Enhanced microwave absorption properties of conducting polymer@graphene composite to counteract electromagnetic radiation pollution: green EMI shielding.

Conducting polymers have been thoroughly investigated and found to have extensive applications in the fields of microwave absorption and electromagnetic (EM) shielding owing to their distinctive characteristics and adaptability. In the present work, conducting polymer (PEDOT and polyaniline) and graphene composites were prepared via an in situ chemical polymerization technique. Further, these composite materials were characterized to determine their potential to address the issue of EM radiation pollution in the microwave frequency (12.4 GHz to 18 GHz). The PEDOT/graphene composites exhibited significant shielding effectiveness of up to 46.53 dB, achieving a green index (gs) of 1.17. Also, absorption was observed to be the dominant shielding mechanism in all the samples owing to significant dielectric losses (ε''/ε' ≈ 1.9-3.1) and microwave conductivity (σs = 19.9-73.6 S m-1) in the samples at 18 GHz. Both dielectric loss and conduction loss occurred because of the strong interactions involving polarization, charge propagation, and the creation of conductive routes through the incorporation of graphene in the polymer matrix. These properties/shielding results indicate the potential of the composites to be used as lightweight EM shielding materials. These materials are suitable shield materials for electronic devices to protect them from harmful electromagnetic radiation, making them vital in various applications.

Artificial intelligence revolutionizing drug development: Exploring opportunities and challenges.

By harnessing artificial intelligence (AI) algorithms and machine learning techniques, the entire drug discovery process stands to undergo a profound transformation, offering a myriad of advantages. Foremost among these is the ability of AI to conduct swift and efficient screenings of expansive compound libraries, significantly augmenting the identification of potential drug candidates. Moreover, AI algorithms can prove instrumental in predicting the efficacy and safety profiles of candidate compounds, thus endowing invaluable insights and reducing reliance on extensive preclinical and clinical testing. This predictive capacity of AI has the potential to streamline the drug development pipeline and enhance the success rate of clinical trials, ultimately resulting in the emergence of more efficacious and safer therapeutic agents. However, the deployment of AI in drug discovery introduces certain challenges that warrant attention. A primary hurdle entails the imperative acquisition of high-quality and diverse data. Furthermore, ensuring the interpretability of AI models assumes critical importance in securing regulatory endorsement and cultivating trust within scientific and medical communities. Addressing ethical considerations, including data privacy and mitigating bias, represents an additional momentous challenge, requiring assiduous navigation. In this review, we provide an intricate and comprehensive overview of the multifaceted challenges intrinsic to conventional drug development paradigms, while simultaneously interrogating the efficacy of AI in effectively surmounting these formidable obstacles.

Effect of Curcumin and Coenzyme Q10 Alone and in Combination on Learning and Memory in an Animal Model of Alzheimer's Disease.

The most frequent neurodegenerative illness among senior people and the main cause of dementia is Alzheimer's disease. The present dementia medications available only help with the symptoms of cognitive deficits and have several negative effects. The current study's goal is to assess the effects of curcumin and coenzyme Q10, two herbal medicines, both separately and in combination, on learning and memory before comparing them to the industry standard drug. A total of 42 adult healthy Wistar rats were used in our study. In this experiment, rats were given daily doses of 2.5 mg/kg of body weight of scopolamine hydrobromide for 7 days to induce Alzheimer's disease. On the eighth day, behavioural testing was conducted. Following testing, scopolamine and the test medications were given daily for the following 21 days. On days 29 and 30, behavioural testing was conducted once more, and then animals were slaughtered. Brain homogenate was produced for the estimation of molecular and biochemical markers. Curcumin has demonstrated a dose-response relationship, with a higher dose (200 mg/kg b.w. p.o.) being more effective than a lower dose (100 mg/kg b.w. p.o.). Similar to the greater dose of curcumin, coenzyme Q10 (200 mg/kg b.w. p.o.) has also been found to improve memory and learning. Higher doses of curcumin and coenzyme Q10 had more pronounced and meaningful effects. Acetylcholinesterase and TNF levels increased in scopolamine-induced memory impairment, but these effects were restored by the test medications, and improved by the combined therapy. These outcomes are comparable to those of the common medication memantine. As a result, we may infer from our results that curcumin at higher doses and its combination with coenzyme Q10 (200 mg/kg b.w. p.o.) have a significant impact on cognitive impairment in animal models of Alzheimer's disease and can be utilised alone or as an add-on therapy for the condition.

