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Rheumatoid arthritis: Recent advances on its etiology, role of cytokines and pharmacotherapy

Alam J, Jantan I, Bukhari SNA

Biomed Pharmacother, 2017 Aug;92:615-633.
PMID: 28582758 DOI: 10.1016/j.biopha.2017.05.055

An autoimmune disease is defined as a clinical syndrome resulted from an instigation of both T cell and B cell or individually, in the absence of any present infection or any sort of distinguishable cause. Clonal deletion of auto reactive cells remains the central canon of immunology for decades, keeping the role of T cell and B cell aside, which are actually the guards to recognize the entry of foreign body. According to NIH, 23.5 million Americans are all together affected by these diseases. They are rare, but with the exception of RA. Rheumatoid arthritis is chronic and systemic autoimmune response to the multiple joints with unknown ethology, progressive disability, systemic complications, early death and high socioeconomic costs. Its ancient disease with an old history found in North American tribes since 1500 BCE, but its etiology is yet to be explored. Current conventional and biological therapies used for RA are not fulfilling the need of the patients but give only partial responses. There is a lack of consistent and liable biomarkers of prognosis therapeutic response, and toxicity. Rheumatoid arthritis is characterized by hyperplasic synovium, production of cytokines, chemokines, autoantibodies like rheumatoid factor (RF) and anticitrullinated protein antibody (ACPA), osteoclastogensis, angiogenesis and systemic consequences like cardiovascular, pulmonary, psychological, and skeletal disorders. Cytokines, a diverse group of polypeptides, play critical role in the pathogenesis of RA. Their involvement in autoimmune diseases is a rapidly growing area of biological and clinical research. Among the proinflammatory cytokines, IL-1α/β and TNF-α trigger the intracellular molecular signalling pathway responsible for the pathogenesis of RA that leads to the activation of mesenchymal cell, recruitment of innate and adaptive immune system cells, activation of synoviocytes which in term activates various mediators including tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-8 (IL-8), resulting in inflamed synovium, increase angiogenesis and decrease lymphangiogensis. Their current pharmacotherapy should focus on their three phases of progression i.e. prearthritis phase, transition phase and clinical phase. In this way we will be able to find a way to keep the balance between the pro and anti-inflammatory cytokines that is believe to be the dogma of pathogenesis of RA. For this we need to explore new agents, whether from synthetic or natural source to find the answers for unresolved etiology of autoimmune diseases and to provide a quality of life to the patients suffering from these diseases specifically RA.
Suppressive Effects of the Standardized Extract of Phyllanthus amarus on Type II Collagen-induced Rheumatoid Arthritis in Sprague Dawley Rats

Alam J, Jantan I, Kumolosasi E, Nafiah MA, Mesaik MA

Curr Pharm Biotechnol, 2018;19(14):1156-1169.
PMID: 30539691 DOI: 10.2174/1389201020666181211124954

BACKGROUND: Standardized extract of Phyllanthus amarus has been shown to possess inhibitory effects on cellular and humoral immune responses in Wistar-Kyoto rats and Balb/c mice.
OBJECTIVE: In the present study, the standardized extract of P. amarus was investigated for its suppressive effects on type II collagen-induced rheumatoid arthritis (TCIA) in Sprague Dawley rats.
METHOD: The major components of the extracts, lignans and phenolic compounds were analysed by using a validated reversed phase HPLC and LC-MS/MS. A rheumatoid arthritis rat model was induced by administering a bovine type II collagen emulsion subcutaneously at the base of tail, on day 0 and 7 of the experiment. Effects of the extract on severity assessment, changes in the hind paw volume, bone mineral density, body weight and body temperature were measured. Concentrations of cytokines (TNF-α, IL-1β, IL-1α, IL-6) released, matrix metalloproteinases (MMP-1, MMP-3 MMP-9) and their inhibitor (TIMP-1), haematological and biochemical changes were also measured. ELISA was used to measure the cytokines and proteinases in the rat serum and synovial fluid according to manufacturer's instructions.
RESULTS: The extract dose-dependently modulated the progression in physical parameters (i.e. decrease in body weight, increase in body temperature, reduced hind paw volume, reduced the severity of arthritis), bone mineral density, haematological and biochemical perturbations, serum cytokines production and levels of matrix metalloproteinases and their inhibitor in the synovial fluid. Histopathological examination of the knee joint also revealed that the extract effectively reduced synovitis, pannus formation, bone resorption and cartilage destruction.
CONCLUSION: The results suggest that the oral administration of a standardized extract of P. amarus was able to suppress the humoral and cellular immune responses to type II collagen, resulting in the reduction of the development of TCIA in the rats.
Fulltext Suppression of Cisplatin-Induced Vomiting byCannabis sativain Pigeons: Neurochemical Evidences

