Medicinal Plants as Therapeutic Alternatives to Combat Mycobacterium tuberculosis: A Comprehensive Review.

Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis (MTB) and a significant health concern worldwide. The main threat to the elimination of TB is the development of resistance by MTB to the currently used antibiotics and more extended treatment methods, which is a massive burden on the health care system. As a result, there is an urgent need to identify new, effective therapeutic strategies with fewer adverse effects. The traditional medicines found in South Asia and Africa have a reservoir of medicinal plants and plant-based compounds that are considered another reliable option for human beings to treat various diseases. Abundant research is available for the biotherapeutic potential of naturally occurring compounds in various diseases but has been lagging in the area of TB. Plant-based compounds, or phytoproducts, are being investigated as potential anti-mycobacterial agents by reducing bacterial burden or modulating the immune system, thereby minimizing adverse effects. The efficacy of these phytochemicals has been evaluated through drug delivery using nanoformulations. This review aims to emphasize the value of anti-TB compounds derived from plants and provide a summary of current research on phytochemicals with potential anti-mycobacterial activity against MTB. This article aims to inform readers about the numerous potential herbal treatment options available for combatting TB.

Polyester nanomedicines targeting inflammatory signaling pathways for cancer therapy.

The growth of cancerous cells and their responses towards substantial therapeutics are primarily controlled by inflammations (acute and chronic) and inflammation-associated products, which either endorse or repress tumor progression. Additionally, major signaling pathways, including NF-κB, STAT3, inflammation-causing factors (cytokines, TNF-α, chemokines), and growth-regulating factors (VEGF, TGF-ß), are vital regulators responsible for the instigation and resolution of inflammations. Moreover, the conventional chemotherapeutics have exhibited diverse limitations, including poor pharmacokinetics, unfavorable chemical properties, poor targetability to the disease-specific disease leading to toxicity; thus, their applications are restricted in inflammation-mediated cancer therapy. Furthermore, nanotechnology has demonstrated potential benefits over conventional chemotherapeutics, such as it protected the incorporated drug/bioactive moiety from enzymatic degradation within the systemic circulation, improving the physicochemical properties of poorly aqueous soluble chemotherapeutic agents, and enhancing their targetability in specified carcinogenic cells rather than accumulating in the healthy cells, leading reduced cytotoxicity. Among diverse nanomaterials, polyester-based nanoparticulate delivery systems have been extensively used to target various inflammation-mediated cancers. This review summarizes the therapeutic potentials of various polyester nanomaterials (PLGA, PCL, PLA, PHA, and others)-based delivery systems targeting multiple signaling pathways related to inflammation-mediated cancer.

Bio-fabrication of Bio-inspired Silica Nanomaterials from Bryophyllum pinnatum Leaf for Agricultural Applications.

A green chemistry approach was employed to synthesize silica nanoparticles (SiNPs) using aqueous extract of Bryophyllum pinnatum leaf as capping agents. The novelty of this study was to produce silica nanoparticles using the biological method. An analysis of the physicochemical properties of formed nanoparticles was successfully completed through sophisticated characterization methods, such as UV-Visible absorbance spectroscopy, Fourier transform infra-red spectroscopy, X-ray diffraction, scanning electron microscope, energy dispersive X-ray, zeta potential analysis, and thermo-gravimetric analysis. All the characterization results indicated their spherical morphology and amorphous nature with an average size of 24 nm. FT-IR results highlighted the key bioactive compounds that could be responsible for capping and reducing the formation of SiNPs. Synthesized SiNPs show excellent stability with a negative zeta potential value of - 32 mV. The biomolecules from B. pinnatum were successfully working for the formation of Si NPs with spherical shapes. Moreover, to assess the agricultural application, green-synthesized SiNPs were carried out by seed germination assay on Vigna radiata. The seed germination assay confirms that a low concentration of SiNPs enhances seed germination. Meanwhile, a higher concentration of the SiNPs inhibits seed germination and shoot, and root formation. SiNPs at optimum concentration could be used in the agriculture field as nano growth promoters.

Re-establishing the comprehension of phytomedicine and nanomedicine in inflammation-mediated cancer signaling.