Yoga Meets Intelligent Internet of Things: Recent Challenges and Future Directions.

The physical and mental health of people can be enhanced through yoga, an excellent form of exercise. As part of the breathing procedure, yoga involves stretching the body organs. The guidance and monitoring of yoga are crucial to ripe the full benefits of it, as wrong postures possess multiple antagonistic effects, including physical hazards and stroke. The detection and monitoring of the yoga postures are possible with the Intelligent Internet of Things (IIoT), which is the integration of intelligent approaches (machine learning) and the Internet of Things (IoT). Considering the increment in yoga practitioners in recent years, the integration of IIoT and yoga has led to the successful implementation of IIoT-based yoga training systems. This paper provides a comprehensive survey on integrating yoga with IIoT. The paper also discusses the multiple types of yoga and the procedure for the detection of yoga using IIoT. Additionally, this paper highlights various applications of yoga, safety measures, various challenges, and future directions. This survey provides the latest developments and findings on yoga and its integration with IIoT.

Anti-oxidative and anti-neuroinflammatory role of Necrostatin-1s and docosahexaenoic acid in RIP-1-mediated neurotoxicity in MPTP-induced Parkinson's disease model.

Parkinson's disease (PD) is a neuromuscular ailment that affects people in their later years and causes both motor and non-motor deficits. Receptor-interacting protein-1 (RIP-1) is a critical participant in necroptotic cell death, possibly through an oxidant-antioxidant imbalance and cytokine cascade activation in PD pathogenesis. The present study examined the role of RIP-1-mediated necroptosis and neuroinflammation in the MPTP-induced PD mouse model, as well as their protection by Necrostatin-1s (an RIP signalling inhibitor), antioxidant DHA and their functional interaction. BALB/c mice were given acute MPTP therapy (4 injections of 15 mg/kg i.p. at 2-h intervals) on day 1. After MPTP intoxication, Necrostatin-1s (Nec-1s; 8 mg/kg/day, i.p.) and DHA (300 mg/kg/day, p.o.) treatments were given once daily for 7 days. The Nec-1s treatment prevented MPTP-induced behavioural, biochemical and neurochemical alterations, and the addition of DHA increases Nec-1s' neuroprotective impact. In addition, Nec-1s and DHA significantly improve the survival of TH-positive dopaminergic neurons and lower expression levels of the inflammatory cytokines, IL-1ß and TNF-α. Furthermore, Nec-1s dramatically reduced RIP-1 expression, whereas DHA had little effect. Our research raises the possibility that neuroinflammatory signalling and acute MPTP-induced necroptosis are both mediated by TNFR1-driven RIP-1 activity. In this study, RIP-1 ablation through Nec-1s and the addition of DHA showed a reduction in the levels of pro-inflammatory and oxidative markers, as well as protection from MPTP-driven dopaminergic degeneration and neurobehavioural changes, suggesting potential therapeutic applications. For a better understanding, additional research about the mechanism(s) behind Nec-1s and DHA is required.

Neuroprotective role of chloroquine via modulation of autophagy and neuroinflammation in MPTP-induced Parkinson's disease.

Parkinson's disease (PD) is a neuro-motor ailment that strikes adults in their older life and results in both motor and non-motor impairments. In neuronal and glial cells, PD has recently been linked to a dysregulated autophagic system and cerebral inflammation. Chloroquine (CQ), an anti-malarial drug, has been demonstrated to suppress autophagy in a variety of diseases, including cerebral ischemia, Alzheimer's disease (AD), and Traumatic brain injury (TBI), while its involvement in PD is still unclear. BALB/c mice were randomly allocated to one of four groups: 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), CQ treatment with or without MPTP, or control. The CQ treatment group received CQ (intraperitoneally, 8 mg/kg body weight) after 1 h of MPTP induction on day 1, and it lasted for 7 days. CQ therapy preserves dopamine levels stable, inhibits tyrosine hydroxylase (TH) positive dopaminergic cell death, and lowers oxidative stress. CQ reduces the behavioural, motor, and cognitive deficits caused by MPTP after injury. Furthermore, CQ therapy slowed aberrant neuronal autophagy (microtubule-associated protein-1 light chain 3B; LC3B & Beclin1) and lowered expression levels of the inflammatory cytokines interleukin 1 (IL-1ß) and tumour necrosis factor (TNF-α) in the mice brain. In addition, CQ's antioxidant and anti-inflammatory effects were also tested in MPTP-mediated cell death in PC12 cells, demonstrating that CQ has a neurorestorative impact by successfully rescuing MPTP-induced ROS generation and cell loss. Our findings show that CQ's can help to prevent dopaminergic degeneration and improve neurological function after MPTP intoxication by lowering the harmful effects of neuronal autophagy and cerebral inflammation.