Ullah I, Subhan F, Alam J, Shahid M, Ayaz M

Front Pharmacol, 2018;9:231.
PMID: 29615907 DOI: 10.3389/fphar.2018.00231

Cannabis sativa
(CS, familyCannabinaceae) has been reported for its anti-emetic activity against cancer chemotherapy-induced emesis in animal models and in clinics. The current study was designed to investigateCSfor potential effectiveness to attenuate cisplatin-induced vomiting in healthy pigeons and to study the impact on neurotransmitters involved centrally and peripherally in the act of vomiting. High-performance liquid chromatography system coupled with electrochemical detector was used for the quantification of neurotransmitters 5-hydroxytryptamine (5HT), dopamine (DA) and their metabolites; Di-hydroxy Phenyl Acetic acid (Dopac), Homovanillic acid (HVA), and 5-hydroxy indole acetic acid (5HIAA) centrally in specific brain areas (area postrema and brain stem) while, peripherally in small intestine. Cisplatin (7 mg/kg i.v.) induce emesis without lethality across the 24 h observation period.CShexane fraction (CS-HexFr; 10 mg/kg) attenuated cisplatin-induced emesis ∼ 65.85% (P< 0.05); the reference anti-emetic drug, metoclopramide (MCP; 30 mg/kg), produced ∼43.90% reduction (P< 0.05). At acute time point (3rdh), CS-HexFr decreased (P< 0.001) the concentration of 5HT and 5HIAA in the area postrema, brain stem and intestine, while at 18thh (delayed time point) CS-HexFr attenuated (P< 0.001) the upsurge of 5HT caused by cisplatin in the brain stem and intestine and dopamine in the area postrema.CS-HexFr treatment alone did not alter the basal neurotransmitters and their metabolites in the brain areas and intestine except 5HIAA and HVA, which were decreased significantly. In conclusion the anti-emetic effect ofCS-HexFr is mediated by anti-serotonergic and anti-dopaminergic components in a blended manner at the two different time points, i.e., 3rdand 18thh in pigeons.
Evaluating heavy metals contamination in soil and vegetables in the region of North India: Levels, transfer and potential human health risk analysis

Gupta N, Yadav KK, Kumar V, Krishnan S, Kumar S, Nejad ZD, et al.

Environ Toxicol Pharmacol, 2021 Feb;82:103563.
PMID: 33310081 DOI: 10.1016/j.etap.2020.103563

This study determined the heavy metals (HMs) accumulation in different vegetables in different seasons and attributed a serious health hazard to human adults due to the consumption of such vegetables in Jhansi. The total amounts of zinc (Zn), lead (Pb), nickel (Ni), manganese (Mn), copper (Cu), cobalt (Co), and cadmium (Cd) were analysed in 28 composite samples of soil and vegetables (Fenugreek, spinach, eggplant, and chilli) collected from seven agricultural fields. The transfer factor (TF) of HMs from soil to analysed vegetables was calculated, and significant non-carcinogenic health risks due to exposure to analysed heavy metals via consumption of these vegetables were computed. The statistical analysis involving Principal Component Analysis (PCA) and Pearson's correlation matrix suggested that anthropogenic activities were a major source of HMs in the study areas. The target hazard quotient of Cd, Mn, and Pb for fenugreek (2.156, 2.143, and 2.228, respectively) and spinach (3.697, 3.509, 5.539, respectively) exceeded the unity, indicating the high possibilities of non-carcinogenic health risks if regularly consumed by human beings. This study strongly suggests the continuous monitoring of soil, irrigation water, and vegetables to prohibit excessive accumulation in the food chain.
State-of-the-art biosynthesis of tin oxide nanoparticles by chemical precipitation method towards photocatalytic application

Nipa ST, Akter R, Raihan A, Rasul SB, Som U, Ahmed S, et al.

