Recent Trends in Bio-nanomaterials and Non-invasive Combinatorial Approaches of Photothermal Therapy against Cancer.

In 2020, approximately 10 million deaths worldwide were attributed to cancer, making it the primary cause of death globally. Photothermal therapy (PTT) is one of the novel ways to treat and abolish cancer. PTT significantly impacts cancer theranostics compared to other therapies like surgery, chemotherapy, and radiotherapy due to its remarkable binding capability to tumor sites and lower invasiveness into normal healthy tissues. PTT relies on photothermal agents (PTAs), which generate heat by absorbing the near-infrared (NIR) light and destroying cancer cells. Several PTT agents remain longer in the reticuloendothelial system (RES) and induce toxicity, restricting their use in the biomedical field. To overcome this problem, the usage of biodegradable nano-photothermal agents is required. This review has discussed the PTT mechanism of action and different types of novel bio-nanomaterials used for PTT. We also focussed on the combinatorial effects of PTT with other cancer therapies and their effect on human health. The role of LED lights and mild hypothermia in PTT has been discussed briefly in this review.

Effectiveness of structured teaching program on parents' knowledge about child physical abuse.

BACKGROUND: The issue of child physical abuse (CPA) is complex and challenging to study. According to World Health Organization fact sheets for 2020, about 3 in 4 children between 2 and 4 years of age regularly face physical maltreatment by parents or caregivers. It may cause a lifelong impact on physical and mental health. OBJECTIVE: To assess the parents' knowledge and to evaluate the effectiveness of the structured teaching program (STP) regarding child physical abuse (CPA) among parents. METHODS AND MATERIALS: The pre-experimental, "One-group Pre-test Post-test design" was adopted for this study. Parents of children who were admitted for treatment in the child psychiatry centre (CPC) of a tertiary care referral center between January 2019 and January 2020 were recruited for this study. Thirty parents were recruited with a convenience sampling technique. The study was conducted through an online platform (Zoom). Pre-test and post-tests were conducted through Google survey form. Data were collected with a self-developed knowledge questionnaire on CAP. An online structured teaching program (STP) was administered for three alternative days after the pre-test assessment. The post-test assessment was conducted at a two-point time, that is immediately after the STP and after the one-week gap. Descriptive and inferential statistics were used to analyze the data. "One-group Pre-test Post-test design" was adopted for this study. Parents of children who were admitted for treatment in the child psychiatry centre (CPC) of a tertiary care referral center between January 2019 and January 2020 were recruited for this study. Thirty parents were recruited with a convenience sampling technique. The study was conducted through an online platform (Zoom). Pre-test and post-tests were conducted through Google survey form. Data were collected with a self-developed knowledge questionnaire on CAP. An online structured teaching program (STP) was administered for three alternative days after the pre-test assessment. The post-test assessment was conducted at a two-point time, that is immediately after the STP and after the one-week gap. Descriptive and inferential statistics were used to analyze the data. RESULTS: The pre-test knowledge assessment means score regarding child physical abuse was found to be 12, with a standard deviation of 1.73. In the post-test one, 17.30 ± 1.39 and in the post-test two, 16 ± 1.55 with P < 0.001. Analysis revealed statistically significant improvement was found in the post-test knowledge regarding child physical abuse among the parents. There was no significant (p < 0.05) relationship found between the socio-demographic variables of the participants and their pre-intervention knowledge scores on child physical abuse. CONCLUSIONS: The study findings reveal that parents have a fair knowledge of CPA and the STP was effective and feasible to administer in improving the subjects' knowledge regarding child physical abuse.

Fungal Endophytes to Combat Biotic and Abiotic Stresses for Climate-Smart and Sustainable Agriculture.

