Desloratadine via its anti-inflammatory and antioxidative properties ameliorates TNBS-induced experimental colitis in rats.

BACKGROUND: Intestinal mucosal immune cells, notably mast cells, are pivotal in ulcerative colitis (UC) pathophysiology. Its activation elevates tissue concentrations of histamine. Inhibiting colonic histamine release could be an effective therapeutic strategy for treating UC. Experimental model like 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats mimic human IBD, aiding treatment investigations. Drug repurposing is a promising strategy to explore new indications for established drugs. Desloratadine (DES) is second-generation antihistamine utilized for managing allergies by blocking histamine action in the body. It also has reported anti-inflammatory and antioxidant actions. OBJECTIVE: DES was investigated for its repurposing potential in UC by preclinical screening in TNBS-induced colitis in Wistar rats. METHODS: Therapeutic efficacy of DES was evaluated both individually and in combination with standard drug 5-aminosalicylicacid (5-ASA). Rats were orally administered DES (10 mg/kg), 5-ASA (25 mg/kg), and DES + 5-ASA (5 mg + 12.15 mg) following the induction of colitis. Parameters including disease activity score rate (DASR), colon/body weight ratio (CBWR), colon length, diameter, pH, histological injury, and scoring were evaluated. Inflammatory biomarkers such as IL-1ß, TNF-α, along with reduced glutathione (GSH), and malondialdehyde (MDA) were assessed. RESULTS: Significant protective effects of DES, especially in combination with 5-ASA, against TNBS-induced inflammation were observed as evidenced by reduced DASR, CBWR, and improved colon morphology. Drugs significantly lowered plasma and colon histamine and, cytokines levels. GSH restoration, and decreased MDA content were also observed. CONCLUSION: DES and DES + 5-ASA demonstrated potential in alleviating colonic inflammation associated with TNBS-induced colitis in rats. The effect can be attributed to its antihistamine, anticytokine, and antioxidative properties.

Near-Temperature-Independent Electron Transport Well beyond Expected Quantum Tunneling Range via Bacteriorhodopsin Multilayers.

A key conundrum of biomolecular electronics is efficient electron transport (ETp) through solid-state junctions up to 10 nm, often without temperature activation. Such behavior challenges known charge transport mechanisms, especially via nonconjugated molecules such as proteins. Single-step, coherent quantum-mechanical tunneling proposed for ETp across small protein, 2-3 nm wide junctions, but it is problematic for larger proteins. Here we exploit the ability of bacteriorhodopsin (bR), a well-studied, 4-5 nm long membrane protein, to assemble into well-defined single and multiple bilayers, from ∼9 to 60 nm thick, to investigate ETp limits as a function of junction width. To ensure sufficient signal/noise, we use large area (∼10-3 cm2) Au-protein-Si junctions. Photoemission spectra indicate a wide energy separation between electrode Fermi and the nearest protein-energy levels, as expected for a polymer of mostly saturated components. Junction currents decreased exponentially with increasing junction width, with uniquely low length-decay constants (0.05-0.5 nm-1). Remarkably, even for the widest junctions, currents are nearly temperature-independent, completely so below 160 K. While, among other things, the lack of temperature-dependence excludes, hopping as a plausible mechanism, coherent quantum-mechanical tunneling over 60 nm is physically implausible. The results may be understood if ETp is limited by injection into one of the contacts, followed by more efficient charge propagation across the protein. Still, the electrostatics of the protein films further limit the number of charge carriers injected into the protein film. How electron transport across dozens of nanometers of protein layers is more efficient than injection defines a riddle, requiring further study.

Re-emerging human monkeypox: A major public-health debacle.

A multicountry outbreak of the monkeypox virus has gained global attention. As of May 25, 250 confirmed human monkeypox cases have been reported globally. Monkeypox is caused by the Monkeypox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. Monkeypox is often a self-limiting infection, with symptoms lasting 2-4 weeks with the case fatality ratio around 3%-6%. Monkeypox is transmitted to humans by direct contact with an infected person or animal or contact with virus-contaminated material. Human monkeypox infections may lead to various medical complications such as fever, rash, and lymphadenopathies. Pneumonitis, encephalitis, sight-threatening keratitis, and subsequent bacterial infections are all possible complications of monkeypox. An antiviral agent developed to treat smallpox has also been approved for use in the treatment of monkeypox in the United States. Vaccines used in the smallpox eradication program also provided immunity to monkeypox. Newer vaccines have been developed, one of which has been approved for monkeypox prevention. In this study, we provide information about the recent outbreaks of human monkeypox, epidemiology, transmission pattern, possible diagnosis techniques, therapeutics, and available preventive strategies.

