Polymer-mediated nanoformulations: a promising strategy for cancer immunotherapy.

Engineering polymer-based nano-systems have attracted many researchers owing to their unique qualities like shape, size, porosity, mechanical strength, biocompatibility, and biodegradability. Both natural and synthetic polymers can be tuned to get desired surface chemistry and functionalization to improve the efficacy of cancer therapy by promoting targeted delivery to the tumor site. Recent advancements in cancer immunoediting have been able to manage both primary tumor and metastatic lesions via activation of the immune system. The combinations of nano-biotechnology and immunotherapeutic agents have provided positive outcomes by enhancing the host immune response in cancer therapy. The nanoparticles have been functionalized using antibodies, targeted antigens, small molecule ligands, and other novel agents that can interact with biological systems at nanoscale levels. Several polymers, such as polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL), and chitosan, have been approved by the Food and Drug Administration for clinical use in biomedicine. The polymeric nanoformulations such as polymers-antibody/antigen conjugates and polymeric drug conjugates are currently being explored as nanomedicines that can target cancer cells directly or target immune cells to promote anti-cancer immunotherapy. In this review, we focus on scientific developments and advancements on engineered polymeric nano-systems in conjugation with immunotherapeutic agents targeting the tumor microenvironment to improve their efficacy and the safety for better clinical outcomes.

Potential use of cidofovir, brincidofovir, and tecovirimat drugs in fighting monkeypox infection: recent trends and advancements.

Recent years have witnessed the rise of more recent pandemic outbreaks including COVID-19 and monkeypox. A multinational monkeypox outbreak creates a complex situation that necessitates countermeasures to the existing quo. The first incidence of monkeypox was documented in the 1970s, and further outbreaks led to a public health emergency of international concern. Yet as of right now, neither vaccines nor medicines are certain to treat monkeypox. Even the inability of conducting human clinical trials has prevented thousands of patients from receiving effective disease management. The current state of the disease's understanding, the treatment options available, financial resources, and lastly international policies to control an epidemic state are the major obstacles to controlling epidemics. The current review focuses on the epidemiology of monkeypox, scientific ideas, and available treatments, including potential monkeypox therapeutic methods. As a result, a thorough understanding of monkeypox literature will facilitate in the development of new therapeutic medications for the prevention and treatment of monkeypox.

QDs-based fluorescent lateral flow assays for Point-of-care testing of insulin.

Point-of-care testing (POCT) can be performed near the site of the patient to achieve results in a few minutes. Different POCT devices are available in the market, such as microfluidic chips and paper-based lateral flow assays (LFAs). The paper-based LFAs have certain advantages, such as being cheap and disposable, able to detect a wide range of biomolecules, and the fluid flows through them via capillary action eliminating the need for external forces. The LFAs can be optimized for the sensitive and rapid detection of biomolecules. In this study, paper-based fluorescent LFAs platforms using aptamers as the biorecognition molecules were developed for the POCT of insulin. Various parameters were optimized such as concentrations of aptamers, the type of reporter molecules, the volume of sample, and the assay time to quantify insulin levels using a standard LFA reader. The fluorescent LFAs exhibited a linear detection range of 0.1-4 ng.mL-1 with a limit of detection (LOD) 0.1 ng.mL-1. The developed LFAs will help to achieve insulin measurement in a few minutes and will be easy to perform by end-users without the requirement of sophisticated instruments, laboratory set-up, and trained personnel. The developed device will be useful for the measurement of insulin levels in biological samples without the need for pretreatment, reducing the overall cost and time of testing. Moreover, the POCT device were fabricated using paper which is a low-cost (approximately AUD 2 per strip) option and is disposable.Clinical Relevance- POCT monitoring of insulin can facilitate both disease diagnosis and management. The developed LFAs have the capability of rapidly testing insulin concentration within several minutes. It will benefit both patients for at-home daily insulin monitoring and clinicians for hospital rapid insulin testing.

Genistein: a promising modulator of apoptosis and survival signaling in cancer.

Genistein, a commonly occurring isoflavone, has recently gained popularity owing to its ever-expanding spectrum of pharmacological benefits. In addition to health benefits such as improved bone health and reduced postmenopausal complications owing to its phytoestrogen properties, it has been widely evaluated for its anti-cancer potential. Several studies have established the potential for its usage in the management of breast, lung, and prostate cancers, and its usage has significantly evolved from early applications in traditional systems of medicine. This review offers an insight into its current status of usage, the chemistry, and pharmacokinetics of the molecule, an exploration of its apoptotic mechanisms in cancer management, and opportunities for synergism to improve therapeutic outcomes. In addition to this, the authors have presented an overview of recent clinical trials, to offer an understanding of contemporary studies and explore prospects for a greater number of focused trials, moving forward. Advancements in the application of nanotechnology as a strategy to improve safety and efficacy have also been highlighted, with a brief discussion of results from safety and toxicology studies.

