Glycyrrhizin functionalized CuS Nanoprobes for NIR Light-based therapeutic mitigation of acne vulgaris.

Acne Vulgaris or Acne is a multifactorial bacterial infection caused by Propionibacterium acne, leading to inflammation and decreased quality of life, especially in adolescence. Currently, antibiotics and retinoids are preferred for treating acne. However, their continuous usage may lead to anti-microbial resistance and other side effects. Therefore, research on developing effective strategies to reduce antimicrobial resistance and improve acne healing is ongoing. The current work reports the synthesis and evaluation of near-infrared light-absorbing copper sulfide (CuS) nanoparticles loaded with a biomolecule, Glycyrrhizin (Ga). The photothermal efficacy studies, and in-vitro and in-vivo experiments indicated that the Ga-CuS NPs generated localized hyperthermia in acne-causing bacteria, leading to their complete growth inhibition. The results indicated that the Ga-Cus NPs possess excellent antibacterial and anti-inflammatory properties in the acne and inflammatory models. This could be from the synergistic effect of CuS NPs mediated mild Photothermal effect and inherent pharmacological properties of Ga. Further detailed studies of the formulations can pave the way for application in cosmetic clinics for the effective and minimally invasive management of Acne-like conditions.

Inflammatory-stimuli-responsive turn-on NIR fluorogenic theranostic prodrug: adjuvant delivery of diclofenac and hydrogen sulfide attenuates acute inflammatory disorders.

Prolonged use of very commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with undesired side effects, including gastrointestinal ulcers due to the non-selective inhibition of cyclooxygenases. We describe the development of an inflammatory-stimuli-responsive turn-on fluorogenic theranostic prodrug DCF-HS for adjuvant drug delivery. Upon activation by reactive oxygen species (ROS), the prodrug releases diclofenac DCF (active drug) and the NIR fluorophore DCI-NH2 along with carbonyl sulfide (COS). The second activation of COS by the enzyme carbonic anhydrase (CA) generates hydrogen sulfide (H2S). The prodrug was conveniently synthesized using multi-step organic synthesis. The UV-Vis and fluorescence studies revealed the selective reactivity of DCF-HS towards ROS such as H2O2 in the aqueous phase and the desired uncaging of the drug DCF with turn-on NIR fluorescent reporter under physiological conditions. Furthermore, the release of fluorophore DCI-NH2 and drug DCF was confirmed using the reverse phase HPLC method. Compatibility of prodrug activation was studied next in the cellular medium. The prodrug DCF-HS was non-toxic in a representative cancer cell line (HeLa) and a macrophage cell line (RAW 264.7) up to 100 µM concentration, indicating its biocompatibility. The intracellular ROS-mediated activation of the prodrug with the release of NIR dye DCI-NH2 and H2S was investigated in HeLa cells using the H2S-selective probe WSP2. The anti-inflammatory activity of the active drug DCF from the prodrug DCF-HS was studied in the lipopolysaccharide (LPS)-induced macrophage cell line and compared to that of the parent drug DCF using western blot analysis and it was found that the active drug resulted in pronounced inhibition of COX-2 in a dose-dependent manner. Finally, the anti-inflammatory potential of the prodrug and the turn-on fluorescence were validated in the inflammation-induced Wister rat models.

Biocompatible arabinogalactan-chitosan scaffolds for photothermal pharmacology in wound healing and tissue regeneration.

Delayed wound healing is often caused by bacterial infections and persistent inflammation. Multifunctional materials with anti-bacterial, anti-inflammatory, and hemostatic properties are crucial for accelerated wound healing. In this study, we report a biomacromolecule-based scaffold (ArCh) by uniquely combining arabinogalactan (Ar) and chitosan (Ch) using a Schiff-based reaction. Further, the optimized ArCh scaffolds were loaded with Glycyrrhizin (GA: anti-inflammatory molecule) conjugated NIR light-absorbing Copper sulfide (CuS) nanoparticles. The resultant GACuS ArCh scaffolds were characterized for different wound healing parameters in in-vitro and in-vivo models. Our results indicated that GACuS ArCh scaffolds showed excellent swelling, biodegradation, and biocompatibility in vitro. Further results obtained indicated that GACuS ArCh scaffolds demonstrated mild hyperthermia and enhanced hemostatic, anti-oxidant, anti-bacterial, and wound-healing effects when exposed to NIR light. The scaffolds, upon further validation, may be beneficial in accelerating wound healing and tissue regeneration response.

Association of COVID-19 with Comorbidities: An Update.

Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which was identified in Wuhan, China in December 2019 and jeopardized human lives. It spreads at an unprecedented rate worldwide, with serious and still-unfolding health conditions and economic ramifications. Based on the clinical investigations, the severity of COVID-19 appears to be highly variable, ranging from mild to severe infections including the death of an infected individual. To add to this, patients with comorbid conditions such as age or concomitant illnesses are significant predictors of the disease's severity and progression. SARS-CoV-2 enters inside the host cells through ACE2 (angiotensin converting enzyme2) receptor expression; therefore, comorbidities associated with higher ACE2 expression may enhance the virus entry and the severity of COVID-19 infection. It has already been recognized that age-related comorbidities such as Parkinson's disease, cancer, diabetes, and cardiovascular diseases may lead to life-threatening illnesses in COVID-19-infected patients. COVID-19 infection results in the excessive release of cytokines, called "cytokine storm", which causes the worsening of comorbid disease conditions. Different mechanisms of COVID-19 infections leading to intensive care unit (ICU) admissions or deaths have been hypothesized. This review provides insights into the relationship between various comorbidities and COVID-19 infection. We further discuss the potential pathophysiological correlation between COVID-19 disease and comorbidities with the medical interventions for comorbid patients. Toward the end, different therapeutic options have been discussed for COVID-19-infected comorbid patients.