Antiviral and anti-inflammatory activity of natural compounds against Japanese encephalitis virus via inhibition of NS5 protein and regulation of key immune and inflammatory signaling pathways.

Japanese encephalitis virus (JEV) is the foremost cause of viral encephalitis in Southeast Asia and Australia leading to approximately 68 000 clinical cases and about 13 600-20 400 deaths annually. Vaccination is not completely sure and safe. Despite this, no specific antiviral has been available or approved for JEV infection yet and treatment is generally symptomatic. Therefore, this study aims to examine the antiviral activity of natural compounds against JEV proteins. The antiviral activity of natural compounds was investigated via molecular docking, cytopathic effect (CPE) inhibition assay, western blotting, and indirect immunofluorescence assay. Physiochemical, pharmacokinetics, and toxicity analysis were evaluated for the safety and efficacy of natural compounds. Network pharmacology-based approaches have been used to study the molecular mechanisms of drug-target interactions. Molecular docking results suggested that the NS5 protein of JEV is the major target for natural compounds. Network pharmacology-based analysis revealed that these drugs majorly target IL6, AKT1, tumor necrosis factor (TNF), and PTGS2 to regulate key immune and inflammatory pathways such as nuclear factor kappa B, PI3K-Akt, and TNF signaling, during JEV infection. Our in vitro results show that among the natural compounds, curcumin provides the highest protection against JEV infection via reducing the JEV-induced CPE (IC50 = 5.90 ± 0.44 µM/mL), and reduces the expression of NS5 protein, IL6, AKT1, TNF-α, and PTGS2. However, other natural compounds also provide protection to some extent but their efficacy is lower compared to curcumin. Therefore, this study shows that natural compounds, mainly curcumin, may offer novel therapeutic avenues for the treatment of JEV via inhibiting key viral proteins and regulating crucial host pathways involved in JEV replication.

Pre-clinical investigation of protective effect of nutraceutical D-glucosamine on TNBS-induced colitis.

OBJECTIVE: The level of precursors involved in the biosynthesis of glycosaminoglycan (GAG), glucosamine synthase, and N-acetyl glucosamine (NAG), are significantly reduced in inflammatory bowel disease (IBD). This results in deficient GAG content in mucosa, which eventually disrupt the gut wall integrity, provoking abnormal immunological responses. This is characterized by colossal liberation of inflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukins (ILs), and reactive oxygen species (ROS) provoking colonic inflammation. D-glucosamine (D-GLU) is reported to suppress oxidative stress, and pro-inflammatory cytokines and acts as a starting material for biosynthesis of NAG. The potential of D-GLU and its combination with mesalamine (5-ASA) was investigated in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-instigated IBD in Wistar rats. MATERIALS AND METHODS: Standard and test drugs were given orally for 5 d to separate groups of rats. Colonic inflammation was evaluated by disease activity score rate (DASR), colon/body weight ratio, colon length, diameter, colon pH, histological injury, and score. Inflammatory biomarkers IL-1ß, TNF-α, along with reduced glutathione (GSH), and malondialdehyde (MDA) were assessed. RESULTS: Combination of D-GLU + 5-ASA significantly ameliorated severity of colonic inflammation by lowering DASR (p < 0.001) and colon/body weight ratio (p < 0.001), restored the colonic architecture and suppressed the histopathological score (p < 0.001), along with the absence of major adverse reactions. The combination suppressed the levels of inflammatory markers (p < 0.001) and MDA (p < 0.001) while enhancing GSH level (p < 0.001). CONCLUSION: In comparison to individual 5-ASA and D-GLU, combination of drugs significantly diminished colitis severity through their combined anti-inflammatory and antioxidant effects by acting on multiple targets simultaneously. The combination holds remarkable potential in the management of IBD.

Raman Spectroscopy as a Simple yet Effective Analytical Tool for Determining Fermi Energy and Temperature Dependent Fermi Shift in Silicon.