A Novel Smart Belt for Anxiety Detection, Classification, and Reduction Using IIoMT on Students' Cardiac Signal and MSY.

The prevalence of anxiety among university students is increasing, resulting in the negative impact on their academic and social (behavioral and emotional) development. In order for students to have competitive academic performance, the cognitive function should be strengthened by detecting and handling anxiety. Over a period of 6 weeks, this study examined how to detect anxiety and how Mano Shakti Yoga (MSY) helps reduce anxiety. Relying on cardiac signals, this study follows an integrated detection-estimation-reduction framework for anxiety using the Intelligent Internet of Medical Things (IIoMT) and MSY. IIoMT is the integration of Internet of Medical Things (wearable smart belt) and machine learning algorithms (Decision Tree (DT), Random Forest (RF), and AdaBoost (AB)). Sixty-six eligible students were selected as experiencing anxiety detected based on the results of self-rating anxiety scale (SAS) questionnaire and a smart belt. Then, the students were divided randomly into two groups: experimental and control. The experimental group followed an MSY intervention for one hour twice a week, while the control group followed their own daily routine. Machine learning algorithms are used to analyze the data obtained from the smart belt. MSY is an alternative improvement for the immune system that helps reduce anxiety. All the results illustrate that the experimental group reduced anxiety with a significant (p < 0.05) difference in group × time interaction compared to the control group. The intelligent techniques achieved maximum accuracy of 80% on using RF algorithm. Thus, students can practice MSY and concentrate on their objectives by improving their intelligence, attention, and memory.

Effects of mangiferin and its combination with nNOS inhibitor 7-nitro-indazole (7-NI) in 6-hydroxydopamine (6-OHDA) lesioned Parkinson's disease rats.

Nitric oxide (NO), generated by nitric oxide synthase enzymes (NOS), has an important role in maintaining synapse plasticity, neuro-modulation, and other physiological functions in the brain. NO thus generated also has a key role in formation of reactive oxygen and reactive nitrite species and subsequent neuronal damage due to sustained oxidative stress. Due to its property of ROS and RNOS generation, NO plays a significant role in Parkinson's disease (PD) pathogenesis. Therefore, we evaluated the effect of mangiferin alone and in combination with nNOS inhibitor 7-nitro-indazole (7-NI) in 6-OHDA lesioned rats. Male Wistar rats weighing 200-250 g (n = 8/group) were used in the study. Stereotactic surgeries of rats were done to induce 6-OHDA lesioning in rats. Then, treatment with mangiferin alone and in combination with 7-NI 10 mg/kg was done from days 14 to 42 for 28 days. On day 42, rats were subjected to behavioral studies, and their brains were taken out after euthanasia to perform biochemical and molecular studies. Treatment with mangiferin and 7-NI significantly increases locomotor parameters in 6-OHDA lesioned rats. Treatment with mangiferin 45 µg and 7-NI 10 mg/kg alone and in combination significantly reduces oxidative stress along with decrease in concentration of pro-inflammatory cytokines, cyclooxygenase 2, total nitrite (NOx) and FOS B concentration. Results of this study suggest that treatment with 7-NI 10 mg/kg further enhances anti-inflammatory and anti-parkinsonism activity of mangiferin owing to its property of inhibiting nNOS mediated FOS B signaling and thereby inhibiting mRNA formation of TNF-α and IL-6.

A prospective observational study to evaluate Glutathione S-transferase gene polymorphism and its association with Antitubercular drugs induced liver injury in tertiary hospital.