The agricultural sustainability concept considers higher food production combating biotic and abiotic stresses, socio-economic well-being, and environmental conservation. On the contrary, global warming-led climatic changes have appalling consequences on agriculture, generating shifting rainfall patterns, high temperature, CO2, drought, etc., prompting abiotic stress conditions for plants. Such stresses abandon the plants to thrive, demoting food productivity and ultimately hampering food security. Though environmental issues are natural and cannot be regulated, plants can still be enabled to endure these abnormal abiotic conditions, reinforcing the stress resilience in an eco-friendly fashion by incorporating fungal endophytes. Endophytic fungi are a group of subtle, non-pathogenic microorganisms establishing a mutualistic association with diverse plant species. Their varied association with the host plant under dynamic environments boosts the endogenic tolerance mechanism of the host plant against various stresses via overall modulations of local and systemic mechanisms accompanied by higher antioxidants secretion, ample enough to scavenge Reactive Oxygen Species (ROS) hence, coping over-expression of defensive redox regulatory system of host plant as an aversion to stressed condition. They are also reported to ameliorate plants toward biotic stress mitigation and elevate phytohormone levels forging them worthy enough to be used as biocontrol agents and as biofertilizers against various pathogens, promoting crop improvement and soil improvement, respectively. This review summarizes the present-day conception of the endophytic fungi, their diversity in various crops, and the molecular mechanism behind abiotic and biotic resistance prompting climate-resilient aided sustainable agriculture.

Collectins, H-ficolin and LL-37 reduce influence viral replication in human monocytes and modulate virus-induced cytokine production.

Infiltrating activated monocytes are important mediators of damaging inflammation during influenza A virus (IAV) infection. We show that soluble respiratory proteins [collectins, surfactant proteins D (SP-D) and mannose binding lectin (MBL), H-ficolin and LL-37] inhibit replication of seasonal IAV in human monocytes. The collectins and H-ficolin also increased viral uptake by the cells, while LL-37 did not. H-ficolin was able to inhibit replication of the 2009 pandemic H1N1 strain (Cal09) in monocytes, but SP-D and LL-37 had significantly fewer inhibitory effects on this strain than on seasonal IAV. All of these proteins reduced IAV-induced TNF-α production, even in instances when viral replication was not reduced. We used modified recombinant versions of SP-D, MBL and ficolin to elucidate mechanisms through which these proteins alter monocyte interactions with IAV. We demonstrate the importance of the multimeric structure, and of binding properties of the lectin domain, in mediating antiviral and opsonic activity of the proteins. Hence, soluble inhibitors present in airway lining fluid may aid clearance of IAV by promoting monocyte uptake of the virus, while reducing viral replication and virus-induced TNF-α responses in these cells. However, SP-D and LL-37 have reduced ability to inhibit replication of pandemic IAV in monocytes.

LL-37 modulates human neutrophil responses to influenza A virus.

Recent studies have shown that the human cathelicidin, LL-37, has antiviral activity against IAV in vitro and in vivo. Neutrophils are important cellular components of the initial innate response to IAV infection. In addition to its direct antimicrobial activities, LL-37 has important immunomodulatory effects. In this study, we explore how LL-37 affects interactions of IAV with human neutrophils. LL-37 did not alter neutrophil uptake of IAV but significantly increased neutrophil H2O2 responses to the virus. IAV stimulated production of NETs in vitro, and this response was increased by preincubating the virus with LL-37. NADPH-oxidase blockade did not reduce IAV-induced NET formation or the increased NET response stimulated by LL-37 + IAV. The increased respiratory burst and NET responses were, however, inhibited by preincubating cells with a formyl peptide receptor blocker, indicating that LL-37 engages these receptors when complexed with IAV. Responses to IAV alone were not inhibited by formyl peptide receptor blockade. It has been reported that LL-37 reduces proinflammatory cytokine responses during IAV infection in vivo. We now show that IAV alone potentiated release of IL-8 from neutrophils, and preincubation with LL-37 reduced IAV-stimulated IL-8 release. These results confirm that LL-37 modulates human neutrophil responses to IAV in a distinctive manner and could have important bearing on the protective effects of LL-37 during IAV infection in vivo.

The human cathelicidin LL-37 inhibits influenza A viruses through a mechanism distinct from that of surfactant protein D or defensins.

LL-37, the only human cathelicidin, is a cationic antimicrobial peptide with antibacterial and antifungal activity. LL-37 is released from neutrophil granules and produced by epithelial cells. It has been implicated in host defence against influenza A virus (IAV) in recent studies. We now demonstrate dose-related neutralizing activity of LL-37 against several seasonal and mouse-adapted IAV strains. The ability of LL-37 to inhibit these IAV strains resulted mainly from direct effects on the virus, since pre-incubation of virus with LL-37 was needed for optimal inhibition. LL-37 bound high-density lipoprotein (HDL), and pre-incubation of LL-37 with human serum or HDL reduced its antiviral activity. LL-37 did not inhibit viral association with epithelial cells as assessed by quantitative RT-PCR or confocal microscopy. This finding contrasted with results obtained with surfactant protein D (SP-D). Unlike collectins or human neutrophil defensins (HNPs), LL-37 did not induce viral aggregation under electron microscopy. In the electron microscopy studies, LL-37 appeared to cause disruption of viral membranes. LL-37 had additive antiviral activity when combined with other innate inhibitors like SP-D, surfactant protein A and HNPs. Unlike HNPs, LL-37 did not bind SP-D significantly. These findings indicate that LL-37 contributes to host defence against IAV through a mechanism distinct from that of SP-D and HNPs.