Recent mounting evidence has revealed extensive genetic heterogeneity within tumors that drive phenotypic variation affecting key cancer pathways, making cancer treatment extremely challenging. Diverse cancer types display resistance to treatment and show patterns of relapse following therapy. Therefore, efforts are required to address tumor heterogeneity by developing a broad-spectrum therapeutic approach that combines targeted therapies. Inflammation has been progressively documented as a vital factor in tumor advancement and has consequences in epigenetic variations that support tumor instigation, encouraging all the tumorigenesis phases. Increased DNA damage, disrupted DNA repair mechanisms, cellular proliferation, apoptosis, angiogenesis, and its incursion are a few pro-cancerous outcomes of chronic inflammation. A clear understanding of the cellular and molecular signaling mechanisms of tumor-endorsing inflammation is necessary for further expansion of anti-cancer therapeutics targeting the crosstalk between tumor development and inflammatory processes. Multiple inflammatory signaling pathways, such as the NF-κB signaling pathway, JAK-STAT signaling pathway, MAPK signaling, PI3K/AKT/mTOR signaling, Wnt signaling cascade, and TGF-ß/Smad signaling, have been found to regulate inflammation, which can be modulated using various factors such as small molecule inhibitors, phytochemicals, recombinant cytokines, and nanoparticles (NPs) in conjugation to phytochemicals to treat cancer. Researchers have identified multiple targets to specifically alter inflammation in cancer therapy to restrict malignant progression and improve the efficacy of cancer therapy. siRNA-and shRNA-loaded NPs have been observed to downregulate STAT3 signaling pathways and have been employed in studies to target tumor malignancies. This review highlights the pathways involved in the interaction between tumor advancement and inflammatory progression, along with the novel approaches of nanotechnology-based drug delivery systems currently used to target inflammatory signaling pathways to combat cancer.

Aptameric nanobiosensors for the diagnosis of COVID-19: An update.

COVID-19 pandemic has left a catastrophic effect on the world economy and human civilization. As an effective step towards controlling the transmission of viral infections during multiple waves of COVID-19, there is an urgent need to develop robust nanobiosensors for the detection of SARS-CoV-2 with high sensitivity, specificity, and fast analysis. Aptameric nanobiosensors are rapid and sensitive diagnostic platforms, capable of SARS-CoV-2 detection, which overcomes the limitations of the conventional techniques. This review article presents an outline of the aptameric nanobiosensors established for improved diagnosis of SARS-CoV-2 and the future perspectives are also covered.

Phytomedicines Targeting Cancer Stem Cells: Therapeutic Opportunities and Prospects for Pharmaceutical Development.

The presence of small subpopulations of cells within tumor cells are known as cancer stem cells (CSCs). These cells have been the reason for metastasis, resistance with chemotherapy or radiotherapy, and tumor relapse in several types of cancers. CSCs underwent to epithelial-mesenchymal transition (EMT) and resulted in the development of aggressive tumors. CSCs have potential to modulate numerous signaling pathways including Wnt, Hh, and Notch, therefore increasing the stem-like characteristics of cancer cells. The raised expression of drug efflux pump and suppression of apoptosis has shown increased resistance with anti-cancer drugs. Among many agents which were shown to modulate these, the plant-derived bioactive agents appear to modulate these key regulators and were shown to remove CSCs. This review aims to comprehensively scrutinize the preclinical and clinical studies demonstrating the effects of phytocompounds on CSCs isolated from various tumors. Based on the available convincing literature from preclinical studies, with some clinical data, it is apparent that selective targeting of CSCs with plants, plant preparations, and plant-derived bioactive compounds, termed phytochemicals, may be a promising strategy for the treatment of relapsed cancers.

Emerging insights into mitochondria-specific targeting and drug delivering strategies: Recent milestones and therapeutic implications.

Mitochondria are a major intracellular organelle for drug targeting due to its functional roles in cellular metabolism and cell signaling for proliferation and cell death. Mitochondria-targeted treatment strategy could be promising to improve the therapeutic efficacy of cancer while minimizing the adverse side effects. Over the last decades, several studies have explored and focused on mitochondrial functions, which has led to the emergence of mitochondria-specific therapies. Molecules in the mitochondria are considered to be prime targets, and a wide range of molecular strategies have been designed for targeting mitochondria compared with that of the cytosol. In this review, we focused on the molecular mechanisms of mitochondria-specific ligand targeting and selective drug action strategies for targeting mitochondria, including those premised on mitochondrial targeting of signal peptides (MTS), cell-penetrating peptides (CPPs), and use of lipophilic cations. Furthermore, most research has concentrated on specific conjugation of ligands to therapeutic molecules to enhance their effectiveness. There are several variations for the ideal design and development for mitochondrial-targeted drugs, such as selecting a suitable ligand and linker targets. However, some challenges related to drug solubility and selectivity could be resolved using the nanocarrier system. Nanoparticles yield excellent advantages for targeting and transmitting therapeutic drugs, and they offer elegant platforms for mitochondria-specific drug delivery. We explain many of the advanced and proven strategies for multifunctional mitochondria-specific targets, which should contribute to achieving better anticancer therapies in a promising future.

