Herbal Interactions with Cardiac Medications: A Comprehensive Review of Potential Interactions between Herbal Drugs and Commonly Prescribed Cardiac Medications.

BACKGROUND: The concomitant use of herbal remedies in conjunction with conventional cardiac medications has increased significantly in recent years, primarily due to improvements in the quality standards of herbal medicines and the pervasive belief that natural products pose no harm to the human body. Contrary to this belief, multiple phytoconstituents found in herbal products have the potential to interact with conventional cardiac drugs, potentially resulting in severe adverse effects.

Objective: This review aimed to elucidate the intricacies of these interactions highlighting herbal medications that interact with established pharmaceuticals used for the treatment of cardiovascular disorders. Moreover, the review draws attention to safety concerns and preventative steps that should be taken by patients and medical professionals.. This endeavor is vital to avert adverse events stemming from such interactions.

Methods: Our approach entailed a comprehensive literature review employing keywords such as "mechanisms of herb-drug interactions," "herbal medications," and "cardiovascular disorders." The drugs presented in this review were selected based on their popularity among the general population, frequency of their employability, and potential to manifest drug interactions. We sourced pertinent information from reputable databases, including PubMed, Scopus, and Elsevier.

Results: Heart or blood vessel disorders are referred to as cardiovascular diseases (CVDs), which include conditions such as heart failure, stroke, hypertensive heart disease, and peripheral arterial disease. The primary underlying factor for the development of CVDs is dyslipidemia, which can be treated with classical antihyperlipidemic drugs such as statins, ezetimibe, and PCSK9-inhibitors. The use of herbal remedies is often unregulated, and there is a lack of scientific evidence supporting their use, particularly in the management of heart failure. Patients may not disclose their use of herbal remedies to health care practitioners, which can result in potential harm.

Conclusion: Uncontrolled dyslipidemia leads to hypercholesterolemia, which can result in atherosclerotic plaques and blocked arteries and veins. Herbal remedies and botanical products are also used to prevent or treat illnesses, and many prescription pharmaceuticals are made from plant compounds. Herbal remedies are often preferred because of the belief that they are safe and have no potential to cause harm. However, there is insufficient scientific data to support the use of herbal remedies, especially when treating heart disease. Using herbal remedies in conjunction with medicinal pharmaceuticals may result in unfavorable effects.

Methionine sulfoxide reductase 2 regulates Cvt autophagic pathway by altering the stability of Atg19 and Ape1 in Saccharomyces cerevisiae.

The reversible oxidation of methionine plays a crucial role in redox regulation of proteins. Methionine oxidation in proteins causes major structural modifications that can destabilize and abrogate their function. The highly conserved methionine sulfoxide reductases protect proteins from oxidative damage by reducing their oxidized methionines, thus restoring their stability and function. Deletion or mutation in conserved methionine sulfoxide reductases leads to aging and several human neurological disorders and also reduces yeast growth on nonfermentable carbon sources. Despite their importance in human health, limited information about their physiological substrates in humans and yeast is available. For the first time, we show that Mxr2 interacts in vivo with two core proteins of the cytoplasm to vacuole targeting (Cvt) autophagy pathway, Atg19, and Ape1 in Saccharomyces cerevisiae. Deletion of MXR2 induces instability and early turnover of immature Ape1 and Atg19 proteins and reduces the leucine aminopeptidase activity of Ape1 without affecting the maturation process of Ape1. Additonally, Mxr2 interacts with the immature Ape1, dependent on Met17 present within the propeptide of Ape1 as a single substitution mutation of Met17 to Leu abolishes this interaction. Importantly, Ape1 M17L mutant protein resists oxidative stress-induced degradation in WT and mxr2Δ cells. By identifying Atg19 and Ape1 as cytosolic substrates of Mxr2, our study maps the hitherto unexplored connection between Mxr2 and the Cvt autophagy pathway and sheds light on Mxr2-dependent oxidative regulation of the Cvt pathway.

First Simultaneous Determination of Inclusive and Exclusive |V_{ub}|.

