment sites. nHA was chosen to enhance the scaffold's bone-bonding properties. Physico-chemical, mechanical, and biological characterization of scaffolds were studied. In-vitro using MG-63 cells and in-ovo studies revealed that all scaffolds were biocompatible. The results of the DPPH assay demonstrate the ability of CGEWnHA to reduce free radicals. The CGEWnHA scaffold exhibits the best properties with 56.84 ± 28.45 µm average pore size, 75 ± 1.4 % porosity, 39.23 % weight loss, 109.19 ± 0.98 kPa compressive modulus, and 1.72 Ca/P ratio. As a result, the constructed CGEWnHA scaffold appears to be a viable choice for BTE applications.

Scaffold Fabrication Techniques of Biomaterials for Bone Tissue Engineering: A Critical Review.

Bone tissue engineering (BTE) is a promising alternative to repair bone defects using biomaterial scaffolds, cells, and growth factors to attain satisfactory outcomes. This review targets the fabrication of bone scaffolds, such as the conventional and electrohydrodynamic techniques, for the treatment of bone defects as an alternative to autograft, allograft, and xenograft sources. Additionally, the modern approaches to fabricating bone constructs by additive manufacturing, injection molding, microsphere-based sintering, and 4D printing techniques, providing a favorable environment for bone regeneration, function, and viability, are thoroughly discussed. The polymers used, fabrication methods, advantages, and limitations in bone tissue engineering application are also emphasized. This review also provides a future outlook regarding the potential of BTE as well as its possibilities in clinical trials.

Phytochemicals targeting NF-κB signaling: Potential anti-cancer interventions.

Nuclear factor κB (NF-κB) is a ubiquitous regulator of the signalome and is indispensable for various biological cell functions. NF-κB consists of five transcription factors that execute both cytoplasmic and nuclear signaling processes in cells. NF-κB is the only signaling molecule that governs both pro- and anti-apoptotic, and pro- and anti-inflammatory responses. This is due to the canonical and non-canonical components of the NF-κB signaling pathway. Together, these pathways orchestrate cancer-related inflammation, hyperplasia, neoplasia, and metastasis. Non-canonical NF-κB pathways are particularly involved in the chemoresistance of cancer cells. In view of its pivotal role in cancer progression, NF-κB represents a potentially significant therapeutic target for modifying tumor cell behavior. Several phytochemicals are known to modulate NF-κB pathways through the stabilization of its inhibitor, IκB, by inhibiting phosphorylation and ubiquitination thereof. Several natural pharmacophores are known to inhibit the nuclear translocation of NF-κB and associated pro-inflammatory responses and cell survival pathways. In view of this and the high degree of specificity exhibited by various phytochemicals for the NF-κB component, we herein present an in-depth overview of these phytochemicals and discuss their mode of interaction with the NF-κB signaling pathways for controlling the fate of tumor cells for cancer-directed interventions.

SARS-CoV-2 cases reported from long-term residential facilities (care homes) in South Africa: a retrospective cohort study.

BACKGROUND: Globally, long-term care facilities (LTCFs) experienced a large burden of deaths during the COVID-19 pandemic. The study aimed to describe the temporal trends as well as the characteristics and risk factors for mortality among residents and staff who tested positive for SARS-CoV-2 in selected LTCFs across South Africa. METHOD: We analysed data reported to the DATCOV sentinel surveillance system by 45 LTCFs. Outbreaks in LTCFs were defined as large if more than one-third of residents and staff had been infected or there were more than 20 epidemiologically linked cases. Multivariable logistic regression was used to assess risk factors for mortality amongst LTCF residents. RESULTS: A total of 2324 SARS-CoV-2 cases were reported from 5 March 2020 through 31 July 2021; 1504 (65%) were residents and 820 (35%) staff. Among LTCFs, 6 reported sporadic cases and 39 experienced outbreaks. Of those reporting outbreaks, 10 (26%) reported one and 29 (74%) reported more than one outbreak. There were 48 (66.7%) small outbreaks and 24 (33.3%) large outbreaks reported. There were 30 outbreaks reported in the first wave, 21 in the second wave and 15 in the third wave, with 6 outbreaks reporting between waves. There were 1259 cases during the first COVID-19 wave, 362 during the second wave, and 299 during the current third wave. The case fatality ratio was 9% (138/1504) among residents and 0.5% (4/820) among staff. On multivariable analysis, factors associated with SARS-CoV-2 mortality among LTCF residents were age 40-59 years, 60-79 years and ≥ 80 years compared to < 40 years and being a resident in a LTCF in Free State or Northern Cape compared to Western Cape. Compared to pre-wave 1, there was a decreased risk of mortality in wave 1, post-wave 1, wave 2, post-wave 2 and wave 3. CONCLUSION: The analysis of SARS-CoV-2 cases in sentinel LTCFs in South Africa points to an encouraging trend of decreasing numbers of outbreaks, cases and risk for mortality since the first wave. LTCFs are likely to have learnt from international experience and adopted national protocols, which include improved measures to limit transmission and administer early and appropriate clinical care.