Environ Sci Pollut Res Int, 2022 Feb;29(8):10871-10893.
PMID: 34997495 DOI: 10.1007/s11356-021-17933-1

Tin oxide (SnO2) with versatile properties is of substantial standing for practical application, and improved features of the material are demonstrated in the current issue through the integration of nanotechnology with bio-resources leading to what is termed as biosynthesis of SnO2 nanoparticles (NPs). This review reveals the recent advances in biosynthesis of SnO2 NPs by chemical precipitation method focused on distinct methodologies, characterization, and reaction mechanism along with a photocatalytic application for dye degradation. According to available literature reviews, numerous bio-based precursors selectively extracted from biological substrates have effectively been applied as capping or reducing agents to achieve the metal oxide NPs. The major precursor obtained from the aqueous extract of root barks of Catunaregam spinosa is found to be 7-hydroxy-6-methoxy-2H-chromen-2-one that has been proposed as a model compound for the reduction of metal ions into nanoparticles due to having highly active functional groups, being abundant in plants (67.475 wt%), easy to extract, and eco benign. In addition, the photocatalytic activity of SnO2 NPs for the degradation of organic dyes, pharmaceuticals, and agricultural contaminants has been discussed in the context of a promising bio-reduction mechanism of the synthesis. The final properties are supposed to depend exclusively upon a number of factors, e.g., particle size (
Transformation of hazardous sacred incense sticks ash waste into less toxic product by sequential approach prior to their disposal into the water bodies

Yadav VK, Yadav KK, Alam J, Cabral-Pinto MM, Gnanamoorthy G, Alhoshan M, et al.

Environ Sci Pollut Res Int, 2023 Jun;30(28):71766-71778.
PMID: 34523099 DOI: 10.1007/s11356-021-15009-8

Incense sticks ash is one of the most unexplored by-products generated at religious places and houses obtained after the combustion of incense sticks. Every year, tonnes of incense sticks ash is produced at religious places in India which are disposed of into the rivers and water bodies. The presence of heavy metals and high content of alkali metals challenges a potential threat to the living organism after the disposal in the river. The leaching of heavy metals and alkali metals may lead to water pollution. Besides this, incense sticks also have a high amount of calcium, silica, alumina, and ferrous along with traces of rutile and other oxides either in crystalline or amorphous phases. The incense sticks ash, heavy metals, and alkali metals can be extracted by water, mineral acids, and alkali. Ferrous can be extracted by magnetic separation, while calcium by HCl, alumina by sulfuric acid treatment, and silica by strong hydroxides like NaOH. The recovery of such elements by using acids and bases will eliminate their toxic heavy metals at the same time recovering major value-added minerals from it. Here, in the present research work, the effect on the elemental composition, morphology, crystallinity, and size of incense sticks ash particles was observed by extracting ferrous, followed by extraction of calcium by HCl and alumina by H2SO4 at 90-95 °C for 90 min. The final residue was treated with 4 M NaOH, in order to extract leachable silica at 90 °C for 90 min along with continuous stirring. The transformation of various minerals phases and microstructures of incense sticks ash (ISA) and other residues during ferrous, extraction, calcium, and alumina and silica extraction was studied using Fourier transform infrared (FTIR), dynamic light scattering (DLS), X-ray fluorescence (XRF), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and inductively coupled plasma-optical emission spectroscopy (ICP-OES). DLS was used for analyzing the size during the experiments while FTIR helped in the confirmation of the formation of new products during the treatments. From the various instrumental analyses, it was found that the toxic metals present in the initial incense sticks ash got eliminated. Besides this, the major alkali metals, i.e., Ca and Mg, got reduced during these successive treatments. Initially, there were mainly irregular shaped, micron-sized particles that were dominant in the incense sticks ash particles. Besides this, there were plenty of carbon particles left unburned during combustion. In the final residue, nanosized flowers shaped along with cuboidal micron-sized particles were dominant. present in If, such sequential techniques will be applied by the industries based on recycling of incense sticks ash, then not only the solid waste pollution will be reduced but also numerous value-added minerals like ferrous, silica, alumina calcium oxides and carbonates can be recovered from such waste. The value-added minerals could act as an economical and sustainable source of adsorbent for wastewater treatment in future.
Correction to: Transformation of hazardous sacred incense sticks ash waste into less toxic product by sequential approach prior to their disposal into the water bodies

Yadav VK, Yadav KK, Alam J, Cabral-Pinto MM, Gnanamoorthy G, Alhoshan M, et al.

Environ Sci Pollut Res Int, 2023 Jun;30(28):71779.
PMID: 34739673 DOI: 10.1007/s11356-021-17310-y