Stakeholder Perspectives on the Impact of COVID-19 on the Implementation of a Community-Clinic Linkage Model in New York City.

Community-clinical linkage models (CCLM) have the potential to reduce health disparities, especially in underserved communities; however, the COVID-19 pandemic drastically impacted their implementation. This paper explores the impact of the pandemic on the implementation of CCLM intervention led by community health workers (CHWs) to address diabetes disparities among South Asian patients in New York City. Guided by the Consolidated Framework for Implementation Research (CFIR), 22 stakeholders were interviewed: 7 primary care providers, 7 CHWs, 5 community-based organization (CBO) representatives, and 3 research staff. Semi-structured interviews were conducted; interviews were audio-recorded and transcribed. CFIR constructs guided the identification of barriers and adaptations made across several dimensions of the study's implementation context. We also explored stakeholder-identified adaptations used to mitigate the challenges in the intervention delivery using the Model for Adaptation Design and Impact (MADI) framework. (1) Communication and engagement refers to how stakeholders communicated with participants during the intervention period, including difficulties experienced staying connected with intervention activities during the lockdown. The study team and CHWs developed simple, plain-language guides designed to enhance digital literacy. (2) Intervention/research process describes intervention characteristics and challenges stakeholders faced in implementing components of the intervention during the lockdown. CHWs modified the health curriculum materials delivered remotely to support engagement in the intervention and health promotion. (3) community and implementation context pertains to the social and economic consequences of the lockdown and their effect on intervention implementation. CHWs and CBOs enhanced efforts to provide emotional/mental health support and connected community members to resources to address social needs. Study findings articulate a repository of recommendations for the adaptation of community-delivered programs in under-served communities during a time of public health crises.

Molecular mechanisms behind ROS regulation in cancer: A balancing act between augmented tumorigenesis and cell apoptosis.

ROS include hydroxyl radicals (HO.), superoxide (O2..), and hydrogen peroxide (H2O2). ROS are typically produced under physiological conditions and play crucial roles in living organisms. It is known that ROS, which are created spontaneously by cells through aerobic metabolism in mitochondria, can have either a beneficial or detrimental influence on biological systems. Moderate levels of ROS can cause oxidative damage to proteins, DNA and lipids, which can aid in the pathogenesis of many disorders, including cancer. However, excessive concentrations of ROS can initiate programmed cell death in cancer. Presently, a variety of chemotherapeutic drugs and herbal agents are being investigated to induce ROS-mediated cell death in cancer. Therefore, preserving ROS homeostasis is essential for ensuring normal cell development and survival. On account of a significant association of ROS levels at various concentrations with carcinogenesis in a number of malignancies, further studies are needed to determine the underlying molecular mechanisms and develop the possibilities for intervening in these processes.

Anticancer potential of oroxylin A: from mechanistic insight to synergistic perspectives.

Oroxylin A (OA), a well-known constituent of the root of Scutellariae plants, has been used in ethnomedicine already for centuries in treating various neoplastic disorders. However, only recent molecular studies have revealed the different mechanisms behind its action, demonstrating antiproliferative, anti-inflammatory, and proapoptotic effects, restricting also the spread of cancer cells to distant organs. A variety of cellular targets and modulated signal transduction pathways regulated by OA have been determined in diverse cells derived from different malignant tissues. In this review article, these anticancer activities are thoroughly described, representing OA as a potential lead structure for the design of novel more potent anticancer medicines. In addition, co-effects of this natural compound with conventional anticancer agents are analyzed and the advantages provided by nanotechnological methods for more efficient application of OA are discussed. In this way, OA might represent an excellent example of using ethnopharmacological knowledge for designing modern medicines.

Licorice (Glycyrrhiza glabra L.)-Derived Phytochemicals Target Multiple Signaling Pathways to Confer Oncopreventive and Oncotherapeutic Effects.