How to Improve Awareness, Treatment, and Control of Hypertension in Africa, and How to Reduce Its Consequences: A Call to Action From the World Hypertension League.

Hypertension is the leading preventable risk factor for cardiovascular diseases and disability globally. In low- and middle-income countries hypertension has a major social impact, increasing the disease burden and costs for national health systems. The present call to action aims to stimulate all African countries to adopt several solutions to achieve better hypertension management. The following 3 goals should be achieved in Africa by 2030: (1) 80% of adults with high blood pressure in Africa are diagnosed; (2) 80% of diagnosed hypertensives, that is, 64% of all hypertensives, are treated; and (3) 80% of treated hypertensive patients are controlled. To achieve these aims, we call on individuals and organizations from government, private sector, health care, and civil society in Africa and indeed on all Africans to undertake a few specific high priority actions. The aim is to improve the detection, diagnosis, management, and control of hypertension, now considered to be the leading preventable killer in Africa.

Cutting the umbilical cord: Cancer stem cell-targeted therapeutics.

Cancer Stem Cells (CSCs) are a notoriously quiescent subpopulation of cells within heterogeneous tumors exhibiting self-renewal, differentiation and drug-resistant capabilities leading to tumor relapse. Heterogeneous cell populations in tumor microenvironment develop an elaborate network of signalling and factors supporting the CSC population within a niche. Identification of specific biomarkers for CSCs facilitates their isolation. CSCs demonstrate abilities that bypass immune surveillance, exhibit resistance to therapy, and induce cancer recurrence while promoting altered metabolism of the bulk tumor, thereby encouraging metastasis. The fight against cancer is prone to relapse without discussing the issue of CSCs, making it imperative for encapsulation of current studies. In this review, we provide extensive knowledge of recent therapeutics developed that target CSCs via multiple signalling cascades, altered metabolism and the tumor microenvironment. Thorough understanding of the functioning of CSCs, their interaction with different cells in the tumor microenvironment as well as current gaps in knowledge are addressed. We present possible strategies to disrupt the cellular and molecular interplay within the tumor microenvironment and make it less conducive for CSCs, which may aid in their eradication with subsequently better treatment outcomes. In conclusion, we discuss a brief yet functional idea of emerging concepts in CSC biology to develop efficient therapeutics acting on cancer recurrence and metastasis.

Yin and yang of immunological memory in controlling infections: Overriding self defence mechanisms.

Immunological memory is critical for host immunity and decisive for individual to respond exponentially to previously encountered infection. Both T and B cell memory are known to orchestrate immunological memory with their central and effector memory arms contributing in prolonged immunity/defence mechanisms of host. While central memory helps in maintaining prolonged immunity for a particular infection, effector memory helps in keeping local/seasonal infection in control. In addition to this, generation of long-lived plasma cells is pivotal for generating neutralizing antibodies which can enhance recall and B cell memory to control re-infection. In view of this, scaling up memory response is one of the major objectives for the expected outcome of vaccination. In this line, this review deals with the significance of memory cells, molecular pathways of their development, maintenance, epigenetic regulation and negative regulation in various infections. We have also highlighted the significance of both T and B cell memory responses in the vaccination approaches against range of infections which is not fully explored so far.[Box: see text].

Phytochemicals targeting NF-κB signaling:Potential anti-cancer interventions / 药物分析学报

Nuclear factor κB(NF-κB)is a ubiquitous regulator of the signalome and is indispensable for various biological cell functions.NF-κB consists of five transcription factors that execute both cytoplasmic and nuclear signaling processes in cells.NF-κB is the only signaling molecule that governs both pro-and anti-apoptotic,and pro-and anti-inflammatory responses.This is due to the canonical and non-canonical components of the NF-κB signaling pathway.Together,these pathways orchestrate cancer-related inflammation,hyperplasia,neoplasia,and metastasis.Non-canonical NF-κB pathways are particularly involved in the chemoresistance of cancer cells.In view of its pivotal role in cancer progression,NF-κB represents a potentially significant therapeutic target for modifying tumor cell behavior.Several phy-tochemicals are known to modulate NF-κB pathways through the stabilization of its inhibitor,IKB,by inhibiting phosphorylation and ubiquitination thereof.Several natural pharmacophores are known to inhibit the nuclear translocation of NF-κB and associated pro-inflammatory responses and cell survival pathways.In view of this and the high degree of specificity exhibited by various phytochemicals for the NF-κB component,we herein present an in-depth overview of these phytochemicals and discuss their mode of interaction with the NF-κB signaling pathways for controlling the fate of tumor cells for cancer-directed interventions.

Correlations between ligand field Δ o, spin crossover T 1/2 and redox potential E pa in a family of five dinuclear helicates.

