Modulation and Determination of the Status of Inflammasomes in Leishmania-Infected Macrophages.

Leishmania, an intra-macrophage kinetoplastid parasite, modulates a vast array of defensive mechanisms of the host macrophages to create a comfortable environment for their survival. When the host encounters intracellular pathogens, a multimeric protein complex called NLRP3 inflammasome gets turned on, leading to caspase-1 activation-mediated maturation of IL-1ß from its pro-form. However, Leishmania often manages to neutralize inflammasome activation by manipulating negative regulatory molecules of the host itself. Exhaustion of NLRP3 and pro-IL-1ß result from decreased NF-κB activity in infection, which was attributed to increased expression of A20, a negative regulator of NF-κB signalling. Moreover, reactive oxygen species, another key requirement for inflammasome activation, are inhibited by mitochondrial uncoupling protein 2 (UCP2) which is upregulated by Leishmania. Inflammasome activation is a complex event and procedures involved in monitoring inflammasome activation need to be accurate and error-free. In this chapter, we summarize the protocol that includes various experimental procedures required for the determination of the status of inflammasomes in Leishmania-infected macrophages.

Microglial cGAS deletion protects against amyloid-ß induced Alzheimer's disease pathogenesis.

Innate immune activation plays a vital role in the development of Alzheimer's disease (AD) and related dementias (ADRD). Among which, the DNA sensing cyclic GMP-AMP synthase (cGAS)- STING pathway has been implicated in diverse aspects of AD progression. In the current study, we showed that the cGAS-STING signaling was up-regulated in AD and this elevation was mainly contributed by the microglial population other than non-microglial cell types in the brain. By establishing an inducible, microglia-specific cGAS knockout mouse model in 5xFAD background, we found that deleting microglial cGAS at the onset of amyloid-ß (Aß) pathology significantly limited plaque formation, and protected mice from Aß-induced cognitive impairment. Mechanistically, we found cGAS was necessary for plaque-associated microglial enrichment potentially driven by IRF8, and was indispensable for the development of disease-associated microglia (DAM) phenotype. Meanwhile, the loss of microglial cGAS reduced the levels of dystrophic neurites which led to preserved synaptic integrity and neuronal function. Our study provides new insights in understanding the effects of innate immune in AD via a cell-type specific manner, and lays the foundation for potential targeted intervention of the microglial cGAS-STING pathway toward the improvement of AD.

Adult-Onset CNS Sulfatide Deficiency Causes Sex-Dependent Metabolic Disruption in Aging.

The interconnection between obesity and central nervous system (CNS) neurological dysfunction has been widely appreciated. Accumulating evidence demonstrates that obesity is a risk factor for CNS neuroinflammation and cognitive impairment. However, the extent to which CNS disruption influences peripheral metabolism remains to be elucidated. We previously reported that myelin-enriched sulfatide loss leads to CNS neuroinflammation and cognitive decline. In this study, we further investigated the impact of CNS sulfatide deficiency on peripheral metabolism while considering sex- and age-specific effects. We found that female sulfatide-deficient mice gained significantly more body weight, exhibited higher basal glucose levels, and were glucose-intolerant during glucose-tolerance test (GTT) compared to age-matched controls under a normal diet, whereas male sulfatide-deficient mice only displayed glucose intolerance at a much older age compared to female sulfatide-deficient mice. Mechanistically, we found that increased body weight was associated with increased food intake and elevated neuroinflammation, especially in the hypothalamus, in a sex-specific manner. Our results suggest that CNS sulfatide deficiency leads to sex-specific alterations in energy homeostasis via dysregulated hypothalamic control of food intake.

Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer's disease.

