Mechanical release of homogenous proteins from supramolecular gels.

A long-standing challenge is how to formulate proteins and vaccines to retain function during storage and transport and to remove the burdens of cold-chain management. Any solution must be practical to use, with the protein being released or applied using clinically relevant triggers. Advanced biologic therapies are distributed cold, using substantial energy, limiting equitable distribution in low-resource countries and placing responsibility on the user for correct storage and handling. Cold-chain management is the best solution at present for protein transport but requires substantial infrastructure and energy. For example, in research laboratories, a single freezer at -80 °C consumes as much energy per day as a small household1. Of biological (protein or cell) therapies and all vaccines, 75% require cold-chain management; the cost of cold-chain management in clinical trials has increased by about 20% since 2015, reflecting this complexity. Bespoke formulations and excipients are now required, with trehalose2, sucrose or polymers3 widely used, which stabilize proteins by replacing surface water molecules and thereby make denaturation thermodynamically less likely; this has enabled both freeze-dried proteins and frozen proteins. For example, the human papilloma virus vaccine requires aluminium salt adjuvants to function, but these render it unstable against freeze-thaw4, leading to a very complex and expensive supply chain. Other ideas involve ensilication5 and chemical modification of proteins6. In short, protein stabilization is a challenge with no universal solution7,8. Here we designed a stiff hydrogel that stabilizes proteins against thermal denaturation even at 50 °C, and that can, unlike present technologies, deliver pure, excipient-free protein by mechanically releasing it from a syringe. Macromolecules can be loaded at up to 10 wt% without affecting the mechanism of release. This unique stabilization and excipient-free release synergy offers a practical, scalable and versatile solution to enable the low-cost, cold-chain-free and equitable delivery of therapies worldwide.

Exploring the Potential of Nitrogen-Doped Graphene in ZnSe-TiO2 Composite Materials for Supercapacitor Electrode.

The current study explores the prospective of a nitrogen-doped graphene (NG) incorporated into ZnSe-TiO2 composites via hydrothermal method for supercapacitor electrodes. Structural, morphological, and electronic characterizations are conducted using XRD, SEM, Raman, and UV analyses. The electrochemical study is performed and galvanostatic charge-discharge (GCD) and cyclic voltammetry (CV) are evaluated for the supercapacitor electrode material. Results demonstrate improved performance in the ZnSe-NG-TiO2 composite, indicating its potential for advanced supercapacitors with enhanced efficiency, stability, and power density. Specific capacity calculations and galvanic charge-discharge experiments confirmed the promising electrochemical activity of ZnSe-NG-TiO2, which has a specific capacity of 222 C/g. The negative link among specific capacity and current density demonstrated the composite's potential for high energy density and high-power density electrochemical devices. Overall, the study shows that composite materials derived from multiple families can synergistically improve electrode characteristics for advanced energy storage applications.

Spatial distribution of physicochemical parameters and drinking and irrigation water quality indices in the Jhelum River, Pakistan.

Sustainable management of river systems is a serious concern, requiring vigilant monitoring of water contamination levels that could potentially threaten the ecological community. This study focused on the evaluation of water quality in the Jhelum River (JR), Azad Jammu and Kashmir, and northern Punjab, Pakistan. To achieve this, 60 water samples were collected from various points within the JR Basin (JRB) and subjected to a comprehensive analysis of their physicochemical parameters. The study findings indicated that the concentrations of physicochemical parameters in the JRB water remained within safety thresholds for both drinking and irrigation water, as established by the World Health Organization and Pakistan Environmental Protection Agency. These physicochemical parameters refer to various chemical and physical characteristics of the water that can have implications for both human health (drinking water) and agricultural practices (irrigation water). The spatial variations throughout the river course distinguished between the upstream, midstream, and downstream sections. Specifically, the downstream section exhibited significantly higher values for physicochemical parameters and a broader range, highlighting a substantial decline in its quality. Significant disparities in mean values and ranges were evident, particularly in the case of nitrates and total dissolved solids, when the downstream section was compared with its upstream and midstream counterparts. These variations indicated a deteriorating downstream water quality profile, which is likely attributable to a combination of geological and anthropogenic influences. Despite the observed deterioration in the downstream water quality, this study underscores that the JRB within the upper Indus Basin remains safe and suitable for domestic and agricultural purposes. The JRB was evaluated for various irrigation water quality indices. The principal component analysis conducted in this study revealed distinct covariance patterns among water quality variables, with the first five components explaining approximately 79% of the total variance. Recommending the continued utilization of the JRB for irrigation, we advocate for the preservation and enhancement of water quality in the downstream regions.