The first simultaneous determination of the absolute value of the Cabibbo-Kobayashi-Maskawa matrix element V_{ub} using inclusive and exclusive decays is performed with the full Belle data set at the ϒ(4S) resonance, corresponding to an integrated luminosity of 711 fb^{-1}. We analyze collision events in which one B meson is fully reconstructed in hadronic modes. This allows for the reconstruction of the hadronic X_{u} system of the semileptonic b→uℓν[over ¯]_{ℓ} decay. We separate exclusive B→πℓν[over ¯]_{ℓ} decays from other inclusive B→X_{u}ℓν[over ¯]_{ℓ} and backgrounds with a two-dimensional fit that utilizes the number of charged pions in the X_{u} system and the four-momentum transfer q^{2} between the B and X_{u} systems. Combining our measurement with information from lattice QCD and QCD calculations of the inclusive partial rate as well as external experimental information on the shape of the B→πℓν[over ¯]_{ℓ} form factor, we determine |V_{ub}^{excl}|=(3.78±0.23±0.16±0.14)×10^{-3} and |V_{ub}^{incl}|=(3.88±0.20±0.31±0.09)×10^{-3}, respectively, with the uncertainties being the statistical error, systematic errors, and theory errors. The ratio of |V_{ub}^{excl}|/|V_{ub}^{incl}|=0.97±0.12 is compatible with unity.

Search for a Heavy Neutrino in τ Decays at Belle.

We report on a search for a heavy Majorana neutrino in the decays τ^{-}→π^{-}ν_{h}, ν_{h}→π^{±}ℓ^{∓}, ℓ=e, µ. The results are obtained using the full data sample of 988 fb^{-1} collected with the Belle detector at the KEKB asymmetric energy e^{+}e^{-} collider, which contains 912×10^{6} ττ pairs. We observe no significant signal and set 95% CL upper limits on the couplings of the heavy right-handed neutrinos to the conventional standard model left-handed neutrinos in the mass range 0.2-1.6 GeV/c^{2}. This is the first study of a mixed couplings of heavy neutrinos to τ leptons and light-flavor leptons.

Precise Measurement of the D_{s}

We measure the lifetime of the D_{s}^{+} meson using a data sample of 207 fb^{-1} collected by the Belle II experiment running at the SuperKEKB asymmetric-energy e^{+}e^{-} collider. The lifetime is determined by fitting the decay-time distribution of a sample of 116×10^{3} D_{s}^{+}→ϕπ^{+} decays. Our result is τ_{D_{s}^{+}}=(499.5±1.7±0.9) fs, where the first uncertainty is statistical and the second is systematic. This result is significantly more precise than previous measurements.

Tests of Light-Lepton Universality in Angular Asymmetries of B

We present the first comprehensive tests of the universality of the light leptons in the angular distributions of semileptonic B^{0}-meson decays to charged spin-1 charmed mesons. We measure five angular-asymmetry observables as functions of the decay recoil that are sensitive to lepton-universality-violating contributions. We use events where one neutral B is fully reconstructed in ϒ(4S)→BB[over ¯] decays in data corresponding to 189 fb^{-1} integrated luminosity from electron-positron collisions collected with the Belle II detector. We find no significant deviation from the standard model expectations.

Search for a τ

We report the first search for a nonstandard-model resonance decaying into τ pairs in e^{+}e^{-}→µ^{+}µ^{-}τ^{+}τ^{-} events in the 3.6-10 GeV/c^{2} mass range. We use a 62.8 fb^{-1} sample of e^{+}e^{-} collisions collected at a center-of-mass energy of 10.58 GeV by the Belle II experiment at the SuperKEKB collider. The analysis probes three different models predicting a spin-1 particle coupling only to the heavier lepton families, a Higgs-like spin-0 particle that couples preferentially to charged leptons (leptophilic scalar), and an axionlike particle, respectively. We observe no evidence for a signal and set exclusion limits at 90% confidence level on the product of cross section and branching fraction into τ pairs, ranging from 0.7 to 24 fb, and on the couplings of these processes. We obtain world-leading constraints on the couplings for the leptophilic scalar model for masses above 6.5 GeV/c^{2} and for the axionlike particle model over the entire mass range.