BACKGROUND: Despite being a brain disorder, Alzheimer's disease (AD) is often accompanied by peripheral organ dysregulations (e.g., loss of bladder control in late-stage AD), which highly rely on spinal cord coordination. However, the causal factor(s) for peripheral organ dysregulation in AD remain elusive. METHODS: The central nervous system (CNS) is enriched in lipids. We applied quantitative shotgun lipidomics to determine lipid profiles of human AD spinal cord tissues. Additionally, a CNS sulfatide (ST)-deficient mouse model was used to study the lipidome, transcriptome and peripheral organ phenotypes of ST loss. RESULTS: We observed marked myelin lipid reduction in the spinal cord of AD subjects versus cognitively normal individuals. Among which, levels of ST, a myelin-enriched lipid class, were strongly and negatively associated with the severity of AD. A CNS myelin-specific ST-deficient mouse model was used to further identify the causes and consequences of spinal cord lipidome changes. Interestingly, ST deficiency led to spinal cord lipidome and transcriptome profiles highly resembling those observed in AD, characterized by decline of multiple myelin-enriched lipid classes and enhanced inflammatory responses, respectively. These changes significantly disrupted spinal cord function and led to substantial enlargement of urinary bladder in ST-deficient mice. CONCLUSIONS: Our study identified CNS ST deficiency as a causal factor for AD-like lipid dysregulation, inflammation response and ultimately the development of bladder disorders. Targeting to maintain ST levels may serve as a promising strategy for the prevention and treatment of AD-related peripheral disorders.

A mechanistic analysis of spontaneous cancer remission phenomenon: identification of genomic basis and effector biomolecules for therapeutic applicability.

Based on the well-documented studies, numerous tumors episodically regress permanently without treatment. Knowing the host tissue-initiated causative factors would offer considerable translational applicability, as a permanent regression process may be therapeutically replicated on patients. For this, we developed a systems biological formulation of the regression process with experimental verification and identified the relevant candidate biomolecules for therapeutic utility. We devised a cellular kinetics-based quantitative model of tumor extinction in terms of the temporal behavior of three main tumor-lysis entities: DNA blockade factor, cytotoxic T-lymphocyte and interleukin-2. As a case study, we analyzed the time-wise biopsy and microarrays of spontaneously regressing melanoma and fibrosarcoma tumors in mammalian/human hosts. We analyzed the differentially expressed genes (DEGs), signaling pathways, and bioinformatics framework of regression. Additionally, prospective biomolecules that could cause complete tumor regression were investigated. The tumor regression process follows a first-order cellular dynamics with a small negative bias, as verified by experimental fibrosarcoma regression; the bias is necessary to eliminate the residual tumor. We identified 176 upregulated and 116 downregulated DEGs, and enrichment analysis showed that the most significant were downregulated cell-division genes: TOP2A-KIF20A-KIF23-CDK1-CCNB1. Moreover, Topoisomerase-IIA inhibition might actuate spontaneous regression, with collateral confirmation provided from survival and genomic analysis of melanoma patients. Candidate molecules such as Dexrazoxane/Mitoxantrone, with interleukin-2 and antitumor lymphocytes, may potentially replicate permanent tumor regression process of melanoma. To conclude, episodic permanent tumor regression is a unique biological reversal process of malignant progression, and signaling pathway understanding, with candidate biomolecules, may plausibly therapeutically replicate the regression process on tumors clinically. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03515-0.

Conjoint hepatobiliary-enterohepatic cycles for amyloid excretion and enhancing its drug-induced clearance: a systems biology approach to Alzheimer's disease.

The liver is the major organ responsible for metabolism of amyloid-beta, the primary toxic misfolded protein responsible for Alzheimer's disease (AD). The present study focuses on the crucial role of liver in AD. We have developed a framework that formulates and integrates two reciprocal transport processes of amyloid, via hepato-biliary and enterohepatic circulations (EHC). Our system analysis approach shows that activating the liver X-receptor (LXR) can reduce amyloid-beta formation by increasing expression of the genes: ATP-binding-cassette-transporter (ABCA1) and Stearoyl-CoA-desaturase (SCD). Besides, activating the pregnane-X-receptor (PXR) can enhance the clearance of amyloid-beta by increasing the expression of the genes: ATP-Binding-Cassette-Superfamily-G-member-2 (ABCG2) and multidrug-resistance protein-1 (MDR1). We also identified receptor-like apical sodium-dependent bile-acid transporter (ASBT) of intestinal enterocyte, showing affinity towards amyloid-beta, suggesting amyloid-beta's possible reuptake from intestinal contents to the systemic circulation through this receptor. Further, we have performed protein-protein interaction to evaluate the binding affinity of amyloid-beta to these receptors. Moreover, we undertook molecular docking and molecular dynamic simulation of some repurposed drugs (rifampicin, 24-hydroxycholesterols, resveratrol, cilostazol) which can target the aforesaid receptors to enhance amyloid-beta's fecal clearance, reduce amyloid-beta formation, and prevent the reuptake of amyloid-beta from intestinal feces. Additionally, network pharmacology and synergism analysis were utilized to validate our hypothesis and identify the drug combinations, respectively. Gene-ontology investigation, network pharmacology, and consolidated pathway analysis validate the alteration of the above-mentioned gene expression profiles. Furthermore, our neuropharmacological synergism study identifies the optimal combination of the repurposed drugs. Finally, our findings on candidate drugs are substantiated by clinical-trial outcomes.Communicated by Ramaswamy H. Sarma.