Human H-ficolin inhibits replication of seasonal and pandemic influenza A viruses.

The collectins have been shown to have a role in host defense against influenza A virus (IAV) and other significant viral pathogens (e.g., HIV). The ficolins are a related group of innate immune proteins that are present at relatively high concentrations in serum, but also in respiratory secretions; however, there has been little study of the role of ficolins in viral infection. In this study, we demonstrate that purified recombinant human H-ficolin and H-ficolin in human serum and bronchoalveolar lavage fluid bind to IAV and inhibit viral infectivity and hemagglutination activity in vitro. Removal of ficolins from human serum or bronchoalveolar lavage fluid reduces their antiviral activity. Inhibition of IAV did not involve the calcium-dependent lectin activity of H-ficolin. We demonstrate that H-ficolin is sialylated and that removal of sialic acid abrogates IAV inhibition, while addition of the neuraminidase inhibitor oseltamivir potentiates neutralization, hemagglutinin inhibition, and viral aggregation caused by H-ficolin. Pandemic and mouse-adapted strains of IAV are generally not inhibited by the collectins surfactant protein D or mannose binding lectin because of a paucity of glycan attachments on the hemagglutinin of these strains. In contrast, H-ficolin inhibited both the mouse-adapted PR-8 H1N1 strain and a pandemic H1N1 strain from 2009. H-ficolin also fixed complement to a surface coated with IAV. These findings suggest that H-ficolin contributes to host defense against IAV.

Hapivirins and diprovirins: novel θ-defensin analogs with potent activity against influenza A virus.

θ-Defensins are cyclic octadecapeptides found in nonhuman primates whose broad antiviral spectrum includes HIV-1, HSV-1, severe acute respiratory syndrome coronavirus, and influenza A virus (IAV). We previously reported that synthetic θ-defensins called retrocyclins can neutralize and aggregate various strains of IAV and increase IAV uptake by neutrophils. This study describes two families of peptides, hapivirins and diprovirins, whose design was inspired by retrocyclins. The goal was to develop smaller partially cyclic peptides that retain the antiviral activity of retrocyclins, while being easier to synthesize. The novel peptides also allowed for systemic substitution of key residues to evaluate the role of charge or hydrophobicity on antiviral activity. Seventy-two hapivirin or diprovirin peptides are described in this work, including several whose anti-IAV activity equals or exceeds that of normal α- or θ-defensins. Some of these also had strong antibacterial and antifungal activity. These new peptides were active against H3N2 and H1N1 strains of IAV. Structural features imparting strong antiviral activity were identified through iterative cycles of synthesis and testing. Our findings show the importance of hydrophobic residues for antiviral activity and show that pegylation, which often increases a peptide's serum t(1/2) in vivo, can increase the antiviral activity of DpVs. The new peptides acted at an early phase of viral infection, and, when combined with pulmonary surfactant protein D, their antiviral effects were additive. The peptides strongly increased neutrophil and macrophage uptake of IAV, while inhibiting monocyte cytokine generation. Development of modified θ-defensin analogs provides an approach for creating novel antiviral agents for IAV infections.

Glycine-assisted enhancement of 1,4-beta-d-xylan xylanohydrolase activity at alkaline pH with a pH optimum shift.

This is the first report describing the enhancement of xylanase activity by the neutral amino acid glycine. Xylanase activity is increased seven-fold at alkaline pH in the presence of glycine and its pH optimum is shifted from pH 7 to 8 without using any protein engineering techniques. Analysis of the steady-state kinetics revealed that glycine in the reaction mixture increases the K(m) and k(cat) values of the enzyme. Chemoaffinity labeling and studies using glycine esters indicate an involvement of the carboxylate ion of glycine in enhancing xylanase catalytic activity. A novel possible mechanism for the glycine-assisted catalytic action of xylanase is proposed.