Natural Medicine a Promising Candidate in Combating Microbial Biofilm.

Studies on biofilm-related infections are gaining prominence owing to their involvement in most clinical infections and seriously threatening global public health. A biofilm is a natural form of bacterial growth ubiquitous in ecological niches, considered to be a generic survival mechanism adopted by both pathogenic and non-pathogenic microorganisms and entailing heterogeneous cell development within the matrix. In the ecological niche, quorum sensing is a communication channel that is crucial to developing biofilms. Biofilm formation leads to increased resistance to unfavourable ecological effects, comprising resistance to antibiotics and antimicrobial agents. Biofilms are frequently combated with modern conventional medicines such as antibiotics, but at present, they are considered inadequate for the treatment of multi-drug resistance; therefore, it is vital to discover some new antimicrobial agents that can prevent the production and growth of biofilm, in addition to minimizing the side effects of such therapies. In the search for some alternative and safe therapies, natural plant-derived phytomedicines are gaining popularity among the research community. Phytomedicines are natural agents derived from natural plants. These plant-derived agents may include flavonoids, terpenoids, lectins, alkaloids, polypeptides, polyacetylenes, phenolics, and essential oils. Since they are natural agents, they cause minimal side effects, so could be administered with dose flexibility. It is vital to discover some new antimicrobial agents that can control the production and growth of biofilms. This review summarizes and analyzes the efficacy characteristics and corresponding mechanisms of natural-product-based antibiofilm agents, i.e., phytochemicals, biosurfactants, antimicrobial peptides, and their sources, along with their mechanism, quorum sensing signalling pathways, disrupting extracellular matrix adhesion. The review also provides some other strategies to inhibit biofilm-related illness. The prepared list of newly discovered natural antibiofilm agents could help in devising novel strategies for biofilm-associated infections.

In Vitro and In Vivo Investigation of a Dual-Targeted Nanoemulsion Gel for the Amelioration of Psoriasis.

Psoriasis, due to its unique pathological manifestations and the limited success of existing therapeutic modalities, demands dedicated domain research. Our group has developed nanotherapeutics consisting of bioactives such as Thymoquinone (TQ) and Fulvic acid (FA), which have been successfully incorporated into a Nanoemulsion gel (NEG), taking kalonji oil as oil phase. The composition is aimed at ameliorating psoriasis with better therapeutic outcomes. TQ is a natural bio-active that has been linked to anti-psoriatic actions. FA has anti-inflammatory actions due to its free radical and oxidant-scavenging activity. Our previous publication reports the formulation development of the NEG, where we overcame the pharmaco-technical limitations of combining the above two natural bioactives. In vitro evaluation of the optimized NEG was carried out, which showed an enhanced dissolution rate and skin permeation of TQ. This work furthers the pharmaceutical progression of dual-targeted synergistic NEG to treat psoriasis. A suitable animal model, BALB/c mice, has been used to conduct the in vivo studies, which revealed the effective anti-psoriatic action of TQ. Molecular docking studies corroborated the results and revealed a good binding affinity for both the targets of TNF-α (Tumor necrosis factor) and IL-6 (Interlukin-6). Tissue uptake by Confocal laser scanning microscopy (CLSM), a skin interaction study of the gel formulation, and an antioxidant free radical scavenging assay (1-1 Diphenyl-2-picrylhydrazyl DPPH) were also carried out. It was concluded that the NEG may be effective in treating psoriasis with minimal side effects.

The profile of HSPA1A gene expression and its association with heat tolerance in crossbred cattle and the tropically adapted dwarf Vechur and Kasaragod.

Certain livestock breeds are adapted to hot and humid environments, and these breeds have genetics that could be useful in a changing climate. The expression of several genes has been identified as a useful biomarker for heat stress. In this study, the responses to heat exposure of heat-tolerant Vechur and Kasaragod cattle found in Kerala state in India (also known as dwarf Bos taurus indicus) were compared to crossbred cattle (crosses of Bos t. taurus with Bos t. indicus). At various time points during heat exposure, rectal temperature and the expression of HSPA1A were determined, and the relationship between them was characterized. We characterized HSPA1A mRNA in Vechur cattle and performed molecular clock analysis. The expression of HSPA1A between the lineages and at different temperature humidity index (THI) was significant. There were significant differences between the expression profiles of HSPA1A in Kasaragod and crossbred (p < 0.01) and Vechur and crossbred (p < 0.01) cattle, but no significant difference in expression was observed between Vechur and Kasaragod cattle. The genetic distance between Vechur, B. grunniens, B. t. taurus, and B. t. indicus was 0.0233, 0.0059, and 0.007, respectively. The genetic distance between Vechur and the Indian dwarf breed Malnad Gidda was 0.0081. A molecular clock analysis revealed divergent adaptive evolution of Vechur cattle to B. t. taurus, with adaptations to the high temperatures and humidity that are prevalent in their breeding tract in Kerala, India. These results could also prove useful in selecting heat-tolerant animals using HSPA1A as a marker.