The Fermi energy is known to be dependent on doping and temperature, but finding its value and corresponding thermal Fermi shift experimentally is not only difficult but is virtually impossible if one attempts their simultaneous determination. We report that temperature dependent Raman spectromicroscopy solves the purpose easily and proves to be a powerful technique to determine the position and temperature associated Fermi shift in an extrinsic semiconductor as demonstrated for silicon in the present study. The typical asymmetrically broadened Raman spectral line-shape from sufficiently doped n- and p-type silicon contains the information about the Fermi level position through its known association with the Fano coupling strength. Thus, Raman line-shape parameters, the terms quantify the Fano-coupling, have been used as experimental observables to reveal the value of the Fermi energy and consequent thermal Fermi shift. A simple formula has been developed based on existing established theoretical frameworks that can be used to calculate the position of the Fermi level. The proposed Raman spectroscopy-based formulation applies well for n- and p-type silicon. The calculated Fermi level position and its temperature dependent variation are consistent with the existing reports.

Transmission dynamics and mutational prevalence of the novel Severe acute respiratory syndrome coronavirus-2 Omicron Variant of Concern.

The novel Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variant, Omicron (PANGO lineage B.1.1.529) is being reported from all around the world. The WHO has categorized Omicron as a Variant of Concern (VOC) considering its higher transmissibility and infectivity, vaccine breakthrough cases. As of January 6, 2022, Omicron has been reported in at least 149 countries. Therefore, this study was planned to investigate the transmission dynamics and mutational prevalence of the novel SARS-CoV-2 Omicron variant. The transmission dynamics and Omicron SARS-CoV-2 divergence was studied using GISAID and Nextstrain which provides information about the genetic sequences, epidemiological, geographical, and species-specific data of human, avian, and animal viruses. Further, the mutation prevalence in spike glycoprotein of Omicron was studied, and the frequency of the crucial mutations was compared with the other prevalent VOCs. The transmission dynamics suggest that the Omicron was first identified in South Africa and then it was reported in the United Kingdom followed by the United States and Australia. Further, our phylogenetic analysis suggests that Omicron (BA.1) was clustered distinctly from the other VOCs. In the Spike glycoprotein, the Omicron (B.1.1.529) demonstrates critical 32 amino acid changes. This study may help us to understand mutational hotspots, transmission dynamics, phylogenetic divergence, effect on testing and immunity, which shall promote the progress of the clinical application and basic research.

Characterization of the novel SARS-CoV-2 Omicron (B.1.1.529) variant of concern and its global perspective.

As the latest identified novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC), the influence of Omicron on our globe grows promptly. Compared with the last VOC (Delta variant), more mutations were identified, which may address the characteristics of Omicron. Considering these crucial mutations and their implications including an increase in transmissibility, COVID-19 severity, and reduction of efficacy of currently available diagnostics, vaccines, and therapeutics, Omicron has been classified as one of the VOC. Notably, 15 of these mutations reside in the receptor-binding domain of spike glycoprotein, which may alter transmissibility, infectivity, neutralizing antibody escape, and vaccine breakthrough cases of COVID-19. Therefore, our present study characterizes the mutational hotspots of the Omicron variant in comparison with the Delta variant of SARS-CoV-2. Furthermore, detailed information was analyzed to characterize the global perspective of Omicron, including transmission dynamic, effect on testing, and immunity, which shall promote the progress of the clinical application and basic research. Collectively, our data suggest that due to continuous variation in the spike glycoprotein sequences, the use of coronavirus-specific attachment inhibitors may not be the current choice of therapy for emerging SARS-CoV-2 VOCs. Hence, we need to proceed with a sense of urgency in this matter.

Tracing the origin of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): A systematic review and narrative synthesis.

The aim of the study was to trace and understand the origin of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through various available literatures and accessible databases. Although the world enters the third year of the coronavirus disease 2019 pandemic, health and socioeconomic impacts continue to mount, the origin and mechanisms of spill-over of the SARS-CoV-2 into humans remain elusive. Therefore, a systematic review of the literature was performed that showcased the integrated information obtained through manual searches, digital databases (PubMed, CINAHL, and MEDLINE) searches, and searches from legitimate publications (1966-2022), followed by meta-analysis. Our systematic analysis data proposed three postulated hypotheses concerning the origin of the SARS-CoV-2, which include zoonotic origin (Z), laboratory origin (L), and obscure origin (O). Despite the fact that the zoonotic origin for SARS-CoV-2 has not been conclusively identified to date, our data suggest a zoonotic origin, in contrast to some alternative concepts, including the probability of a laboratory incident or leak. Our data exhibit that zoonotic origin (Z) has higher evidence-based support as compared to laboratory origin (L). Importantly, based on all the studies included, we generated the forest plot with 95% confidence intervals (CIs) of the risk ratio estimates. Our meta-analysis further supports the zoonotic origin of SARS/SARS-CoV-2 in the included studies.