Evaluation of irrigation, drinking, and risk indices for water quality parameters of alpine lakes.

Alpine lakes are aquatic ecosystems that maintain and regulate water supply for the downstream streams, rivers, and other reservoirs. This study examined the water characteristics of various alpine lakes in Gilgit-Baltistan, Northern Pakistan. For this purpose, water was sampled and investigated for basic parameters, anions, and cations using the multi-parameter analyzers and atomic absorption spectrophotometer. Physicochemical parameters of alpine lakes were noted under the World Health Organization water guidelines, except for fluoride (F-) and turbidity in 4.3% and 36% of samples, respectively. Water quality index (WQI) classified samples (93%) as excellent and good quality (7%). Results showed maximum chronic daily intake values (0.14 ± 0.01 mg/kg-day) for nitrate (NO3-) and hazard quotient (0.80 ± 0.24) for F- in children via water intake from Upper Kachura and Shausar Lakes, respectively. Statistical analyses of Piper and Gibbs's plots revealed that the water quality is mainly characterized by bedrock geology.

The effects of lumbar stabilization exercises with and without jaw movements in non-specific low back pain (A randomized controlled trial).

Objective: This study aimed to investigate the added effect of jaw clenching on the efficacy of lumbar stabilization exercises to manage chronic non-specific low back pain. Methods: This randomized controlled trial was conducted at the Sindh Institute of Physical Medicine and Rehabilitation (SIPM&R) Karachi from April 2021 to April 2023. Eighty patients with chronic non-specific low back pain participated in this study. Forty patients each were randomly allocated to the lumbar stability exercise (LSE) group' and the lumbar stability exercise with teeth clenching (LSETC) group. Patients in both groups performed respective exercises twice weekly for 12 weeks. The Numeric Pain Rating Scale (NPRS), Roland Morris Disability Questionnaire (RMDQ), and Pressure Biofeedback Unit (PBU) were used to assess pain, disability, and muscle endurance respectively. Data were collected at the baseline, after six weeks and 12 weeks of intervention. A p-value of <0.05 was considered statistically significant. Results: Both groups showed statistically significant improvements in pain, disability, and muscle endurance. Upon further stratification, participants aged 20-30 years in the LSETC group showed significantly higher scores than the LSE group for NPRS, RMDQ, and PBU after 12 weeks. Overall, the LSETC group showed relatively higher improvement in mean scores for NPRS, RMDQ, and PBU than the LSE group. Conclusion: Lumbar stabilization exercises with and without jaw movement are effective for the treatment of chronic non-specific low back pain. The addition of teeth clenching enhanced the effectiveness of lumbar stability exercises, especially in young adults. Trial Registration: Clinicaltrials.gov (NCT04801212), Prospectively registered on March 16, 2021.

Anionic Synthetic Polymers Prevent Bacteriophage Infection.

Bioprocessing and biotechnology exploit microorganisms (such as bacteria) for the production of chemicals, biologics, therapies, and food. A major unmet challenge is that bacteriophage (phage) contamination compromises products and necessitates shut-downs and extensive decontamination using nonspecific disinfectants. Here we demonstrate that poly(acrylic acid) prevents phage-induced killing of bacterial hosts, prevents phage replication, and that induction of recombinant protein expression is not affected by the presence of the polymer. Poly(acrylic acid) was more active than poly(methacrylic acid), and poly(styrenesulfonate) had no activity showing the importance of the carboxylic acids. Initial evidence supported a virustatic, not virucidal, mechanism of action. This simple, low-cost, mass-produced additive offers a practical, scalable, and easy to implement solution to reduce phage contamination.