Neuroprotective Drug Discovery From Phytochemicals and Metabolites for CNS Viral Infection: A Systems Biology Approach With Clinical and Imaging Validation.

Background: Recent studies have reported that pulmo-neurotropic viruses can cause systemic invasion leading to acute respiratory failure and neuroinfection. The tetracycline class of secondary metabolites of microorganisms is effective against several migrating neurotropic viral disorders, as Japanese-Encephalitis (JE), Severe-Acute-Respiratory-Syndrome Coronavirus-2 (SARS-COV2), Human-Immunodeficiency-Virus (HIV), and Simian-Immunodeficiency-Virus (SIV). Another microbial secondary metabolite, cephalosporin, can be used for anti-viral combination therapy. However, a substantial public health debacle is viral resistance to such antibiotics, and, thus, one needs to explore the antiviral efficiency of other secondary metabolites, as phytochemicals. Hence, here, we investigate phytochemicals like podophyllotoxin, chlorogenic acid, naringenin, and quercetin for therapeutic efficiency in neurotropic viral infections. Methods: To investigate the possibility of the afferent neural pathway of migrating virus in man, MRI scanning was performed on human subjects, whereby the connections between cranial nerves and the brain-stem/limbic-region were assessed by fiber-tractography. Moreover, human clinical-trial assessment (n = 140, p = 0.028) was done for formulating a quantitative model of antiviral pharmacological intervention. Furthermore, docking studies were performed to identify the binding affinity of phytochemicals toward antiviral targets as (i) host receptor [Angiotensin-converting Enzyme-2], (ii) main protease of SARS-COV2 virus (iii) NS3-Helicase/Nucleoside triphosphatase of Japanese-encephalitis-virus, and the affinities were compared to standard tetracycline and cephalosporin antibiotics. Then, network pharmacology analysis was utilized to identify the possible mechanism of action of those phytochemicals. Results: Human MRI-tractography analysis showed fiber connectivity, as: (a) Path-1: From the olfactory nerve to the limbic region (2) Path-2: From the peripheral glossopharyngeal nerve and vagus nerves to the midbrain-respiratory-center. Docking studies revealed comparable binding affinity of phytochemicals, tetracycline, and cephalosporin antibiotics toward both (a) virus receptors, (b) host cell receptors where virus-receptor binds. The phytochemicals effectively countered the cytokine storm-induced neuroinflammation, a critical pathogenic pathway. We also found that a systems-biology-based double-hit mathematical bi-exponential model accounts for patient survival-curve under antiviral treatment, thus furnishing a quantitative-clinical framework of secondary metabolite action on virus and host cells. Conclusion: Due to the current viral resistance to antibiotics, we identified novel phytochemicals that can have clinical therapeutic application to neurotropic virus infection. Based on human MRI scanning and clinical-trial analysis, we demarcated the anatomical pathway and systems-biology-based quantitative formulation of the mechanism of antiviral action.

Evaluation of rosmarinic acid against myocardial infarction in maternally separated rats.