Identification and Characterization of a Newly Isolated Chitinase-Producing Strain Bacillus licheniformis SSCL-10 for Chitin Degradation.

Chitinases or chitinolytic enzymes have different applications in the field of medicine, agriculture, and industry. The present study is aimed at developing an effective hyperchitinase-producing mutant strain of novel Bacillus licheniformis. A simple and rapid methodology was used for screening potential chitinolytic microbiota by chemical mutagenesis with ethylmethane sulfonate and irradiation with UV. There were 16 mutant strains exhibiting chitinase activity. Out of the chitinase-producing strains, the strain with maximum chitinase activity was selected, the protein was partially purified by SDS-PAGE, and the strain was identified as Bacillus licheniformis (SSCL-10) with the highest specific activity of 3.4 U/mL. The induced mutation model has been successfully implemented in the mutant EMS-13 (20.2 U/mL) that produces 5-6-fold higher yield of chitinase, whereas the mutant UV-11 (13.3 U/mL) has 3-4-fold greater chitinase activity compared to the wild strain. The partially purified chitinase has a molecular weight of 66 kDa. The wild strain (SSCL-10) was identified as Bacillus licheniformis using 16S rRNA sequence analysis. This study explores the potential applications of hyperchitinase-producing bacteria in recycling and processing chitin wastes from crustaceans and shrimp, thereby adding value to the crustacean industry.

Protective effect of leaf extract of Abutilon indicum on DNA damage and peripheral blood lymphocytes in combating the oxidative stress.

The current research explores in vitro antioxidant characteristics, radiation-induced DNA damage protection and quenching effects of the oxidative stress by the ethanolic leaf extract of Abutilon indicum (EEAI) on human peripheral blood lymphocytes (PBLs). PBLs were incubated with various concentrations of EEAI accompanied by pre- and post-treatment with hydrogen peroxide. Cell viability was investigated by MTT assay. In addition, quenching of free radicals were measured in vitro using DPPH, superoxide anion, hydrogen peroxide, reducing power and nitric oxide radical scavenging assays. These activities were compared with ascorbic acid as standard antioxidants. Furthermore, inhibition of UV radiation-induced strand break formation in plasmid pBR322 DNA and anti-Fenton reactions in calf thymus DNA was evaluated. Cytotoxic effects of hydrogen peroxide on PBLs were significantly reduced with EEAI pre-treatment compared to post-treatment in a dose-dependent manner comparable with similar cytoprotective effects of ascorbic acid (p > 0.05). EEAI has shown strong antioxidant effects in the scavenging of DPPH, superoxide anion, hydrogen peroxide, and nitric oxide. EEAI also has a strong protective effect of UV-induced plasmid pBR322 DNA cleavage and Fenton-induced DNA damage. Overall, the results revealed that Abutilon indicum has a cytoprotective, potent antioxidant and DNA protective effect that provide pharmacological credence to justify its overall biological activity. Furthermore, future studies to identifying bioactive molecules and its molecular mechanisms responsible for promising therapeutic applications in the rescue of disease-induced cellular oxidative damage.

Phytochemical characteristics of aerial part of Cissus quadrangularis (L) and its in-vitro inhibitory activity against leukemic cells and antioxidant properties.

BACKGROUND AND OBJECTIVES: Cissus quadrangularis Linn, is a rich bioresource for folk and traditional medicines from ancient times till date. The present study aimed to investigate the free radical scavenging and anticancer efficacy in vitro of the ethanolic and methanolic extract from the aerial parts of Cissus quadrangularis (L). MATERIAL AND METHODS: In vitro cell-free antioxidant analyses were performed for the ethanolic extract of Cissus quadrangularis (L). (EECQ) and methanolic extract of Cissus quadrangularis (L). (MECQ) using different free radical scavenging assays includes DPPH, nitric oxide, superoxide, metal chelation, and hydrogen peroxide radical scavenging assays. In vitro leukemic cytotoxic assessment by MTT assay was performed both EECQ and MECQ extract against HL-60 cell lines. RESULTS: Strong antioxidant effects were recorded in EECQ and MECQ in all the cell-free models. The ethanolic extract exhibited a significant dose-dependent free radical activity in comparison with methanolic extracts. The EECQ and MECQ possess pronounced anticancer efficacy against leukemic cells HL-60 with an IC50 value of 36 µg/mL and 40 µg/mL respectively. CONCLUSION: Present data indicates the presence of marked antioxidant and anticancer behaviors in the extracts of aerial portions of Cissus quadrangularis (L). extracts. Thus, Cissus quadrangularis (L). poses as a promising safe chemopreventive plant to combat cancer.