Structural and molecular perspectives of SARS-CoV-2.

Recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transpired into pandemic coronavirus disease 2019 (COVID-19). SARS-CoV-2 has been rapidly transmitted across the globe within a short period of time, with more than 106 million cases and 2.3 million deaths. The continuous rise in worldwide cases of COVID-19, transmission dynamics of SARS-CoV-2 including re-infections and enormous case-fatality rates emphasizes the urgent need of potential preventive and therapeutic measures. The development of effective therapeutic and preventive measures relies on understanding the molecular and cellular mechanism of replication exhibited by SARS-CoV-2. The structure of SARS-CoV-2 is ranging from 90-120 nm that comprises surface viral proteins including spike, envelope, membrane which are attached in host lipid bilayer containing the helical nucleocapsid comprising viral RNA. Spike (S) glycoprotein initiates the attachment of SARS-CoV-2 with a widely expressed cellular receptor angiotensin-converting enzyme 2 (ACE2), and subsequent S glycoprotein priming via serine protease TMPRSS2. Prominently, comprehensive analysis of structural insights into the crucial SARS-CoV-2 proteins may lead us to design effective therapeutics molecules. The present article, emphasizes the molecular and structural perspective of SARS-CoV-2 including mechanistic insights in its replication.

Therapeutic approaches for SARS-CoV-2 infection.

Therapeutic approaches to COVID-19 treatment require appropriate inhibitors to target crucial proteins of SARS-CoV-2 replication machinery. It's been approximately 12 months since the pandemic started, yet no known specific drugs are available. However, research progresses with time in terms of high throughput virtual screening (HTVS) and rational design of repurposed, novel synthetic and natural products discovery by understanding the viral life cycle, immuno-pathological and clinical outcomes in patients based on host's nutritional, metabolic, and lifestyle status. Further, complementary and alternative medicine (CAM) approaches have also improved resiliency and immune responses. In this article, we summarize all the therapeutic antiviral strategies for COVID-19 drug discovery including computer aided virtual screening, repurposed drugs, immunomodulators, vaccines, plasma therapy, various adjunct therapies, and phage technology to unravel insightful mechanistic pathways of targeting SARS-CoV-2 and host's intrinsic, innate immunity at multiple checkpoints that aid in the containment of the disease.

Ion-Assisted Resonant Injection and Charge Storage in Carbon-Based Molecular Junctions.

Resonant injection and resulting charge storage were examined in a large-area carbon/tetraphenylporphyrin(TPP)/LiF/carbon junction, where the LiF layer provides mobile ions in acetonitrile (ACN) vapor. Resonant electron transfer into TPP molecules occurs at <+1 V in the presence of mobile ions, enabled by ionic screening of the carbon electrode. Injection of holes, i.e. formation of the TPP radical cation, inside the junction was monitored by in situ photocurrent measurements. Following the injection, despite the lack of a redox counter-reaction or conventional electrolyte, persistent faradaic current peaks dominate the IV cycle of the junction (±2 V) in ACN vapor, enhancing the reversible charge storage by a factor of 78 compared to that in vacuum.

Photostimulated Near-Resonant Charge Transport over 60 nm in Carbon-Based Molecular Junctions.

The bias and temperature dependence of both dark and photoinduced currents in carbon-based molecular junctions were examined over a wide range of oligomeric layer thickness (d) values from 4 to 60 nm. The dark current density versus bias (JV) response of nitroazobenzene molecular junctions exhibits the exponential thickness dependence consistent with coherent tunneling when d < 5 nm, but becomes weakly dependent on d and temperature (T) for d = 15-60 nm. The photocurrent (PC) response is orders of magnitude higher than the dark current for the same d and bias, with very different curve shape and much earlier onset with bias. Although the dark and PC differed greatly in magnitude for d > 14 nm, they both exhibit near zero attenuation coefficients (ß < 0.05 nm-1) and are activationless (Eact < 5 meV) below ∼200 K. For d > 14 nm, both dark and PC become electric field (E) dependent and exhibit approximate overlap of J versus E response for d = 14-60 nm. The value of ln J versus E1/2 is linear for both PC and dark current, with very different magnitudes and slopes. We propose an orbital mediated transport for PC, which involves sequential tunneling of photogenerated electrons and holes between frontier orbitals of adjacent, weakly interacting oligomeric subunits. Such transport is "bulk-limited", E dependent, and nearly activationless due to small tunneling barriers and short distances between adjacent molecular orbitals. In contrast, the dark current is activated and injection limited due to an interfacial energy barrier much larger than that for bulk transport in the junction interior. Rapid, low-barrier transport between orbitals in adjacent molecules should significantly extend the "range" of molecular electronics to >50 nm and avoid the usually strong temperature dependence observed in thicker organic films.