BACKGROUND: Anti-TB drugs are most common cause of idiosyncratic hepatotoxicity worldwide. Reactive metabolite formed during drug metabolism has been involved in a clinical toxicity are described as 'idiosyncratic' drug induce liver injury (DILI). We have observed the distribution of glutathione S -transferase (GST) gene polymorphism & its association with drug-induced liver injury in patients taking anti-tubercular treatment. METHODS: A prospective observational study including 96 patients receiving anti-tubercular treatment. Blood sample was collected for LFT and gene extraction after ruling out other cause of liver injury. DNA extraction for GST gene was done follow by polymerase chain reaction to identify homozygous null mutation at GSTM1 and GSTT1 loci. Association of GSTM1 and GSTT1 gene with DILI was seen. RESULTS: Out of 96 tubercular patients under treatment, drug induced liver injury was found in 21 (21.9%) patients and 75 does not develop DILI, GST M1 gene null mutation was observed in 14 (66.7%), GST T1 gene null mutation was observed in 9 (42.9%), Both GST gene null mutation was observed in 8 (38.1%) in DILI group. CONCLUSION: The GSTM1 gene null mutation and both GSTM1 and T1 gene null mutation were a risk factor for the development of DILI. But there is no significant association between GSTT1 gene null mutation and DILI in TB patients.

Pharmacological, Biochemical and Immunological Studies on Protective Effect of Mangiferin in 6-Hydroxydopamine (6-OHDA)-Induced Parkinson's Disease in Rats.

Background: Parkinson's disease is a neurodegenerative disorder and is marked by inflammation and death of neurons in the striatum region of the midbrain. It has been reported that expression of NF-κB increases during Parkinson's disease, which promotes oxidative stress, stimulates release of proinflammatory cytokines, and induces expression of nitric oxide. Therefore, in this study, we have used mangiferin a specific NF-κB inhibitor. Mangiferin is a polyphenolic compound traditionally used for its antioxidant and anti-inflammatory properties. Methods: The study utilized male Wistar rats weighing 200-250 g (56 rats; n = 8/group). On day "0," stereotaxic surgery of rats was done to induce 6-hydroxydopamine lesioning in rats. Coordinates for substantia nigra were anteroposterior-2 mm, mediolateral-5 mm and dorsoventral-8.2 mm. After 14 days, those rats which show at least 210 contralateral rotations after administration of apomorphine (0.5 mg/kg S.C.) were selected for the study and were given treatment for 28 days. On day 28 of treatment, rats were subjected to behavioral studies to evaluate the effect of mangiferin and their brains were taken out after euthanasia to perform biochemical, molecular and immunological studies. Results: Treatment with mangiferin significantly improves the key parameters of locomotor activity and oxidative stress and reduces the parameters of inflammatory stress. Also, the activity of caspases was reduced. Significant decrease in activity of both cyclooxygenase 1 and 2 was also observed. Maximum improvement in all parameters was observed in rats treated with grouping of mangiferin 45 µg/kg and levodopa 10 mg/kg. Treatment with levodopa alone has no significant effect on biochemical and molecular parameters though it significantly improves behavioral parameters. Conclusion: Current treatment of Parkinson's disease does not target progression of Parkinson's disease. Results of this study suggest that mangiferin has protective effect in hemi-Parkinsonian rats. Therefore, the combination therapy of mangiferin and levodopa can be helpful in management of Parkinson's disease.

Effect of Boswellia Serrata Extract on Acute Inflammatory Parameters and Tumor Necrosis Factor-α in Complete Freund's Adjuvant-Induced Animal Model of Rheumatoid Arthritis.

CONTEXT: The worldwide prevalence of rheumatoid arthritis (RA) is about 1%, whereas in India, it is approximately 0.75%. The current therapy for RA includes nonsteroidal anti-inflammatory drugs corticosteroids, disease-modifying anti-rheumatic drugs and some recently developed biologic agents, but all of these are associated with adverse effects. Some herbal drugs, such as Boswellia serrata, have been reported to possess anti-inflammatory activity. AIMS: The aim of this study is to evaluate the anti-arthritic activity of Boswellia serrata extract (BSE) in complete Freund's adjuvant (CFA)-induced arthritis in rats. MATERIALS AND METHODS: Thirty-six Wistar rats were divided into six equal groups. RA was induced by intradermal injection of 0.1 ml CFA in hind paw. Body weight, ankle diameter, paw volume, arthritic index, tumor necrosis factor-α (TNF-α), and histopathological examination were assessed. The experimental data were statistically assessed by one-way analysis of variance (ANOVA). STATISTICAL ANALYSIS USED: The recorded data were analyzed using paired t-test and ANOVA test using SPSS. The data were analyzed and represented as mean difference. Value of P < 0.05 was considered statistically significant. RESULTS: BSE at dose 180 mg/kg showed statistically significant improvement in body weight and decrease in ankle diameter and arthritic index (P < 0.05); however, there was insignificant change in paw volume (P = 0.056). This improvement was comparable with Indomethacin. The level of TNF-α did not show any statistically significant change (P = 0.076). Histopathological results also exhibited a reduction in inflammatory parameters. CONCLUSIONS: BSE might have usefulness as an adjunct to conventional therapy of RA.