Evaluation of in vitro activities of extracellular enzymes from Aspergillus species isolated from corneal ulcer/keratitis.

Mycotic/fungal keratitis is a suppurative, generally ulcerative infection of the cornea. The filamentous fungi, Aspergillus spp. are the second leading cause of mycotic keratitis, particularly in India. Aspergillus spp. produce a range of extracellular enzymes that are used to break down complex molecules and used for growth and reproduction, also for survival on/in host organism. The current study was designed with an objective to screen in vitro extracellular enzyme activity of Fusarium and Aspergillus isolates from mycotic keratitis patients and to correlate the same as a putative virulence factor. Extracellular enzymes viz., deoxyribonuclease (DNase), protease, lipase, elastase, keratinase, etc., produced by Aspergillus have key role in keratomycosis and hence their (n = 85) in vitro activities were investigated. It was found that, the majority of the Aspergillus isolates produced protease (n = 75; 88% of 85) followed by lipase (n = 59; 69% of 85), DNase (n = 35; 41% of 85), elastase (n = 26; 31% of 85) and keratinase (n = 13; 15% of 85). The enzyme activity indices (EAI) for DNase, elastase, protease and lipase ranged between 1.01 and 1.98, whereas elastase EAI varied between 1.26 and 1.92. DNase, protease and lipase showed a maximum EAI of 1.98 and lowest EAI value of 1.01, respectively. Extracellular enzymes of Aspergillus spp. may have potential role in the onset and progression of keratitis.

Footprint of the COVID-19 Pandemic in India: A Study of Immune Landscape and Other Factors Shielding Mortality.

The impact of the SARS-CoV-2 pandemic has significantly affected global health and created a world crisis. The exponentially increasing numbers of infection and mortality have made preventive measures challenging. India being a highly populated nation has so far effectively counteracted the pandemic outbreak with a significantly lower rate of mortality despite the high infection rates. The genetic architecture of the immune response genes in the Indian population, BCG vaccination, the predominantly young age group of people, and their traditional food habits might contribute to the lower rate of mortality. Human leukocyte antigens (HLA) play a vital role in triggering T cells, and natural killer (NK) cells can immediately react to eliminate infected cells. Activation of virus-specific CD4+ T cells and CD8+ cytotoxic T cells selectively targets the infected cells and strengthens the immunoregulatory system. The checkpoint for NK cell function is the engagement of killer Ig-like receptors (KIR) molecules with their respective HLA ligands overexpressed or expressed on the compromised virus-infected cells which have shown polymorphism among different ethnic groups. Here, we explore if certain KIR-HLA motifs grant Indians a survival advantage in terms of the low rate of mortality. Additionally, enhanced immunity through BCG vaccination may favor fruitful eradication of SARS-CoV-2 and provide the way out as in therapeutic intervention and vaccination strategies.

Augmented cytotoxic effects of paclitaxel by curcumin induced overexpression of folate receptor-α for enhanced targeted drug delivery in HeLa cells.

BACKGROUND: New targeted therapies are intended to minimize the toxic effects and maximize destruction of tumor cells. Folate is a membrane-bound receptor that plays a vital role in the uptake of anti-folate molecules aimed for efficient drug delivery of anti-folate drugs. PURPOSE: The present study is aimed at the modulation of the expression of folate receptor by curcumin that enhances the intake, cytotoxicity and anticancer effects of paclitaxel in HeLa cells. MATERIALS AND METHODS: HeLa cells were pretreated with curcumin and treated with paclitaxel. We measured the cell viability, uptake of radiolabelled folic acid and paclitaxel, Folate receptor -alpha (FR-α) protein expression by immunocytochemistry and western blot and FR-α mRNA expression by qualitative and quantitative analysis. RESULTS: This study shows that curcumin (10 - 50 µM) causes significantly increased cytotoxicity in a dose and time dependent manner. It also enhances the intake of radiolabeled folic acid and paclitaxel 3-4 folds in HeLa cells. The pretreatment of HeLa cells with curcumin shows statistically significant of cell death by paclitaxel. The quantitative RT-PCR demonstrates the expression of FR- α mRNA upon curcumin treatment. Furthermore, immunochemistry and western blotting analysis proved that curcumin enhances expression the FR- α in HeLa cells. CONCLUSION: Our study proved that the molecular mechanism of curcumin enhances the upregulation of FR - α mRNA and protein expression in HeLa cells. Therefore, a combination of curcumin and paclitaxel at less concentration may be a targeting strategy for FR-targeted drug delivery providing a better therapeutic intervention of cancer.