Cancer is a highly lethal disease, and its incidence has rapidly increased worldwide over the past few decades. Although chemotherapeutics and surgery are widely used in clinical settings, they are often insufficient to provide the cure for cancer patients. Hence, more effective treatment options are highly needed. Although licorice has been used as a medicinal herb since ancient times, the knowledge about molecular mechanisms behind its diverse bioactivities is still rather new. In this review article, different anticancer properties (antiproliferative, antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory effects) of various bioactive constituents of licorice (Glycyrrhiza glabra L.) are thoroughly described. Multiple licorice constituents have been shown to bind to and inhibit the activities of various cellular targets, including B-cell lymphoma 2, cyclin-dependent kinase 2, phosphatidylinositol 3-kinase, c-Jun N-terminal kinases, mammalian target of rapamycin, nuclear factor-κB, signal transducer and activator of transcription 3, vascular endothelial growth factor, and matrix metalloproteinase-3, resulting in reduced carcinogenesis in several in vitro and in vivo models with no evident toxicity. Emerging evidence is bringing forth licorice as an anticancer agent as well as bottlenecks in its potential clinical application. It is expected that overcoming toxicity-related obstacles by using novel nanotechnological methods might importantly facilitate the use of anticancer properties of licorice-derived phytochemicals in the future. Therefore, anticancer studies with licorice components must be continued. Overall, licorice could be a natural alternative to the present medication for eradicating new emergent illnesses while having just minor side effects.

Gut Microbiota-Assisted Synthesis, Cellular Interactions and Synergistic Perspectives of Equol as a Potent Anticancer Isoflavone.

It is well known that, historically, plants have been an important resource of anticancer agents, providing several clinically approved drugs. Numerous preclinical studies have shown a strong anticancer potential of structurally different phytochemicals, including polyphenolic constituents of plants, flavonoids. In this review article, suppressing effects of equol in different carcinogenesis models are unraveled, highlighting the mechanisms involved in these anticancer activities. Among flavonoids, daidzein is a well-known isoflavone occurring in soybeans and soy products. In a certain part of population, this soy isoflavone is decomposed to equol under the action of gut microflora. Somewhat surprisingly, this degradation product has been shown to be more bioactive than its precursor daidzein, revealing a strong and multifaceted anticancer potential. In this way, it is important to bear in mind that the metabolic conversion of plant flavonoids might lead to products that are even more efficient than the parent compounds themselves, definitely deserving further studies.

Galangin: A metabolite that suppresses anti-neoplastic activities through modulation of oncogenic targets.

With the dramatic increase in cancer incidence all over the world in the last decades, studies on identifying novel efficient anti-cancer agents have been intensified. Historically, natural products have represented one of the most important sources of new lead compounds with a wide range of biological activities. In this article, the multifaceted anti-cancer action of propolis-derived flavonoid, galangin, is presented, discussing its antioxidant, anti-inflammatory, antiproliferative, pro-apoptotic, anti-angiogenic, and anti-metastatic effects in various cancer cells. In addition, co-effects with standard chemotherapeutic drugs as well as other natural compounds are also under discussion, besides highlighting modern nanotechnological advancements for overcoming the low bioavailability issue characteristic of galangin. Although further studies are needed for confirming the anti-cancer potential of galangin in vivo malignant systems, exploring this natural compound might open new perspectives in molecular oncology.

Relationship of Nasolabial Angle with Maxillary Incisor Proclination and Upper Lip Thickness in North Indian Population.

Aim: The aim of the study was to evaluate the relationship between nasolabial angle (NLA) with maxillary incisor proclination (U1-NA) and upper lip thickness (ULT). Materials and methods: Pretreatment lateral cephalometric radiographs of 120 patients were taken, and NLA, U1-NA, and basic ULT measurements were obtained for each patient. Descriptive statistics were calculated for all the variables involved in the study. The correlation was found using the Pearson correlation coefficient (r) test. p < 0.01 was considered statistically significant. Results: The mean values of NLA, upper incisor proclination, and ULT were found to be 91.38° ± 7.10°, 34.21° + 5.17°, and 15.38 ± 1.76 mm, respectively. r (r = -0.583) was found between NLA and upper incisor proclination and (r = -0.040) for NLA and ULT. Conclusion: There is a statistically significant relationship between NLA and U1-NA. How to cite this article: Garg H, Khundrakpam D, Saini V, et al. Relationship of Nasolabial Angle with Maxillary Incisor Proclination and Upper Lip Thickness in North Indian Population. Int J Clin Pediatr Dent 2022;15(5):489-492.

Molecular Evolution of Severe Acute Respiratory Syndrome Coronavirus 2: Hazardous and More Hazardous Strains Behind the Coronavirus Disease 2019 Pandemic and Their Targeting by Drugs and Vaccines.