Pharmacological and biochemical studies on protective effects of mangiferin and its interaction with nitric oxide (NO) modulators in adjuvant-induced changes in arthritic parameters, inflammatory, and oxidative biomarkers in rats.

Current study was designed to evaluate protective effect of mangiferin and its interaction with low dose of nitric oxide (NO) modulators in complete Freund's adjuvant (CFA) inoculated rats. Male wistar rats (200-300 g, n = 8 per group) were used in the study. On day ''0'' of study arthritis was induced in rats by injecting 0.2 ml CFA in sub-planter region of right hind paw of animals. Treatment with methotrexate (5 mg/kg), mangiferin (10-30 mg/kg) alone and in combination with NO modulators was given (i.p.) from days 14 to 28. After 28 days, blood and joint synovial fluid was collected for biochemical analysis and rat paws were excised to estimate MDA and SOD in tissue (paw) homogenates. CFA inoculation significantly increases (1) arthritic index, (2) ankle diameter, (3) paw volume, and (4) serum TNF-α, IL-6, IL-1ß, and synovial TNF-α levels (p < 0.001). The serum Th1 (IFN-γ) and Th2 (IL-4) cytokine levels, MDA levels in rat paw tissue homogenates and serum NF-κB levels were also found significantly increased. Significant decrease in serum IL-10 levels and SOD activity was found after CFA inoculation. These CFA-induced arthritic changes, cytokine profile, and oxidative stress markers were significantly reversed by mangiferin (10-30 mg/kg) treatment alone and in combination with L-arginine and L-NAME nitric oxide modulators (p < 0.05). Treatment with methotrexate (5 mg/kg) also significantly reversed these adjuvant changes (p < 0.05). However, effect of methotrexate was less marked as compared to mangiferin (30 mg/kg) alone and in combination with L-NAME (10 mg/kg), but was comparable or slightly better than mangiferin (10 and 20 mg/kg). Thus, on the basis of our findings, we can suggest that interaction of mangiferin with nitric oxide modulators may have therapeutic value for chronic inflammatory disease such as RA.

The potential role of neuroinflammation and transcription factors in Parkinson disease.

Parkinson disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons affected by inflammatory processes. Post-mortem analyses of brain and cerebrospinal fluid from PD patients show the accumulation of proinflammatory cytokines, confirming an ongoing neuroinflammation in the affected brain regions. These inflammatory mediators may activate transcription factors-notably nuclear factor κB, Ying-Yang 1 (YY1), fibroblast growth factor 20 (FGF20), and mammalian target of rapamycin (mTOR)-which then regulate downstream signaling pathways that in turn promote death of dopaminergic neurons through death domain-containing receptors. Dopaminergic neurons are vulnerable to oxidative stress and inflammatory attack. An increased level of inducible nitric oxide synthase observed in the substantia nigra and striatum of PD patients suggests that both cytokine-and chemokine-induced toxicity and inflammation lead to oxidative stress that contributes to degeneration of dopaminergic neurons and to disease progression. Lipopolysaccharide activation of microglia in the proximity of dopaminergic neurons in the substantia nigra causes their degeneration, and this appears to be a selective vulnerability of dopaminergic neurons to inflammation. In this review, we will look at the role of various transcription factors and signaling pathways in the development of PD.

La Enfermedad de Parkinson (EP) es un trastorno neurodegenerativo caracterizado por procesos inflamatorios en neuronas dopaminérgicas. El análisis post-mortem de cerebro y líquido céfalo raquídeo de pacientes con EP muestra la acumulación de citoquinas proinflamatorias, lo que confirma un proceso neuroinflamatorio en las regiones cerebrales afectadas. Estos mediadores inflamatorios pueden activar factores de transmisión­en especial el factor nuclear κB, el Ying-Yang 1 (YY1), el factor de crecimiento de fibroblastos 20 (FGF20) y un blanco de rapamicina en los mamíferos (mTOR)­los que regulan las vías de señales descendentes y a la vez promueven la muerte de neuronas dopaminérgicas, a través de receptores que tienen un dominio de muerte. Las neuronas dopaminérgicas son vulnerables al estrés oxidativo y al ataque inflamatorio. En la sustancia nigra y el estriado de pacientes con EP se ha observado un aumento del nivel de sintetasa de óxido nítrico inducible, lo que sugiere que tanto la inflamación como la toxicidad inducidas por citoquinas y quimioquinas llevan al estrés oxidativo, lo que contribuye a la degeneración de las neuronas dopaminérgicas y al avance de la enfermedad. La activación de lipopolisacáridos de la microglía, en la proximidad de las neuronas dopaminérgicas en la sustancia nigra, provoca su degeneración y esto parece ser una vulnerabilidad selectiva de las neuronas dopaminérgicas a la inflamación. En este artículo se revisa el papel de varios factores de transcripción y vías de señales en el desarrollo de la EP.