The anti-inflammatory properties of the methanolic extract of Cucumis melo Linn. against prostate enlargement in Wistar rats.

In different parts of the world, Cucumis melo Linn. (C melo) is used for its medicinal properties. The present study examined the effects of a methanolic extract of C melo Linn. (F1 hybrid, MECM) on benign prostatic hyperplasia in adult male Wistar rats and evaluated its anti-inflammatory activity in vivo. MECM treatment reduced prostate weight mildly. Histopathological studies showed that the extract produced a strong protective effect against the development of BPH by testosterone. The MECM also showed protection from testosterone-induced benign prostatic hyperplasia (BPH). MECM was tested against carrageenan-induced inflammation in rats' paws to determine its anti-inflammatory activity. It was shown that MECM had a pronounced effect on the inflammatory response in the late phase, i.e., one hour after carrageenan injection. Prostaglandins and nitric oxide are primarily responsible for this phase indicating that MECM can modify the production and release of prostaglandin and nitric oxide. A novel formulation containing C melo may be able to treat the conditions mentioned above.

Quorum-sensing molecules: Sampling, identification and characterization of N-acyl-homoserine lactone in Vibrio sp.

Quorum sensing (QS) is a mechanism by which gram-negative bacteria regulate their gene expression by making use of cell density. QS is triggered by a small molecule known as an autoinducer. Typically, gram-negative bacteria such as Vibrio produce signaling molecules called acyl homoserine lactones (AHLs). However, their levels are very low, making them difficult to detect. We used thin layer chromatography (TLC) to examine AHLs in different Vibrio species, such as Vibrio alginolyticus, Vibrio parahemolyticus, and Vibrio cholerae, against a standard- Chromobacterium violaceum. Further, AHLs were characterised by high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). C4-HSL (N- butanoyl- L- homoserine lactone), C6-HSL (N- hexanoyl- L- homoserine lactone), 3-oxo-C8-HSL (N-(3-Oxooctanoyl)-DL-homoserine lactone), C8-HSL (N- octanoyl- L- homoserine lactone), C110-HSL (N- decanoyl- L- homoserine lactone), C12-HSL (N- dodecanoyl- L- homoserine lactone) and C14-HSL (N- tetradecanoyl- L- homoserine lactone) were identified from Vibrio. These results may provide a basis for blocking the AHL molecules of Vibrio, thereby reducing their pathogenicity and eliminating the need for antimicrobials.

Therapeutic potential of induced iron depletion using iron chelators in Covid-19.

Ferritin, which includes twenty-four light and heavy chains in varying proportions in different tissues, is primarily responsible for maintaining the body's iron metabolism. Its normal value is between 10 and 200 ngmL-1 in men and between 30 and 300 ngmL-1 in women. Iron is delivered to the tissue via them, and they act as immunomodulators, signaling molecules, and inflammatory markers. When ferritin level exceeds 1000 µgL-1, the patient is categorized as having hyperferritinemia. Iron chelators such as deferiprone, deferirox, and deferoxamine are currently FDA approved to treat iron overload. The inflammation cascade and poor prognosis of COVID-19 may be attributed to high ferritin levels. Critically ill patients can benefit from deferasirox, an iron chelator administered orally at 20-40 mgkg-1 once daily, as well as intravenous deferoxamine at 1000 mg initially followed by 500 mg every 4 to 12 h. It can be combined with monoclonal antibodies, antioxidants, corticosteroids, and lactoferrin to make iron chelation therapy effective for COVID-19 victims. In this article, we analyze the antiviral and antifibrotic activity of iron chelators, thereby promoting iron depletion therapy as a potentially innovative treatment strategy for COVID-19.

Clustering of COVID-19 data for knowledge discovery using c-means and fuzzy c-means.

In this work, the partitioning clustering of COVID-19 data using c-Means (cM) and Fuzy c-Means (Fc-M) algorithms is carried out. Based on the data available from January 2020 with respect to location, i.e., longitude and latitude of the globe, the confirmed daily cases, recoveries, and deaths are clustered. In the analysis, the maximum cluster size is treated as a variable and is varied from 5 to 50 in both algorithms to find out an optimum number. The performance and validity indices of the clusters formed are analyzed to assess the quality of clusters. The validity indices to understand all the COVID-19 clusters' quality are analysed based on the Zahid SC (Separation Compaction) index, Xie-Beni Index, Fukuyama-Sugeno Index, Validity function, PC (performance coefficient), and CE (entropy) indexes. The analysis results pointed out that five clusters were identified as a major centroid where the pandemic looks concentrated. Additionally, the observations revealed that mainly the pandemic is distributed easily at any global location, and there are several centroids of COVID-19, which primarily act as epicentres. However, the three main COVID-19 clusters identified are 1) cases with value <50,000, 2) cases with a value between 0.1 million to 2 million, and 3) cases above 2 million. These centroids are located in the US, Brazil, and India, where the rest of the small clusters of the pandemic look oriented. Furthermore, the Fc-M technique seems to provide a much better cluster than the c-M algorithm.