Within almost the last 2 years, the world has been shaken by the coronavirus disease 2019 (COVID-19) pandemic, which has affected the lives of all people. With nearly 4.92 million deaths by October 19, 2021, and serious health damages in millions of people, COVID-19 has been the most serious global challenge after the Second World War. Besides lost lives and long-term health problems, devastating impact on economics, education, and culture will probably leave a lasting impression on the future. Therefore, the actual extent of losses will become obvious only after years. Moreover, despite the availability of different vaccines and vaccination programs, it is still impossible to forecast what the next steps of the virus are or how near we are to the end of the pandemic. In this article, the route of molecular evolution of the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is thoroughly compiled, highlighting the changes that the virus has undergone during the last 2 years and discussing the approaches that the medical community has undertaken in the fight against virus-induced damages.

Anti-Inflammatory and Anticancer Properties of Birch Bark-Derived Betulin: Recent Developments.

Birch tree bark-derived betulin has attracted scientific interest already for several centuries, being one of the first natural products identified from plants. However, the cellular events regulated by betulin and precise molecular mechanisms under these processes have been begun to be understood only recently. Today, we know that betulin can exert important anticancer activities through modulation of diverse cellular pathways. In this review article, betulin-regulated molecular signaling is unraveled and presented with a special focus on its participation in anti-inflammatory processes, especially by modulating nuclear factor-κB (NF-κB), prostaglandin/COX, and nuclear factor erythroid2-related factor 2 (Nrf2)-mediated cascades. By regulating these diverse pathways, betulin can not only affect the development and progression of different cancers, but also enhance the antitumor action of traditional therapeutic modalities. It is expected that by overcoming the low bioavailability of betulin by encapsulating it into nanocarriers, this promising natural compound may provide novel possibilities for targeting inflammation-related cancers.

Recent Advancements in Nontoxic Halide Perovskites: Beyond Divalent Composition Space.

Since the inception of organic-inorganic hybrid perovskites of ABX3 stoichiometry in 2009, there has been enormous progress in envisaging efficient solar cell materials throughout the world, from both the theoretical and experimental perspectives. Despite achieving 25.5% efficiency, hybrid halide perovskites are still facing two main challenges: toxicity due to the presence of lead and device stability. Two particular families with A3B2X9 and A2MM'X6 stoichiometries have emerged to address these two prime concerns, which have restrained the advancement of solar energy harvesting. Several investigations, both experimental and theoretical, are being conducted to explore the holy-grail materials, which could be optimum for not only efficient but also stable and nontoxic photovoltaics technology. However, the trade-off among stability, efficiency, and toxicity in such solar energy materials is yet to be completely resolved, which requires a systematic overview of A3B2X9- and A2MM'X6-based solar cell materials. Therefore, in this timely and relevant perspective, we have focused on these two particular promising families of perovskite materials. We have portrayed a roadmap projecting the recent advancements from both theoretical and experimental perspectives for these two exciting and promising solar energy material families while amalgamating our critical viewpoint with a future outlook.

Molecular mechanisms underlying chemopreventive potential of butein: Current trends and future perspectives.

Despite extensive efforts, cancer is still often considered as an incurable disease and initiation of novel drug development programs is crucial to improve the prognosis and clinical outcome of patients. One of the major approaches in designing the novel cancer drugs has historically comprised studies of natural agents with diverse anticancer properties. As only a marginal part of natural compounds has been investigated, this approach still represents an attractive source of new potential antitumor molecules. In this review article, different anticancer effects of plant-derived chalcone, butein, are discussed, including its growth inhibitory action, proapoptotic, antiangiogenic and antimetastatic activities in a variety of cancer cells. The molecular mechanisms underlying these effects are presented in detail, revealing interactions of butein with multiple cellular targets (Bcl-2/Bax, caspases, STAT3, cyclins, NF-κB, COX-2, MMP-9, VEGF/R etc.) and regulation of a wide range of intracellular signal transduction pathways. These data altogether allow a good basis for initiating further in vivo studies as well as clinical trials. Along with the efforts to overcome low bioavailability issues generally characteristic to plant metabolites, butein can be considered as a potential lead compound for safe and more efficient cancer drugs in the future.

Formation of Corrugated n = 1 2D Tin Iodide Perovskites and Their Use as Lead-Free Solar Absorbers.