Under-Coordinated CoFe Layered Double Hydroxide Nanocages Derived from Nanoconfined Hydrolysis of Bimetal Organic Compounds for Efficient Electrocatalytic Water Oxidation.

Hierarchically structured bimetal hydroxides are promising for electrocatalytic oxygen evolution reaction (OER), yet synthetically challenging. Here, the nanoconfined hydrolysis of a hitherto unknown CoFe-bimetal-organic compound (b-MOC) is reported for the controllable synthesis of highly OER active nanostructures of CoFe layered double hydroxide (LDH). The nanoporous structures trigger the nanoconfined hydrolysis in the sacrificial b-MOC template, producing CoFe LDH core-shell octahedrons, nanoporous octahedrons, and hollow nanocages with abundant under-coordinated metal sites. The hollow nanocages of CoFe LDH demonstrate a remarkable turnover frequency (TOF) of 0.0505 s-1 for OER catalysis at an overpotential of 300 mV. It is durable in up to 50 h of electrolysis at step current densities of 10-100 mA cm-2 . Ex situ and in situ X-ray absorption spectroscopic analysis combined with theoretical calculations suggests that under-coordinated Co cations can bind with deprotonated Fe-OH motifs to form OER active Fe-O-Co dimmers in the electrochemical oxidation process, thereby contributing to the good catalytic activity. This work presents an efficient strategy for the synthesis of highly under-coordinated bimetal hydroxide nanostructures. The mechanistic understanding underscores the power of maximizing the amount of bimetal-dimer sites for efficient OER catalysis.

Identification of contributing factors, microorganisms and antimicrobial resistance involved in the complication of diabetic foot ulcer treatment.

Diabetic foot ulcer (DFU) is a neurological and peripherical complication of diabetes with unknown etiology that is often associated with polymicrobial infections. The present study was conducted to investigate the contributing factors in 285 DFU patients, which included 200 patients with diabetic foot infections (DFI). Identification and characterization of infecting bacterial isolates were done followed by assessment of their pattern of susceptibility to commonly used antibiotics. Among the studied subjects, type 2 diabetes mellitus (T2DM), ulcer type, depth, grade, loss of sensation, infection type, affected foot, recurrence, smoking status, Body Mass Index (BMI), and obesity levels revealed significant disease risk association. Ulcer grades 1 and 2 were more common in males while grade 3 in females. Recurrent infections were significantly higher in females (P = 0.03). Diabetic duration, hyperglycemia, ulcer type, infection type and BMI were positively correlated with delayed wound healing. In DFI samples, 40.2% consisted of gram-negative bacteria, with Pseudomonas aeruginosa (37.5%) being the most common, while in the 60% gram-positive isolates Staphylococcus aureus (40.5%) was the predominant species. Staphylococcus epidermidis was found more frequently in females (P = 0.05). The isolated bacterial strains presented higher resistance against the tested antibiotics; however, ceftriaxone was effective against most of the pathogens. In the current study T2DM along with diabetes duration, obesity, ulcer severity with polymicrobial infection was found to play a strong role in DFI development, where gender predisposition was also observed in ulcer grade and infection. DFI was correlated with loss of sensation, infection type, affected foot, smoking status, BMI and obesity levels.

High Molecular Weight Polyproline as a Potential Biosourced Ice Growth Inhibitor: Synthesis, Ice Recrystallization Inhibition, and Specific Ice Face Binding.

Ice-binding proteins (IBPs) from extremophile organisms can modulate ice formation and growth. There are many (bio)technological applications of IBPs, from cryopreservation to mitigating freeze-thaw damage in concrete to frozen food texture modifiers. Extraction or expression of IBPs can be challenging to scale up, and hence polymeric biomimetics have emerged. It is, however, desirable to use biosourced monomers and heteroatom-containing backbones in polymers for in vivo or environmental applications to allow degradation. Here we investigate high molecular weight polyproline as an ice recrystallization inhibitor (IRI). Low molecular weight polyproline is known to be a weak IRI. Its activity is hypothesized to be due to the unique PPI helix it adopts, but it has not been thoroughly investigated. Here an open-to-air aqueous N-carboxyanhydride polymerization is employed to obtain polyproline with molecular weights of up to 50000 g mol-1. These polymers were found to have IRI activity down to 5 mg mL-1, unlike a control peptide of polysarcosine, which did not inhibit all ice growth at up to 40 mg mL-1. The polyprolines exhibited lower critical solution temperature behavior and assembly/aggregation observed at room temperature, which may contribute to its activity. Single ice crystal assays with polyproline led to faceting, consistent with specific ice-face binding. This work shows that non-vinyl-based polymers can be designed to inhibit ice recrystallization and may offer a more sustainable or environmentally acceptable, while synthetically scalable, route to large-scale applications.