Measurement of CP Violation in B

We report a measurement of the CP-violating parameters C and S in B^{0}→K_{S}^{0}π^{0} decays at Belle II using a sample of 387×10^{6} BB[over ¯] events recorded in e^{+}e^{-} collisions at a center-of-mass energy corresponding to the ϒ(4S) resonance. These parameters are determined by fitting the proper decay-time distribution of a sample of 415 signal events. We obtain C=-0.04_{-0.15}^{+0.14}±0.05 and S=0.75_{-0.23}^{+0.20}±0.04, where the first uncertainties are statistical and the second are systematic.

A comparative study of rectal volume variation in patients with prostate cancer: A tertiary care center study.

INTRODUCTION: Every day variations in rectal filling in prostate cancer radiotherapy can significantly alter the delivered dose distribution from what was intended. The goal of this study was to see if the time of treatment delivery affected the rectal filling. METHODS: This is a retrospective study which included 50 patients with localized prostate cancer treated with volumetric modulated arc therapy (VMAT) to the primary and regional lymph nodes. Cone Beam Computed Tomography (CBCT) image-sets were done for all patient's daily setup verification. The radiation therapist contoured the rectum on all CBCT image sets. The rectal volumes delineated on CBCT and the planning CT image sets were compared. The change in rectal volumes between morning and afternoon treatments were calculated and compared. RESULTS: A total of 1000 CBCT image sets were obtained on 50 patients in the morning and afternoon. The percentage variation of the CBCT rectal volumes over the planning CT scan was 16.57% in the AM group and 24.35% in the PM group. CONCLUSION: The percentage change in rectal volume was significantly lesser in AM group compared to PM group and therefore morning treatments may result in dose distribution that is close to the intended dose distribution. IMPLICATIONS FOR PRACTICE: In prostate cancer radiotherapy our study suggests that a simple technique of changing the time of treatment from afternoon to morning can help to reduce the rectal volume.

First Measurement of the Michel Parameter ξ

We report the first measurement of the Michel parameter ξ^{'} in the τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ} decay with a new method proposed just recently. The measurement is based on the reconstruction of the τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ} events with subsequent muon decay in flight in the Belle central drift chamber. The analyzed data sample of 988 fb^{-1} collected by the Belle detector corresponds to approximately 912×10^{6} τ^{+}τ^{-} pairs. We measure ξ^{'}=0.22±0.94(stat)±0.42(syst), which is in agreement with the standard model prediction of ξ^{'}=1. Statistical uncertainty dominates in this study, being a limiting factor, while systematic uncertainty is well under control. Our analysis proved the practicability of this promising method and its prospects for further precise measurement in future experiments.

Search for the Lepton Flavor Violating Decays B

We present a search for the lepton flavor violating decays B^{+}→K^{+}τ^{±}ℓ^{∓}, with ℓ=(e,µ), using the full data sample of 772×10^{6} BB[over ¯] pairs recorded by the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We use events in which one B meson is fully reconstructed in a hadronic decay mode. We find no evidence for B^{±}→K^{±}τℓ decays and set upper limits on their branching fractions at the 90% confidence level in the (1-3)×10^{-5} range. The obtained limits are the world's best results.

First Measurement of the B

We study B^{+}→π^{+}π^{0}π^{0} using 711 fb^{-1} of data collected at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We measure an inclusive branching fraction of (19.0±1.5±1.4)×10^{-6} and an inclusive CP asymmetry of (9.2±6.8±0.7)%, where the first uncertainties are statistical and the second are systematic, and a B^{+}→ρ(770)^{+}π^{0} branching fraction of (11.2±1.1±0.9_{-1.6}^{+0.8})×10^{-6}, where the third uncertainty is due to possible interference with B^{+}→ρ(1450)^{+}π^{0}. We present the first observation of a structure around 1 GeV/c^{2} in the π^{0}π^{0} mass spectrum, with a significance of 6.4σ, and measure a branching fraction to be (6.9±0.9±0.6)×10^{-6}. We also report a measurement of local CP asymmetry in this structure.