Bio-nanoconjugates of lithocholic acid/IR 780 for ROS-mediated apoptosis and optoacoustic imaging applications in breast cancer.

A new lithocholic acid/IR 780 conjugate (LIC) was designed and synthesized for theranostic applications in triple-negative breast cancer. Lithocholic acid is an antitumor biomacromolecule and acts via multiple molecular targets. IR 780 iodide is a fluorescent NIR organic dye researched as a photothermal agent in cancer therapy. A combined conjugate, LIC can have wide applications as a Photothermal/chemotherapeutic and imaging agent in cancer therapy. LIC was characterized and evaluated for its photothermal cytotoxic effect in breast cancer cell lines. Further, to improve the bioavailability of the LIC, a polymeric (PLGA) nanosystem was developed and characterized. The resultant lithocholic acid/IR 780 polymeric nanoconjugates (LIPNCs) were well taken up by the cells and are evident by the inherent red fluorescence of LIC. The LIPNCs also exhibited commendable heat generation when exposed to NIR light (808 nm). The in-vitro anti-cancer studies of LIPNCs also revealed a significant NIR light-based photothermal efficacy (cytotoxic dose 0.75 µM) when compared to the free conjugate (LIC) or the parent moieties. Further cell-based fluorescent and molecular assays showed that LIPNCs induced ROS-mediated apoptotic cell death concurrently being physiologically biocompatible. In-vitro photoacoustic imaging of the LICs exhibited signals comparable to free IR780 dye. Future in vivo studies with LIPNCs or LIC may prove beneficial for developing a promising translational system for its wide application in image-guided cancer theranostics.

Chlorogenic Acid: a Polyphenol from Coffee Rendered Neuroprotection Against Rotenone-Induced Parkinson's Disease by GLP-1 Secretion.

Parkinson's disease (PD) is a chronic motor disorder, characterized by progressive loss of dopaminergic neurons. Numerous studies suggest that glucagon-like peptide-1 (GLP-1) secretagogue has a neuroprotective role in PD models. The present study evaluated potential of coffee bioactive compounds in terms of their ability to bind GPR-40/43 and tested the neuroprotective effect of best candidate on rotenone-induced PD mice acting via GLP-1 release. In silico molecular docking followed by binding free energy calculation revealed that chlorogenic acid (CGA) has a strong binding affinity for GPR-40/43 in comparison to other bioactive polyphenols. Molecular dynamics simulation studies revealed stable nature of GPR40-CGA and GPR43-CGA interaction and also provided information about the amino acid residues involved in binding. Subsequently, in vitro studies demonstrated that CGA-induced secretion of GLP-1 via enhancing cAMP levels in GLUTag cells. Furthermore, in vivo experiments utilizing rotenone-induced mouse model of PD revealed a significant rise in plasma GLP-1 after CGA administration (50 mg/kg, orally for 13 weeks) with concomitant increase in colonic GPR-40 and GPR-43 mRNA expression. CGA treatment also prevented rotenone-induced motor and cognitive impairments and significantly restored the rotenone-induced oxidative stress. Meanwhile, western blot results confirmed that CGA treatment downregulated rotenone-induced phosphorylated alpha-synuclein levels by upregulating PI3K/AKT signaling and inactivating GSK-3ß through the release of GLP-1. CGA treatment ameliorated rotenone-induced dopaminergic nerve degeneration and alpha-synuclein accumulation in substantia nigra and augmented mean density of dopaminergic nerve fibers in striatum. These findings demonstrated novel biological function of CGA as a GLP-1 secretagogue. An increase in endogenous GLP-1 may render neuroprotection against a rotenone mouse model of PD and has the potential to be used as a neuroprotective agent in management of PD.

Nutraceutical prospects of Houttuynia cordata against the infectious viruses.

The novel enveloped ß-coronavirus SARS-CoV-2 (COVID-19) has offered a surprising health challenge all over the world. It develops severe pneumonia leading to acute respiratory distress syndrome (ARDS). Like SARS-COV-2, other encapsulated viruses like HIV, HSV, and influenza have also offered a similar challenge in the past. In this regard, many antiviral drugs are being explored with varying degrees of success to combat the associated pathological conditions. Therefore, upon scientific validation & development, these antiviral phytochemicals can attain a futuristic nutraceutical prospect in managing different encapsulated viruses. Houttuynia cordata (HC) is widely reported for activities such as antioxidant, anti-inflammatory, and antiviral properties. The major antiviral bioactive components of HC include essential oils (methyl n-nonyl ketone, lauryl aldehyde, capryl aldehyde), flavonoids (quercetin, rutin, hyperin, quercitrin, isoquercitrin), and alkaloids (norcepharadione B) & polysaccharides. HC can further be explored as a potential nutraceutical agent in the therapy of encapsulated viruses like HIV, HSV, and influenza. The review listed various conventional and green technologies that are being employed to extract potent phytochemicals with diverse activities from the HC. It was indicated that HC also inhibited molecular targets like 3C-like protease (3CLPRO) and RNA-dependent RNA polymerase (RdRp) of COVID-19 by blocking viral RNA synthesis and replication. Antioxidant and hepatoprotective effects of HC have been evident in impeding complications from marketed drugs during antiviral therapies. The use of HC as a nutraceutical is localized within some parts of Southeast Asia. Further technological advances can establish it as a nutraceutical-based functional food against pathogenic enveloped viruses like COVID 19.