Major strides have been made in the development of materials and devices based around low-dimensional hybrid group 14 metal halide perovskites. Thus far, this work has mostly focused on compounds containing highly toxic Pb, with the analogous less toxic Sn materials being comparatively poorly evolved. In response, the study herein aims to (i) provide insight into the impact of templating cations upon the structure of n = 1 2D tin iodide perovskites (where n refers to the number of contiguous two-dimensional (2D) inorganic layers, i.e., not separated by organic cations) and (ii) examine their potential as light absorbers for photovoltaic (PV) cells. It was discovered through systematic tuning of organic dications that imidazolium rings are able to induce the formation of (110)-oriented materials, including examples of "3 × 3" corrugated Sn-I perovskites. This structural outcome is a consequence of a combination of supramolecular interactions of the two endocyclic N atoms of the imidazolium rings with the Sn-I framework, and the comparatively high tendency of Sn2+ ions to stereochemically express their 5s2 lone pairs . More importantly, the resulting materials feature very short separations between their 2D inorganic layers with iodide-iodide (I···I) contacts as small as 4.174 Å, which is among the shortest ever recorded for 2D tin iodide perovskites. These proximate inorganic distances, combined with the polarizable nature of the imidazolium moiety, eases the separation of photogenerated charge within the materials. This is evident from the measurement of excitonic activation energies as low as 83(10) meV for ImEA[SnI4]. When combined with superior light absorption capabilities relative to their lead congeners, this allowed the fabrication of lead-free solar cells with incident photon-to-current and power conversion efficiencies of up to 70% and 2.26%, respectively, which are among the highest values reported for pure n = 1 2D group 14 metal halide perovskites. In fact, these values are superior to the corresponding lead iodide material, which demonstrates that 2D Sn-based materials have significant potential as less toxic alternatives to their Pb counterparts.

Halide Replacement with Complete Preservation of Crystal Lattice in Mixed-Anion Lanthanide Oxyhalides.

A challenge in anion control in periodic solids is to preserve the crystal lattice while substituting for different anions of widely varying size and hardness. Post-synthetic modification routes that place cations or anions in non-equilibrium configurations are promising; however, such methods remain relatively unexplored for anion placement. Here, we report the synthesis of LaOI nanocrystals by a non-hydrolytic sol-gel condensation reaction and their transformation into LaOBr, LaOCl, and LaOF nanocrystals along hard-soft acid-base principles using post-synthetic metathesis reactions with ammonium halides. Anion displacement proceeds along halide planes, preserving the tetragonal matlockite structure. Energy-variant X-ray excited optical luminesce signatures of alloyed Tb3+ -ions is a sensitive quantum reporter of the preservation of the cation sublattice and hardening of the crystal structure upon anion replacement.

Mechanistic insight into anti-COVID-19 drugs: recent trends and advancements.

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has been established now to be a deadly disease afflicting the whole world with worst consequences on healthcare, economy and day-to-day life activities. Being a communicable disease, which is highly pathogenic in humans, causing cough, throat infection, breathing problems, high fever, muscle pain, and may lead to death in some cases especially those having other comorbid conditions such as heart or kidney problems, and diabetes. Finding an appropriate drug and vaccine candidate against coronavirus disease (COVID-19) remains an ultimate and immediate goal for the global scientific community. Based on previous studies in the literature on SARS-CoV infection, there are a number of drugs that may inhibit the replication of SARS-CoV-2 and its infection. Such drugs comprise of inhibitors of Angiotensin-Converting Enzyme 2 (ACE2), transmembrane Serine Protease 2 (TMPRSS2), nonstructural protein 3C-like protease, nonstructural RNA-dependent RNA polymerase (RdRp) and many more. The antiviral drugs such as chloroquine and hydroxychloroquine, lopinavir and ritonavir as inhibitors for HIV protease, nucleotide analogue remdesivir, and broad-spectrum antiviral drugs are available to treat the SARS-CoV-2-infected patients. Therefore, this review article is planned to gain insight into the mechanism for blocking the entry of SARS-CoV-2, its validation, other inhibition mechanisms, and development of therapeutic drugs and vaccines against SARS-CoV-2.

Efficacy and Safety of New and Emerging Drugs for COVID-19: Favipiravir and Dexamethasone.

PURPOSE OF REVIEW: The widespread respiratory disease of virus known as severe acute respiratory syndrome-coronavirus 2019 (SAR-CoV-2) had infected more than 200 countries and caused pandemic and havoc in the world. RECENT FINDINGS: The genome of the virus was sequenced rapidly to study its mechanism, epidemiology, drugs, and vaccines. Many drugs and vaccines are being studied by researchers to treat and prevent the SARS-CoV-2. Favipiravir and dexamethasone are repurposed drugs which showed therapeutic potential and pharmaceutical efficacy against SARS-CoV-2. SUMMARY: The review describes the path of favipiravir and dexamethasone from chemistry to mechanisms of action to combat SARS-CoV-2. In addition, the potential side effects are also summarized to study their potential to control corona virus 2019.