La maladie de Parkinson (MP) est un trouble dégéneratif caractérisé par l'atteinte des neurones dopaminergiques par des processus inflammatoires. Des analyses post-mortem du cerveau et du liquide céphalo-rachidien de patients parkinsoniens montrent l'accumulation de cytokines pro-inflammatoires, confirmant la présence d'une neuro-inflammation dans les régions cérébrales affectées. Ces médiateurs inflammatoires activent des facteurs de transcription, en particulier le facteur nucléaire κB, le Ying-Yang 1 (YY1), le facteur 20 de croissance du fibroblaste (FGF20) et mTOR (cible de la rapamytine chez les mammifères), qui régulent ensuite les voies de signalisation en aval, qui à leur tour favorisent la mort des neurones dopaminergiques à travers des récepteurs à domaine de mort. Les neurones dopaminergiques sont vulnérables au stress oxydatif et à l'attaque inflammatoire. Une augmentation des taux de l'oxyde nitrique synthase inductible observée dans la substance grise et le striatum des patients MP suggère que l'inflammation et la toxicité induites par les chémokines et les cytokines conduisent à un stress oxydatif qui contribue à la dégénérescence des neurones dopaminergiques et à la progression de la maladie. L'activation des lipopolysaccharides de la microglie proche des neurones dopaminergiques dans le locus niger provoque leur dégénérescence, ce qui semble être dû à une vulnérabilité sélective des neurones dopaminergiques à l'inflammation. Dans cet article, nous analysons le rôle de divers facteurs de transcription et voies de signalisation dans l'apparition de la MP.

Role of neuroinflammation and latent transcription factors in pathogenesis of Parkinson's disease.

Parkinson's disease (PD) the second most common age-associated progressive neurodegenerative disorder is characterized by loss of dopaminergic neurons, cytoplasmic inclusions of aggregated proteins (Lewy bodies), and neuroinflammation. The inflammation of neurons causes release of various inflammatory mediators (IFNs, EGF, IL5, IL6, HGF, LIF and BMP2). The hallmarks of neuroinflammation are the presence of activated microglia and reactive astrocytes in the parenchyma of the CNS and increased production of cytokines, chemokines, prostaglandins, complement cascade proteins, and reactive oxygen and nitrogen species (ROS/RNS) which in some cases can result in disruption of the blood brain barrier and direct participation of the adaptive immune system. Latent transcription factors such as NF-κB, STAT 3, AP1, and SMAD 7, Toll like receptors and FAF 1 are constitutively upregulated in activated microglia. Toll-like receptors when activated promote NF-κB signaling thus promoting a vicious cycle of neuroinflammation. These transcription factors take dopaminergic neurons to apoptotic pathway via p53 and other death domain receptors. Neuroprotective signaling pathways such as mTOR, SOCS, and TGF-ß down regulated during development of PD. YY1 signaling, which has protective effect against α-Synuclein toxicity, is significantly decreased in PD patients. In summary we can say that transcription factors promoting inflammation such as NF-κB, STAT 3, AP 1, and Toll-like receptors are constitutively upregulated in PD, while neuroprotective pathways such as mTOR, TGF-ß, and YY1 are substantially downregulated in microglia of PD patients.

Pharmacological studies on the anti-inflammatory and immunomodulatory role of pentoxifylline and its interaction with nitric oxide (NO) in experimental arthritis in rats.