Emerging Role of Adipocytokines in Type 2 Diabetes as Mediators of Insulin Resistance and Cardiovascular Disease.

Adipose tissue is an enormously active endocrine organ, secreting various hormones, such as adiponectin, leptin, resistin and visfatin, together with classical cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). All these adipocytokines play significant roles in the regulation of energy metabolism, glucose and lipid metabolism, reproduction, cardiovascular function and immunity. Adipocytokines are significantly regulated by nutritional status and can directly influence other organ systems, including brain, liver and skeletal muscle. Adiponectin plays a key role as an anti-inflammatory hormone. Upregulated expression of resistin, vaspin, apelin and TNF-α plays a significant role in induction of insulin resistance linked with obesity and type 2 diabetes. Ghrelin, the circulating peptide, has been found to stimulate appetite and regulate energy balance. Thus, it can be considered 1 of the candidate genes for obesity and type 2 diabetes. Omentin is a novel adipokine produced by visceral adipose tissue. Circulating levels of omentin are decreased in insulin-resistant states, for example, in obesity and diabetes. IL-6 plays a vital role in regulating the accumulation of lipids intramyocardially. Based on the biologic relevance of these adipocytokines, they can no longer be considered as energy storage sites alone but must also be considered in metabolic control. Hence, the present review summarizes the regulatory roles of adipocytokines in diabetes linked with obesity.

An efficient protocol for deriving liver stem cells from neonatal mice: validating its differentiation potential.

The success of liver regeneration depends on the availability of suitable cell types and their potential to differentiate into functional hepatocytes. To identify the stem cells which have the ability to differentiate into hepatocytes, we used neonatal liver as source. However, the current protocol for isolating stem cells from liver involves enzymes like collagenase, hyaluronidase exposed for longer duration which limits the success. This results in the keen interest to develop an easy single step enzyme digestion protocol for isolating stem cells from liver for tissue engineering approaches. Thus, the unlimited availability of cell type favors setting up the functional recovery of the damaged liver, ensuring ahead success towards treating liver diseases. We attempted to isolate liver stem derived cells (LDSCs) from mouse neonatal liver using single step minimal exposure to enzyme followed by in vitro culturing. The cells isolated were characterized for stem cell markers and subjected to lineage differentiation. Further, LDSCs were induced to hepatocyte differentiation and validated with hepatocyte markers. Finally, we developed a reproducible, efficient protocol for isolation of LDSCs with functional hepatocytes differentiation potential, which further can be used as in vitro model system for assessing drug toxicity assays in various preclinical trials.

Augmented sensitivity to methotrexate by curcumin induced overexpression of folate receptor in KG-1 cells.

Folate receptors are targets of various strategies aimed at efficient delivery of anti-cancer drugs. Folate receptors also play a role in the uptake of antifolate drugs which are used for therapeutic intervention in leukemia. Therefore, it is important to identify compounds which regulate expression of folate receptors in leukemic cells. The present study examined if curcumin could modulate the uptake and cytotoxicity of the antifolate drug methotrexate, in KG-1 leukemic cells. This is the first report to show that curcumin (10-50 µM) causes a significant, dose-dependent, 2-3 fold increase in uptake of radiolabelled folic acid and methotrexate into KG-1 cells both at 24 h and 48 h of treatment. Interestingly, pre-treatment of KG-1 leukemic cells with curcumin (10 µM and 25 µM) also caused a statistically significant enhancement in the cytotoxicity of methotrexate. We performed Real Time Quantitative RT-PCR to confirm the upregulation of FRß mRNA in curcumin treated cells. Immunocytochemistry and Western blotting showed that curcumin caused increased expression of folate receptor ßin KG-1 cells. Our data show that the mechanism of curcumin action involves up-regulation of folate receptor ß mRNA and protein in KG-1 cells. Therefore, combination of non-toxic concentrations of curcumin and methotrexate, may be a viable strategy for therapeutic intervention for leukemias using a folate receptor-targeted drug delivery system.