First Observation of Λπ

Using the data sample of 980 fb^{-1} collected with the Belle detector operating at the KEKB asymmetric-energy e^{+}e^{-} collider, we present the results of an investigation of the Λπ^{+} and Λπ^{-} invariant mass distributions looking for substructure in the decay Λ_{c}^{+}→Λπ^{+}π^{+}π^{-}. We find a significant signal in each mass distribution. When interpreted as resonances, we find for the Λπ^{+} (Λπ^{-}) combination a mass of 1434.3±0.6(stat)±0.9(syst) MeV/c^{2} [1438.5±0.9(stat)±2.5(syst) MeV/c^{2}], an intrinsic width of 11.5±2.8(stat)±5.3(syst) MeV/c^{2} [33.0±7.5(stat)±23.6(syst) MeV/c^{2}] with a significance of 7.5σ (6.2σ). As these two signals are very close to the K[over ¯]N threshold, we also investigate the possibility of a K[over ¯]N cusp, and find that we cannot discriminate between these two interpretations due to the limited size of the data sample.

Measurement of the Λ_{c}

An absolute measurement of the Λ_{c}^{+} lifetime is reported using Λ_{c}^{+}→pK^{-}π^{+} decays in events reconstructed from data collected by the Belle II experiment at the SuperKEKB asymmetric-energy electron-positron collider. The total integrated luminosity of the data sample, which was collected at center-of-mass energies at or near the ϒ(4S) resonance, is 207.2 fb^{-1}. The result, τ(Λ_{c}^{+})=203.20±0.89±0.77 fs, where the first uncertainty is statistical and the second systematic, is the most precise measurement to date and is consistent with previous determinations.

Search for a Dark Photon and an Invisible Dark Higgs Boson in µ

The dark photon A^{'} and the dark Higgs boson h^{'} are hypothetical particles predicted in many dark sector models. We search for the simultaneous production of A^{'} and h^{'} in the dark Higgsstrahlung process e^{+}e^{-}→A^{'}h^{'} with A^{'}→µ^{+}µ^{-} and h^{'} invisible in electron-positron collisions at a center-of-mass energy of 10.58 GeV in data collected by the Belle II experiment in 2019. With an integrated luminosity of 8.34 fb^{-1}, we observe no evidence for signal. We obtain exclusion limits at 90% Bayesian credibility in the range of 1.7-5.0 fb on the cross section and in the range of 1.7×10^{-8}-200×10^{-8} on the effective coupling ϵ^{2}×α_{D} for the A^{'} mass in the range of 4.0 GeV/c^{2}

Combatting emerging infectious diseases from Nipah to COVID-19 in Kerala, India.

BACKGROUND: The state of Kerala, India, has experienced several unprecedented events in the past few years. The current study was an attempt to explore perceptions of stakeholders on how the decentralised system helped during the Nipah virus (NiV) outbreaks and COVID-19 pandemic in Kerala. METHODS: This study used a qualitative descriptive approach built on the advocacy paradigm. The stakeholders who were involved in decision-making and the representatives of local self-government who had real-time experience and had handled the challenges were identified using purposive sampling. Seven key informant interviews (KIIs) and nine in-depth interviews (IDIs) were conducted. RESULTS: Findings indicate that decentralisation had enabled the state to effectively deal with the outbreaks and the pandemic. The survey revealed four major themes: decision-making, engagement level, people-centric action, and difficulties. Two to four categories have emerged for each theme. CONCLUSION: The study results highlight the importance of human resources and service delivery as balancing factors during public health emergencies in any developing nation with limited resources. Given that very few nations have the healthcare infrastructure and resources necessary to cater to the healthcare needs of the whole population, decentralisation should be reinforced.