AIPs-SnTCN: Predicting Anti-Inflammatory Peptides Using fastText and Transformer Encoder-Based Hybrid Word Embedding with Self-Normalized Temporal Convolutional Networks.

Inflammation is a biologically resistant response to harmful stimuli, such as infection, damaged cells, toxic chemicals, or tissue injuries. Its purpose is to eradicate pathogenic micro-organisms or irritants and facilitate tissue repair. Prolonged inflammation can result in chronic inflammatory diseases. However, wet-laboratory-based treatments are costly and time-consuming and may have adverse side effects on normal cells. In the past decade, peptide therapeutics have gained significant attention due to their high specificity in targeting affected cells without affecting healthy cells. Motivated by the significance of peptide-based therapies, we developed a highly discriminative prediction model called AIPs-SnTCN to predict anti-inflammatory peptides accurately. The peptide samples are encoded using word embedding techniques such as skip-gram and attention-based bidirectional encoder representation using a transformer (BERT). The conjoint triad feature (CTF) also collects structure-based cluster profile features. The fused vector of word embedding and sequential features is formed to compensate for the limitations of single encoding methods. Support vector machine-based recursive feature elimination (SVM-RFE) is applied to choose the ranking-based optimal space. The optimized feature space is trained by using an improved self-normalized temporal convolutional network (SnTCN). The AIPs-SnTCN model achieved a predictive accuracy of 95.86% and an AUC of 0.97 by using training samples. In the case of the alternate training data set, our model obtained an accuracy of 92.04% and an AUC of 0.96. The proposed AIPs-SnTCN model outperformed existing models with an ∼19% higher accuracy and an ∼14% higher AUC value. The reliability and efficacy of our AIPs-SnTCN model make it a valuable tool for scientists and may play a beneficial role in pharmaceutical design and research academia.

Does the ultrasound imaging predict lower limb tendinopathy in athletes: a systematic review.

BACKGROUND: To conduct a systematic review looking into the possibility of US imaging to anticipate and identify future patellar or Achilles tendinopathy symptoms. METHODS: The studies that were taken into consideration for this review were prospective studies that employed baseline US imaging of the patellar OR Achilles tendons in asymptomatic patients and follow-up measures of pain and/or function. Two impartial reviewers evaluated the study's quality using the Critical Appraisal Skills Programme instrument. RESULTS: Participants in the included studies in this review came from various sports. The systematic review revealed a link between baseline tendon abnormalities in the US and a higher chance of developing both patellar and Achilles tendinopathy as well as their future occurrence. Nine of the included studies examined the patellar tendon alone, eight the patellar and Achilles tendon together, and four the Achilles tendon exclusively. For both tendons, US administration is done in a largely consistent manner. The tendon abnormalities of tendon thickness, hypoechogenicity and vascularity at baseline were associated with an increased risk of both Achilles and patellar tendinopathy. CONCLUSIONS: This systematic review shows that abnormal tendon structures seen by US in asymptomatic persons can predict the development of tendinopathy.

Low-Loss Paper-Substrate Triple-Band-Frequency Reconfigurable Microstrip Antenna for Sub-7 GHz Applications.