Comment on "Extent of conjugation in diazonium-derived layers in molecular junction devices determined by experiment and modelling" by C. Van Dyck, A. J. Bergren, V. Mukundan, J. A. Fereiro and G. A. DiLabio, Phys. Chem. Chem. Phys., 2019, 21, 16762.

Misinterpretation of scanning tunnelling microscopy results yielded incorrect conclusions about the flatness of a carbon electrode substrate used for molecular electronic devices. Furthermore, the results are not supported statistically and likely not representative of materials used in numerous publications.

Hydroxyapatite-collagen augments osteogenic differentiation of dental pulp stem cells.

The objectives of this study were to isolate and culture dental pulp stem cells (DPSCs) and to investigate their proliferation and osteogenic differentiation on hydroxyapatite-collagen (HA-Col) scaffold. DPSCs were characterized by fluorescence-activated cell sorting (FACS). Cultured cells were CD73+, CD90+, CD105+ and CD31-, CD45-. A commercially available HA-Col scaffold was used for culture of DPSCs. Cell attachment and viability of DPSCs cultured on scaffold was studied by sulforhodamine assay. Osteoblast differentiation capacity was studied by alkaline phosphatase assay and the effects of growth factors such as PDGF, IGF1 and FGF2 were further studied. Scanning electron microscopy (SEM) of cell seeded scaffolds was also performed. We found that DPSCs cultured exhibited the characteristic mesenchymal stem cells (MSCs) morphology and differentiation properties. Scaffold was found to be non-cytotoxic and had good biocompatibility in vitro. Osteoblast differentiation ability was found to increase at higher concentration of scaffold and additive effects were observed with the use of growth factors. In SEM, cells appeared to cover the entire surface of the scaffold forming continuous cell layer and extending filopodial extensions. HA-Col scaffold is apt for MSCs attachment and proliferation in vitro. Their unique self-renewal and multilineage differential potential make them ideal for use in regenerative medicine. The limitations of currently available bone graft materials have led to the emergence of tissue engineering using mesenchymal stem cells (MSCs). Since, HA-Col scaffold potentiated the proliferation and osteogenic differentiation of DPSCs, this biomimetic material may be an ideal one for maxillofacial and alveolar bone regeneration.

Deconvoluting Diffuse Reflectance Spectra for Retrieving Nanostructures' Size Details: An Easy and Efficient Approach.

A new model has been reported here to estimate the mean size and size distribution in nanostructured materials by utilizing a simple and economic diffuse reflectance spectroscopy through spectral line-shape analysis. In the proposed model, a theoretical line shape has been derived by taking into account a size distribution function, which represents a variation in absorption coefficient as a function of size, which in turn depends on the band gap and thus on the excitation photon energy. A fitting of the experimental absorption spectra with the derived line-shape function yields the mean crystallite size and size distribution. The size and size distribution have been successfully estimated from two different silicon nanostructured samples, prepared by metal induced etching. The model has been validated by comparing the estimated values with the sizes estimated using Raman spectroscopy, which is a well-known technique. The two results are not only consistent with each other but are also found to be consistent with the electron microscopy's results, revealing that a technique as simple and as economic as diffuse reflectance spectroscopy can be used to estimate size distribution. In addition, the proposed model can also be used to investigate the homogeneity in the size distribution in a nanostructured sample.

Quantifying the Short-Range Order in Amorphous Silicon by Raman Scattering.

Quantification of the short-range order in amorphous silicon has been formulized using Raman scattering by taking into account established frameworks for studying the spectral line-shape and size dependent Raman peak shift. A theoretical line-shape function has been proposed for representing the observed Raman scattering spectrum from amorphous-Si-based on modified phonon confinement model framework. While analyzing modified phonon confinement model, the term "confinement size" used in the context of nanocrystalline Si was found analogous to the short-range order distance in a-Si thus enabling one to quantify the same using Raman scattering. Additionally, an empirical formula has been proposed using bond polarizability model for estimating the short-range order making one capable to quantify the distance of short-range order by looking at the Raman peak position alone. Both the proposals have been validated using three different data sets reported by three different research groups from a-Si samples prepared by three different methods making the analysis universal.