CONTEXTE: L'État du Kérala, Inde, a connu plusieurs évènements sans précèdent au cours des dernières années. Cette étude a cherché à analyser l'opinion des parties prenantes quant à l'aide apportée par le système décentralisé pendant les épidémies de virus Nipah (NiV) et la pandémie de COVID-19 au Kérala. MÉTHODES: Cette étude a eu recours à une méthode descriptive qualitative construite à partir du paradigme de mobilisation. Les parties prenantes impliquées dans la prise de décisions et les représentants des administrations locales autonomes, forts de leur expérience en temps réel et de leur expérience de gestion des défis, ont été identifiés par échantillonnage dirigé. Sept entretiens avec des informateurs clés (KII) et neuf entretiens approfondis (IDI) ont été réalisés. RÉSULTATS: Les résultats indiquent que la décentralisation a permis à l'État de gérer les épidémies et la pandémie de manière efficace. L'enquête a mis en évidence quatre thèmes majeurs : prise de décisions, niveau d'engagement, action centrée sur les personnes et difficultés. Chaque thème a pu être divisé en deux à quatre catégories. CONCLUSION: Les résultats de l'étude soulignent l'importance des ressources humaines et de la fourniture de services en tant que facteurs d'équilibre en période d'urgence de santé publique dans tous les pays en développement dotés de ressources limitées. Puisque très peu de pays disposent des infrastructures de santé et des ressources nécessaires pour répondre aux besoins sanitaires de l'ensemble de la population, la décentralisation devrait être renforcée.

Lipid-droplet associated mitochondria promote fatty-acid oxidation through a distinct bioenergetic pattern in male Wistar rats.

Mitochondria empower the liver to regulate lipid homeostasis by enabling fatty acid oxidation during starvation and lipogenesis during nutrient-rich conditions. It is unknown if mitochondria can seamlessly regulate these two distinct processes or if two discrete populations of mitochondria achieve these two functions in the liver. For the first time in the liver, we report the isolation of two distinct populations of mitochondria from male Wistar rats on an ad-libitum diet: cytoplasmic mitochondria and lipid droplet-associated mitochondria. Our studies show that while lipid droplet mitochondria exhibit higher fatty acid oxidation and are marked by enhanced levels of pACC2, MFN2, and CPT1 activity, cytoplasmic mitochondria are associated with higher respiration capacity. Notably, lipid droplet-associated mitochondria isolated from a non-alcoholic fatty liver disease (NAFLD) rat model are compromised for fatty acid oxidation. We demonstrate the importance of functional segregation of mitochondria as any aberration in lipid droplet-associated mitochondria may lead to NAFLD.

Evidence of a New Excited Charmed Baryon Decaying to Σ_{c}(2455)

We present the study of B[over ¯]^{0}→Σ_{c}(2455)^{0,++}π^{±}p[over ¯] decays based on 772×10^{6} BB[over ¯] events collected with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The Σ_{c}(2455)^{0,++} candidates are reconstructed via their decay to Λ_{c}^{+}π^{∓} and Λ_{c}^{+} decays to pK^{-}π^{+}, pK_{S}^{0}, and Λπ^{+} final states. The corresponding branching fractions are measured to be B(B[over ¯]^{0}→Σ_{c}(2455)^{0}π^{+}p[over ¯])=(1.09±0.06±0.07)×10^{-4} and B(B[over ¯]^{0}→Σ_{c}(2455)^{++}π^{-}p[over ¯])=(1.84±0.11±0.12)×10^{-4}, which are consistent with the world average values with improved precision. A new structure is found in the M_{Σ_{c}(2455)^{0,++}π^{±}} spectrum with a significance of 4.2σ including systematic uncertainty. The structure is possibly an excited Λ_{c}^{+} and is tentatively named Λ_{c}(2910)^{+}. Its mass and width are measured to be (2913.8±5.6±3.8) MeV/c^{2} and (51.8±20.0±18.8) MeV, respectively. The products of branching fractions for the Λ_{c}(2910)^{+} are measured to be B(B[over ¯]^{0}→Λ_{c}(2910)^{+}p[over ¯])×B(Λ_{c}(2910)^{+}→Σ_{c}(2455)^{0}π^{+})=(9.5±3.6±1.6)×10^{-6} and B(B[over ¯]^{0}→Λ_{c}(2910)^{+}p[over ¯])×B(Λ_{c}(2910)^{+}→Σ_{c}(2455)^{++}π^{-})=(1.24±0.35±0.10)×10^{-5}. Here, the first and second uncertainties are statistical and systematic, respectively.