In this paper, a low-cost resin-coated commercial-photo-paper substrate is used to design a printed reconfigurable multiband antenna. The two PIN diodes are used mainly to redistribute the surface current that provides reconfigurable properties to the proposed antenna. The antenna size of 40 mm × 40 mm × 0.44 mm with a partial ground, covers wireless and mobile bands ranging from 1.91 GHz to 6.75 GHz. The parametric analysis is performed to achieve optimized design parameters of the antenna. The U-shaped and C-shaped emitters are meant to function at 2.4 GHz and 5.9 GHz, respectively, while the primary emitter is designed to operate at 3.5 GHz. The proposed antenna achieved peak gain and radiation efficiency of 3.4 dBi and 90%, respectively. Simulated and measured results of the reflection coefficient, radiation pattern, gain, and efficiency show that the antenna design is in favorable agreement. Since the proposed antenna achieved wideband (1.91-6.75 GHz) using PIN diode configuration, using this technique the need for numerous electronic components to provide multiband frequency is avoided.

Improvement of the Self-Controlled Hyperthermia Applications by Varying Gadolinium Doping in Lanthanum Strontium Manganite Nanoparticles.

In this study, silica-encapsulated gadolinium was doped in lanthanum strontium manganite nanoparticles (NPs) with different concentrations using the citrate-gel auto-combustion method. We focused on tuning the Curie temperature and enhancing the specific absorption rate (SAR) of silica-coated gadolinium-doped lanthanum strontium manganite NPs to make them suitable for self-controlled magnetic hyperthermia. The samples were characterized by using transmission electron microscopy (TEM), X-ray diffraction, Fourier transform infrared spectroscopy (FTIR), and magnetic measurements to examine the structural, optical, and magnetic properties of the manganite NPs. While our results exhibit a successful doping of gadolinium in lanthanum strontium manganite NPs, we further prepared magnetic core NPs with sizes between 20 and 50 nm. The Curie temperature of the NPs declined with increasing gadolinium doping, making them promising materials for hyperthermia applications. The Curie temperature was measured using the magnetization (M-T) curve. Magnetic heating was carried out in an external applied AC magnetic field. Our present work proved the availability of regulating the Curie temperature of gadolinium-doped lanthanum strontium manganite NPs, which makes them promising candidates for self-controlled magnetic hyperthermia applications.

Effects of thoracic spinal thrust manipulation for the management of shoulder impingement syndrome: Systematic review.

OBJECTIVE: To determine the effectiveness of thoracic spinal thrust manipulation for shoulder impingement syndrome in the improvement of pain, range of motion and functional outcomes. METHODS: The systematic review was conducted by 2 researchers independently using search strategy developed for different databases, including Cochrane Central register of control trials, PubMed, Pedro and MEDLINE, for relevant articles published between 2008 and 2020. The search strategy was designed for each database by combining the key terms and Boolean operators related to the review's objective. RESULTS: Of the 312 studies identified, 14(4.5%) were included. Of them, 4(28.6%) were in favour of thoracic thrust manipulation, 8(57.2%) did not support thoracic thrust manipulation as the sole treatment and 2(14.3%) favoured thoracic thrust manipulation along with exercises. CONCLUSIONS: Studies indicated immediate improvement in range of motion as well as pain after thrust manipulation, but others reported no such clinical difference. Manipulation should be combined with other exercise therapy to ensure some clinical improvement.

Substantiating the predictive role of ultrasound imaging in athletes with lower limb tendinopathy: a systematic review.

OBJECTIVE: To explore the potential of ultrasound imaging to anticipate and monitor future symptoms of patellar or Achilles' tendinopathy. METHODS: The systematic review comprised prospective studies that used ultrasound imaging of Achilles' OR patellar tendons in asymptomatic patients at baseline and measurements of pain and/or function at follow-up. The Critical Appraisal Skills Programme checklist used to assess study quality and it was done by two independent reviewers. RESULTS: Of the 19 studies reviewed, 9(47.3%) investigated patellar tendon alone, 6(31.5%) did both patellar and Achilles' tendon, and 4(21.2%) did Achilles tendon alone. The method of ultrasound administration was almost uniform for both the tendons. The studies showed that the use of ultrasound to predict lower limb tendinopathy was indefinite, but that a higher proportion of tendon disorganisation increased the risk of developing tendinopathy. In addition, promising results were obtained for the use of ultrasound in both Achilles' and patellar tendinopathy in monitoring the effect of load or treatment on tendon structure. CONCLUSIONS: The included studies had participants from different sports. Tendon irregularities at baseline on ultrasound were related to increased risk and future occurrence of both patellar and Achilles' tendinopathy. .