AIM: Present study was designed to evaluate protective effects of pentoxifylline and its potentiation with low dose of nitric oxide (NO) modulators in adjuvant-induced experimental arthritis in rats. METHOD: Wistar rats (200-300 g, n = 8 per group) of both sexes were used in the study. On day "0" experimental arthritis was induced by injecting 0.2 ml of Complete Freund's adjuvant (CFA) in sub-planter region of right hind paw of animals. Pentoxifylline treatment alone and in combination with NO modulators was given (i.p.) from day 14 to 28. Various arthritic parameters were recorded and blood and joint synovial fluid was collected for biochemical analysis. RESULTS: CFA inoculation significantly increases (1) arthritic index (2) ankle diameter (3) paw volume (4) histopathology score (5) serum TNF-α, IL-6, IL-1ß and synovial TNF-α levels (p < 0.001) (6) serum Th1 and Th2 cytokine levels g) MDA levels in rat paw tissue homogenates (7) serum NF-κB levels. Significant decrease in serum IL-10 levels and SOD activity was observed in rats after CFA inoculation. Decrease in body weight and suppressed general quality of life of CFA inoculated rats was also observed. These CFA-induced arthritic changes were significantly reversed by pentoxifylline alone and in combination with low dose of NO modulators (p < 0.05). CONCLUSION: These results are suggestive of protective effects of pentoxifylline and its potentiation in combination with low dose of NO modulators. These results may provide new pharmacological therapy for management of rheumatoid arthritis (RA).

Pharmacological and biochemical studies on the protective effects of melatonin during stress-induced behavioral and immunological changes in relation to oxidative stress in rats.

Stress is known to precipitate neuropsychiatric diseases, and depending upon its nature and intensity it can also influence the functioning of the immune system. Melatonin (N-acetyl-5-methoxy tryptamine) a pineal gland hormone and potent antioxidant is known to protect against many diseases. Effect of melatonin in stress-induced neuro-immunomodulation is not well elucidated. Therefore in the present study, the protective effects of melatonin were evaluated in restraint stress (RS)-induced behavioral and immunological changes in rats. RS for 1 h significantly reduces (i) percentage of open-arm entries and (ii) percentage of time spent on open-arm in elevated plus maze (EPM) test parameters (p < 0.01) and significant increase in MDA levels in brain homogenate when compared to non-RS control groups (p < 0.05). In immunological studies, both humoral and cell-mediated immune responses to antigen were significantly suppressed by RS for 1 h for 5 consecutive days, as evidenced by significant reduction in (i) anti-SRBC antibody titre, (ii) PFC counts, (iii) percentage change in paw volume, and (iv) Th1 (IFN-γ) and Th2 (IL-4) cytokine levels (p < 0.001 in all parameters). These RS-induced immunological changes were associated with significantly increased lipid peroxidation (MDA) levels in serum and significantly decreased activity of (i) SOD, (ii) CAT, and (iii) GSH levels in RS (X5)-exposed group (p < 0.02). Pretreatment with melatonin (10, 50, and 100 mg/kg) significantly reversed these RS-induced changes in EPM test parameters and humoral and cell-mediated immunological parameters, as well as oxidative stress markers in a dose-dependent manner by differential degrees (p < 0.001). Results are strongly suggestive of the involvement of free radicals during stress-induced neurobehavioral and immunological changes. These changes were significantly restored by melatonin pretreatment. We can conclude that melatonin may have a protective role during such stress-induced neuro-immunomodulation.

Protective role of theophylline and their interaction with nitric oxide (NO) in adjuvant-induced rheumatoid arthritis in rats.

Theophylline (non-specific PDE inhibitor) and their interactions with nitric oxide modulators were evaluated in adjuvant-induced arthritic model of rats. Wistar rats (200-300g), 8 animals per group were used in the study. The animals were injected with 0.1mL of squalene and 0.2mL of complete Freund's adjuvant on day (0) in sub-planter region of right hind paw controls received only saline. The treatment with theophylline and nitric oxide modulators were done from day 14 to day 28. Arthritis indexes, ankle diameter, paw volume, and body weight were determined to assess RA progression from day (0) to day 28. On day 28 animals were sacrificed and their blood collected for IL-10 and TNF-α cytokine levels and hind paw for pathological analysis. Synovial fluid from joint spaces of CFA inoculated rats was collected to estimate TNF-α level in synovial fluid. The data obtained was analyzed by two-way ANOVA followed by the Newman-Keuls post-hoc test. Theophylline (10 and 20mg/kg) significantly decreased adjuvant induced increased arthritis-index, paw volume and ankle diameter (p<0.05 in all parameters) compared to only adjuvant control group. It also reversed adjuvant induced slight decrease in body weight to normalcy. l-Arginine 100mg/kg+theophylline 20mg/kg suppressed TNF-α and elevates IL-10 level as well as reversed adjuvant-induced elevated arthritic parameters as compared to only adjuvant and prednisone group (p<0.001). Synovial TNF-α level of adjuvant only group was several fold higher than its serum level. Treatment with theophylline 20mg/kg significantly reduces synovial TNF-α level as compared to adjuvant only group. Theophylline 20mg/kg+L-NAME 10mg/kg significantly reversed these adjuvant-induced changes in immunological, histopathological and arthritis parameters (p<0.05).