A family of five new bis-bidentate azole-triazole Rat ligands (1,3-bis(5-(azole)-4-isobutyl-4H-1,2,4-triazol-3-yl)benzene), varying in choice of azole (2-imidazole, 4-imidazole, 1-methyl-4-imidazole, 4-oxazole and 4-thiazole), and the corresponding family of spin-crossover (SCO) and redox active triply bridged dinuclear helicates, [FeII 2L3]4+, has been prepared and characterised. X-ray crystal structures show all five Fe(ii) helicates are low spin at 100 K. Importantly, DOSY NMR confirms the intactness of these SCO-active dinuclear helicates in D3-MeCN solution, regardless of HS fraction: γ HS(298 K) = 0-0.81. Variable temperature 1H NMR Evans and UV-vis studies reveal that the helicates are SCO-active in MeCN solution. Indeed, the choice of azole in the Rat ligand used in [Fe2L3]4+ tunes: (a) solution SCO T 1/2 from 247 to 471 K, and (b) reversible redox potential, E m(FeII/III), from 0.25 to 0.67 V for four helicates, whilst one has an irreversible redox process, E pa = 0.78 V, vs. 0.01 M AgNO3/Ag. For the four reversible redox systems, a strong correlation (R 2 = 0.99) is observed between T 1/2 and E pa. Finally, the analogous Ni(ii) helicates have been prepared to obtain Δ o, establishing: (a) the ligand field strength order of the ligands: 4-imidazole (11 420) ∼ 1-methyl-4-imidazole (11 430) < 2-imidazole (11 505) ∼ 4-oxazole (11 516) < 4-thiazole (11 804 cm-1), (b) that Δ o ([NiII 2L3]4+) strongly correlates (R 2 = 0.87) with T 1/2 ([FeII 2L3]4+), and (c) interestingly that Δ o strongly correlates (R 2 = 0.98) with E pa for the four helicates with reversible redox, so the stronger the ligand field strength, the harder it is to oxidise the Fe(ii) to Fe(iii).

Investigating alterations in the cellular envelope of Staphylococcus aureus in simulated microgravity using a random positioning machine.

Continuous rotation of liquid bacterial culture in random positioning machine (RPM) causes formation of a colloidal bacterial culture in the culture tube, due to lack of sedimentation and convection. Interestingly, similar colloidal bacterial cultures can also be seen in suspended bacterial cultures in a spaceflight environment. Thus, as a consequence of no sedimentation, an alteration in the microenvironment of each bacterial cell in simulated microgravity is introduced, compared to the bacterial culture grown in normal gravity wherein they sediment slowly at the bottom of the culture tube. Apparently, a bacterial cell can sense changes in its environment through various receptors and sensors present at its surface, thus it can be speculated that this change in its microenvironment might induce changes in its cell wall and cell surface properties. In our study, changes in growth kinetics, cell wall constitution using FTIR (Fourier Transform Infrared Spectroscopy), cell surface hydrophobicity, autoaggregation ability and antibiotic susceptibility of Staphylococcus aureus NCIM 2079 strain, in simulated microgravity (using RPM) was studied in detail. Noteworthy alterations in its growth kinetics, cell wall constitution, cell surface hydrophobicity, autoaggregation ability and antibiotic susceptibility especially to Erythromycin and Clindamycin were observed. Our data suggests that microgravity may cause alterations in the cellular envelope of planktonic S.aureus cultures.

Cotton pulp for bone tissue engineering.

Cellulose, a polysaccharide of ß (1-4) linked D-glucose units, is a cheap, eco-friendly and most abundant natural polymer on this planet. Among various cellulosic materials, cotton cellulose is readily available, lignin-free, FDA approved, and widely used in the medical field because of its higher degree of biocompatibility and non-cytotoxic nature. Though cotton cellulose showed essential material properties for scaffold design, the least priority had been given to this material. The present study aimed at exploring the fabrication of scaffold using cotton microfibers for bone tissue engineering application. The study also aimed at improving the mechanical, physio-chemical and osteogenic properties of the microfibrous scaffold by crosslinking with citric acid and further modified with gelatin. FTIR indicated some interactions between cellulose, citric acid and gelatin within the scaffolds, while XRD results demonstrated the crystalline nature of scaffolds. Porosity and swelling studies demonstrated that all scaffolds are hydrophilic and porous. The microporous interconnected network of scaffolds was confirmed by FESEM. FESEM micrographs and MTT assay confirmed that all scaffolds were nontoxic to MG 63. Based on findings, it was concluded that gelatin coated cotton cellulose microfibers crosslinked with citric acid scaffold would be a potential template for bone tissue engineering.

Non-coding RNAs: Regulators of valvular calcification.

There is currently a growing global burden of valvular heart diseases due to aging populations and changing lifestyles. Valvular heart diseases mainly include the malfunctioning of aortic and mitral valves and are characterized by extensive tissue remodeling, which includes calcification, endothelial dysfunction, and endothelial-mesenchymal transition. These valvular remodeling processes are known to be regulated by protein-coding genes as well as non-coding genes. Here, we have summarized studies highlighting the non-coding RNA mediated regulation of valvular tissue remodeling and their potential therapeutic benefits. Additionally, studies investigating the diagnostic capability of circulating non-coding RNA molecules in valvular diseases are also summarized. Overall, of the various candidates, several studies have highlighted miR-214 and miR-204 as central regulators of valvular calcification.