Effect of physical therapy treatment in infants treated for congenital muscular torticollis - a narrative review.

Congenital muscular torticollis is a problem that arises at birth or immediately after birth in which the sternocleidomastoid muscle is shortened on the afflicted side, leading to an ipsilateral rotated of the head and a contralateral rotation of the face and jaw. To determine the effectiveness of physical therapy treatment in infants treated for congenital muscular torticollis, relevant articles published between 2011 and 2020 were located using electronic databases. A total of 9 studies out of 24 potentially relevant articles were reviewed. All studies were randomised controlled trials with 6-8 score on the Physiotherapy Evidence Database scale (Pedro scale) which showed high quality of methodology. The studies typically found significant statistical effects in the management of congenital muscular torticollis. Additionally, most of the studies reported increased adherence to exercise as another essential advantage. Conservative physical therapy management showed positive outcomes, and early physiotherapy referral showed significant reduction in treatment duration.

Intrarater Reliability Of Cervical Range Of Motion Device Among Adults With And Without Chronic Non-Specific Neck Pain.

Objective: To evaluate the intrarater reliability of the cervical range of motion device among adults with and without chronic non-specific neck pain. METHODS: The analytical, cross-sectional study was conducted from January to March 2019 at the Sindh Institute of Physical Medicine and Rehabilitation, Karachi, and comprised healthy adults with no neck pain in the preceding 6 months in Group A, and adults of either gender with chronic non-specific neck pain for >3 months in Group B. The two groups were further divided into age groups 21-30 years, 31-40 years and 41-50 years. A cervical range of motion device was used to measure the range of flexion, extension, right and left lateral flexion and right and left rotation of all the subjects. The measurements were taken by a single tester on day-1 and day-3 to assess the intrarater reliability. Data was analysed using SPSS 26. RESULTS: Of the 60 subjects, there were 30(50%) in each of the two groups. Within the groups, there were 10(33.3%) subjects in each of the 3 age subgroups. Overall, there were 27(45%) males and 33(55%) females. In Group A, the intraclass correlation coefficient values for all cervical ranges were between 0.81 and 0.99, whereas in Group B, the values ranged from 0.64 to 0.88. The intraclass correlation coefficient values yielded good to excellent agreement in both groups (>0.75) except for left lateral flexion in Group B (p=0.64), and all the values were statistically significant (p<0.05). Conclusion: There was good to excellent intrarater reliability of cervical range of motion device in adults with and without chronic non-specific neck pain.

Eichhornia crassipes Ameliorated Rheumatoid Arthritis by Modulating Inflammatory Cytokines and Metalloproteinase Enzymes in a Rat Model.

Background and Objectives: This study was planned to investigate the anti-arthritic property of flowers of E. crassipes in a Sprague-Dawley rat model by administering Freund's Complete Adjuvant (FCA). Materials and Methods: Arthritis was induced at day 0 in all rats except negative controls, while arthritic progress and paw edema were analyzed on specific days (8th, 13th, 18th, and 23rd) via the macroscopic arthritic scale and a digital Vernier caliper, respectively. Histopathological parameters were examined using a Hematoxylin and Eosin (H&E) staining method. Blood samples were withdrawn from rats to investigate the effects of the E. crassipes flower on the mRNA expression values of inflammatory markers, via a reverse transcription PCR technique. Serum samples were used to determine prostaglandin E2 (PGE2) levels using enzyme-linked immunosorbent assay (ELISA). Values of alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine, and urea, besides hematological parameters, i.e., the hemoglobin (Hb) content and complete blood count (CBC), were investigated. Results: The data showed that E. crassipes inhibited the arthritic progress and ameliorated the paw edema. The amelioration of parameters assessed via the histopathological analysis of ankle joints, as well as via hematological analysis, confirmed the diminution of rheumatoid arthritis (RA) in the plant-treated groups. Treatment with E. crassipes inhibited the expression levels of tumor necrosis factor-α (TNF-α), interleukins (IL-1ß and IL-6), nuclear factor KappaB (NF-κB), matrix metalloproteinase (MMP-2 and MMP-3), and vascular endothelial growth factor (VEGF). Serum PGE2 levels were also found to be reduced in treatment groups. A biochemical investigation revealed the improvements in hepatic markers in plant-treated groups. The data indicated that the plant has no hepatotoxic or nephrotoxic effects at the studied dose. GC-MS (Gas Chromatography-Mass Spectrometry) analysis displayed the presence of phytochemicals having known anti-inflammatory and antioxidant properties. Conclusions: Therefore, it may be concluded that E. crassipes possesses anti-arthritic characteristics that could be attributed to the modulation of pro-inflammatory cytokines, MMPs, and PGE2 levels.