Antihyperglycemic and antihyperlipidemic effects of Salvadora persica in streptozotocin-induced diabetic rats.

CONTEXT: Many synthetic antidiabetic components show toxic and/or mutagenic effects. Hence, attention has been given to naturally occurring antidiabetic components. Identification of effective antidiabetic components from plants origin is an ideal strategy for new drug development. The fresh root, bark, and leaves of Salvadora persica L. (Salvadoraceae) have been used in folk medicine for the treatment of a wide range of medical problems such as cough, asthma, scurvy, piles, rheumatism, leprosy, and gonorrhea disorders. OBJECTIVE: The S. persica root extract was investigated for the reduction of the risk of diabetes in diabetic rats. MATERIAL AND METHODS: The hydro-alcoholic root extract, 200 and 400 mg/kg, was fed to streptozotocin-induced diabetic rats for 21 d. Blood serum glucose, lipid profile, body weight, and food intake were monitored at 0, 7, 14, and 21 d after induction of diabetes. RESULTS: S. persica hydro-alcoholic root extract was not toxic at doses up to 1200 mg/kg. Significant reduction of blood glucose and lipid profile in diabetic rats treated with 400 mg/kg hydro-alcoholic root extract after 21 d versus diabetic control and glibenclamide-treated rats. The glibenclamide and root extract-treated group's peak values of blood glucose significantly decreased from 281.50 to 106 mg/dL and 285.50 to 150.25 mg/dL, respectively. Hence, in this study, observations showed that root hydro-alcoholic reduced the blood glucose level in diabetic rats but values did not return to normal controls. CONCLUSION: The research suggests that the root extract was significantly effective when compared with control and standard in the treatment of hyperlipidemia and hyperglycemia in diabetic rats. Therefore, it may be beneficial to diabetic patients.

Pharmacological and biochemical studies on the role of free radicals during stress-induced immunomodulation in rats.

The present study was designed to evaluate the role of free radicals in restraint stress (RS)-induced modulation of immune responses in rats. RS significantly suppressed both humoral and cell-mediated immune responses as evidenced by reduced (a) anti-SRBC antibody titre (b) splenic Plaque Forming Cell counts, (c) footpad thickness response, and (d) IFN-γ and IL-4 levels. Assay for oxidative stress markers in blood showed that there was significant enhancement in plasma corticosterone and products of lipid peroxidation, viz. malondialdehyde and lowered reduced glutathione levels on exposure to RS. Further, this was associated with decreased antioxidant enzyme activity, viz. superoxide dismutase and catalase. These RS-induced changes in immunological and oxidative stress markers were markedly attenuated by pretreatment with the antioxidants, L-ascorbic acid (100 and 200 mg/kg) and α-tocopherol (30 and 60 mg/kg), by differential degrees. The combination of L-ascorbic acid and α-tocopherol was shown to have synergistic effects on reversal of these RS-induced effects. The results suggest that reactive oxygen species may be involved in stress-induced immunomodulation.

Protective effects of different antioxidants against endosulfan-induced oxidative stress and immunotoxicity in albino rats.

Endosulfan exposure (8 and 16 mg/kg) to rats significantly decreased the activities of superoxide dismutase and catalase, level of reduced glutathione and increased lipid peroxidation. The primary and secondary antiSRBC antibody titers, plaque forming cells counts and delayed hypersensivity reaction, and the TH1 or TH2 cytokines levels were significantly suppressed in a dose dependent manner. L-ascorbic acid and alpha-tocopherol produced a synergistic reversal of oxidative stress parameters following endosulfan exposure. N-acetylcysteine produced significant reversal of altered oxidative stress parameters and immune response after endosulfan exposure. A significant attenuation of the oxidative stress markers and immunotoxicity with a combined therapy of L-ascorbic acid plus alpha-tocopherol and with N-acetylcysteine was clearly demonstrated by the present results.