Spectroscopic Evidence of Phosphorous Heterocycle-DNA Interaction and its Verification by Docking Approach.

In the present work, the interaction of phosphorous heterocycle (PH) with calf thymus DNA (CTDNA) has been studied using spectroscopy and verified by molecular modeling which is found to be in consonance with each other. Apparent association constant (Kapp = 4.77 × 103 M- 1), calculated using UV-Vis spectra indicating an adequate complex formation between CTDNA and PH. A dynamic mode of the fluorescence quenching mechanism in case of ethidium bromide (EB) + CTDNA by PH has been observed confirming formation of DNA-PH complex. A moderate binding constants of PH with CTDNA + EB has been observed (2.74 × 104 M- 1 at 293 K) by means of fluorescence data. Calculated values of thermodynamic parameters enthalpy change (ΔH) and entropy change (ΔS), suggests weak (van der Walls like) force and hydrogen bonds playing the main role in the binding of PH to CTDNA. Furthermore, the results of circular dichroism (CD) reveal that PH does not disturb native conformation of CTDNA. As observed from absorption and fluorescence spectroscopy the binding mode of PH with DNA was indicative of a non-intercalative binding, which was supposed to be a groove binding. The molecular modeling results show that PH is capable of binding DNA having docking binding energy = -7.26 kcal × mol- 1. Above mentioned experimental results are found to be in consonance with molecular docking simulations and supports the CTDNA-PH binding. Graphical Abstract.

General Parenting Strategies: Practical Suggestions for Common Child Behavior Issues.

Parents often seek guidance from physicians on child behavior problems. Questions may range from general parenting strategies to managing specific child behaviors. Physicians and their staff can identify problematic parent-child interactions or behaviors within the office setting and assist parents by providing effective monitoring tools for behavior problems. Effective strategies for influencing a child's behavior include positive reinforcement to increase appropriate behavior, extinction (planned ignoring) for most low-level problematic behaviors, and time-out from reinforcement for more problematic behaviors. Written contracting provides parents the opportunity to communicate with their children about important behaviors and strengthens the commitment of each party to improve behavior. Parents should be cautioned about the use of punishment (e.g., scolding, taking away privileges or possessions) because it suppresses behavior only temporarily. Physicians should discourage physical or corporal punishment because it is related to negative parent-child relationships, increased aggressiveness, antisocial behavior, lower cognitive ability, lower self-esteem, mental health problems, and increased risk of physical abuse.

Room-Temperature Magneto-dielectric Effect in LaGa0.7Fe0.3O3+γ; Origin and Impact of Excess Oxygen.

We report an observation of room-temperature magneto-dielectric (RTMD) effect in LaGa0.7Fe0.3O3+γ compound. The contribution of intrinsic/resistive sources in the presently observed RTMD effect was analyzed by measuring direct-current (dc) magnetoresistance (MR) in four-probe geometry and frequency-dependent MR via impedance spectroscopy (MRIS). Present MRIS analysis reveals that at frequencies corresponding to grain contribution (≥1 × 106 Hz for present sample), the observed MD phenomenon is MR-free/intrinsic, whereas at lower probing frequencies (<1 × 106 Hz), the observed MD coupling appears to be MR-dominated possibly due to oxygen excess, that is, due to coexistence of Fe3+ and Fe4+. The magnetostriction is anticipated as a mechanism responsible for MR-free/intrinsic MD coupling, whereas the MR-dominated part is attributed to hopping charge transport along with Maxwell-Wagner and space charge polarization. The multivalence of Fe ions in LaGa0.7Fe0.3O3+γ was validated through iodometric titration and Fe K-edge X-ray absorption near-edge structure measurements. The excess of oxygen, that is, coexistence of Fe3+ and Fe4+, was understood in terms of stability of Fe4+ by means of "bond-valence-sum" analysis and density functional theory-based first-principles calculations. The cation vacancies at La/Ga site (or at La and Ga both) were proposed as the possible origin of excess oxygen in presently studied compound. Present investigation suggests that, to justify the intrinsic/resistive origin of MD phenomenon, frequency-dependent MR measurements are more useful than measuring only dc MR or comparing the trends of magnetic-field-dependent change in dielectric constant and tan δ. Presently studied Fe-doped LaGaO3 can be a candidate for RTMD applications.