Amelioration of Rheumatoid Arthritis by Fragaria nubicola (Wild Strawberry) via Attenuation of Inflammatory Mediators in Sprague Dawley Rats.

Background and Objectives: Fragaria nubicola has never been evaluated scientifically for its anti-arthritic potential despite its use in folkloric systems of medicine. The research was conducted to assess the potential of F. nubicola against rheumatoid arthritis. Materials and Methods: The current study provided scientific evidence by evaluating the effects of plants using an in vivo CFA-induced model of arthritic rats and subsequent microscopic histopathological evaluation of ankle joints along with the determination of paw edema using a digital water displacement plethysmometer. The study also gave insight by determining levels of pro-inflammatory cytokines, matrix metalloproteinase enzymes (MMPs), prostaglandin E2 (PGE2), nuclear factor kappa B (NF-κB), vascular endothelial growth factor (VEGF), and biochemical and hematological parameters. GCMS analysis was also conducted for the identification of possible anti-inflammatory plant constituents. Results: The data showed that F. nubicola-treated groups attenuated the progression of arthritis and paw edema. Microscopic histopathological evaluation validated the anti-arthritic potential by showing amelioration of bone erosion, infiltration of inflammatory cells, and pannus formation. RT-PCR analysis displayed that treatment with F. nubicola down-regulated IL1ß, IL6, TNFα, NF-κB, VEGF, MMP2, MMP3, and MMP9 levels. Moreover, ELISA exhibited a reduction in levels of PGE2 levels in treatment groups. The levels of RBCs, platelets, WBCs, and Hb content were found to be nearly similar to negative control in the treated group. Statistically, a non-significant difference was found when all groups were compared for urea, creatinine, ALT, and AST analysis, indicating the safety of plant extract and fractions at test doses. GCMS analysis of extract and fractions showed the existence of many anti-inflammatory and antioxidant phytochemicals. Conclusion: In conclusion, F. nubicola possessed anti-arthritic properties that might be attributed to the amelioration of MMPs and pro-inflammatory cytokines.

Physiological, Pathological and Pharmacological Interactions of Hydrogen Sulphide and Nitric Oxide in the Myocardium of Rats with Left Ventricular Hypertrophy.

Left ventricular hypertrophy (LVH) is characterized by increased myocardium thickness due to increased oxidative stress and downregulation of cystathione γ lyase (CSE) endothelial nitric oxide synthase (eNOS). Upregulation of CSE by hydrogen sulphide (H2S) and ENOS by L-arginine can arrest the progression of LVH individually. The present study explored the combined treatment of H2S and NO in the progression of LVH, and demonstrated that the response is due to H2S, NO or formation of either new molecule in physiological, pathological, and pharmacological in vivo settings of LVH. Exogenous administration H2S+NO in LVH significantly reduced (all p < 0.05) systolic blood pressure (SBP) and mean arterial pressure (MAP), LV index, heart index and oxidative stress when compared to the LVH group. There was downregulation of CSE mRNA and eNOS in the heart, and exogenous administration of H2S+NO groups upregulated eNOS MRNA while CSE MRNA remained downregulated in the hearts of the LVH group. Similar trends were observed with concentrations of H2S and NO in the plasma and tissue. It can be concluded that combined treatment of LVH with H2S and NO significantly ameliorate the progression of LVH by attenuating systemic hemodynamic and physical indices, and by decreasing oxidative stress. Molecular expression data in the myocardium of LVH depicts that combined treatment upregulated eNOS/NO while it downregulated CSE/H2S pathways in in vivo settings, and it is always eNOS/NO pathways which play a major role.