Dysregulation of neuroprotective astrocytes, a spectrum of microglial activation states, and altered hippocampal neurogenesis are revealed by single-cell RNA sequencing in prion disease.

Prion diseases are neurodegenerative disorders with long asymptomatic incubation periods, followed by a rapid progression of cognitive and functional decline culminating in death. The complexity of intercellular interactions in the brain is challenging to unravel and the basis of disease pathobiology remains poorly understood. In this study, we employed single cell RNA sequencing (scRNAseq) to produce an atlas of 147,536 single cell transcriptomes from cortex and hippocampus of mice infected with prions and showing clinical signs. We identified transcriptionally distinct populations and sub-populations of all the major brain cell-types. Disease-related transcription was highly specific to not only overarching cell-types, but also to sub-populations of glia and neurons. Most striking was an apparent decrease in relative frequency of astrocytes expressing genes that are required for brain homeostasis such as lipid synthesis, glutamate clearance, synaptic modulation and regulation of blood flow. Additionally, we described a spectrum of microglial activation states that suggest delineation of phagocytic and neuroinflammatory functions in different cell subsets. Differential responses of immature and mature neuron populations were also observed, alongside abnormal hippocampal neurogenesis. Our scRNAseq library provides a new layer of knowledge on single cell gene expression in prion disease, and is a basis for a more detailed understanding of cellular interplay that leads to neurodegeneration.

Spermidine/Spermine N1-Acetyltransferase 1 (SAT1)-A Potential Gene Target for Selective Sensitization of Glioblastoma Cells Using an Ionizable Lipid Nanoparticle to Deliver siRNA.

Spermidine/spermine N1-acetyltransferase 1 (SAT1) responsible for cell polyamine catabolism is overexpressed in glioblastoma multiforme (GB). Its role in tumor survival and promoting resistance towards radiation therapy has made it an interesting target for therapy. In this study, we prepared a lipid nanoparticle-based siRNA delivery system (LNP-siSAT1) to selectively knockdown (KD) SAT1 enzyme in a human glioblastoma cell line. The LNP-siSAT1 containing ionizable DODAP lipid was prepared following a microfluidics mixing method and the resulting nanoparticles had a hydrodynamic size of around 80 nm and a neutral surface charge. The LNP-siSAT1 effectively knocked down the SAT1 expression in U251, LN229, and 42MGBA GB cells, and other brain-relevant endothelial (hCMEC/D3), astrocyte (HA) and macrophage (ANA-1) cells at the mRNA and protein levels. SAT1 KD in U251 cells resulted in a 40% loss in cell viability. Furthermore, SAT1 KD in U251, LN229 and 42MGBA cells sensitized them towards radiation and chemotherapy treatments. In contrast, despite similar SAT1 KD in other brain-relevant cells no significant effect on cytotoxic response, either alone or in combination, was observed. A major roadblock for brain therapeutics is their ability to cross the highly restrictive blood-brain barrier (BBB) presented by the brain microcapillary endothelial cells. Here, we used the BBB circumventing approach to enhance the delivery of LNP-siSAT1 across a BBB cell culture model. A cadherin binding peptide (ADTC5) was used to transiently open the BBB tight junctions to promote paracellular diffusion of LNP-siSAT1. These results suggest LNP-siSAT1 may provide a safe and effective method for reducing SAT1 and sensitizing GB cells to radiation and chemotherapeutic agents.