Depression and coronary heart diseases are the common comorbid disorder affecting humans globally. The present study evaluated the effectiveness of rosmarinic acid (RA) against myocardial infarction (MI) in comorbid depression induced by maternal separation in rats. Maternal stress is one of the childhood crises that may be a potential risk factor for coronary heart disease in later part of life. As per protocol, 70-80% of pups were separated daily for 3 h between postnatal day 1 (PND1) and postnatal day 21 (PND21). Forced-swim test, sucrose preference test, and electrocardiography were performed during the experiment. Body weight was measured on PND0, PND35, and PND55. Orally rosmarinic acid (25 mg/kg and 50 mg/kg) and fluoxetine (10 mg/kg) was done from PND35 to PND55. On PND53 and PND54, isoproterenol (100 mg/kg, subcutaneously) was administered to induce myocardial infarction. On PND55, blood was collected and animals sacrificed, and plasma corticosterone, brain-derived neurotrophic factor, cardiac biomarkers, interleukine-10, and anti-oxidant parameters were measured. Rosmarinic acid and fluoxetine ameliorated the maternal separation-induced increase in immobility period, anhedonia, body weight, ST elevation, corticosterone, creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). At the same time, both drugs elevated the tissue levels of BDNF, IL-10, glutathione, and superoxide dismutase activity. This study provides the first experimental evidence that maternal stress is an independent risk factor of cardiac abnormalities in rats. Moreover, maternal stress synergistically increases the severity of cardiac abnormalities induced by isoproterenol. Interestingly, fluoxetine and rosmarinic acid effectively ameliorated behavioral anomalies and myocardial infarction in maternally separated rats. Schematic representation of possible molecular mechanism of action of rosmarinic acid against MS-induced myocardial infarction. RA, rosmarinic acid; MS, maternal separation; PND, postnatal days; ISO, isoproterenol; BDNF, brain-derived neurotrophic factor; GSH, glutathione; SOD, superoxide dismutase; IL-10, interleukin-10; MI, myocardial infarction.

Synthesis, bio-physical and anti-leishmanial studies of some novel indolo[3,2-a]phenanthridine derivatives.

Eight indolo[3,2-a]phenanthridine derivatives have been synthesized in a regioselective manner involving intramolecular Heck-type arylation as a key step. The compounds display interesting photophysical proprties and hence evaluated for their ability to interact with ct-DNA. Preliminary biophysical studies via UV and Fluorescence spectrophotometric titration with ct-DNA, and dye displacement studies with well known intercalator ethidium bromide and the groove binder Hoechst 33,258 reveal that the binding mode is probably minor groove binding. The prepared indolophenanthridine derivatives have also been evaluated as anti-leishmanial agents for the first time. MTT-assays for cell cytotoxicity against Leishmania promastigotes and Leishmania amastigotes were studied with the compounds 10b-f, 12-14 for the determination of their IC50 values. Cytotoxicity was determined using a murine RAW 264.7 cell line and human embryonic kidney cell line HEK 293. In L. donovani amastigote assay, compounds 10e, 10f and 12 showed good activity with relatively low cytotoxicity against RAW 264.7, resulting in acceptable selectivity indices. Selectivity index determination indicated compounds to be potent anti-leishmanial agents while 10b, 10c and 14 showed moderate selectivity index. Moreover, cell-cycle analysis of four different compounds 10b, 12, 13 and 14, representative of each group, was performed by FACS as an attempt to understand the mechanism of actions of these different sub-classes of the compounds on Leishmania.

Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer's disease-like neuroinflammation and cognitive impairment.

BACKGROUND: Human genetic association studies point to immune response and lipid metabolism, in addition to amyloid-beta (Aß) and tau, as major pathways in Alzheimer's disease (AD) etiology. Accumulating evidence suggests that chronic neuroinflammation, mainly mediated by microglia and astrocytes, plays a causative role in neurodegeneration in AD. Our group and others have reported early and dramatic losses of brain sulfatide in AD cases and animal models that are mediated by ApoE in an isoform-dependent manner and accelerated by Aß accumulation. To date, it remains unclear if changes in specific brain lipids are sufficient to drive AD-related pathology. METHODS: To study the consequences of CNS sulfatide deficiency and gain insights into the underlying mechanisms, we developed a novel mouse model of adult-onset myelin sulfatide deficiency, i.e., tamoxifen-inducible myelinating glia-specific cerebroside sulfotransferase (CST) conditional knockout mice (CSTfl/fl/Plp1-CreERT), took advantage of constitutive CST knockout mice (CST-/-), and generated CST/ApoE double knockout mice (CST-/-/ApoE-/-), and assessed these mice using a broad range of methodologies including lipidomics, RNA profiling, behavioral testing, PLX3397-mediated microglia depletion, mass spectrometry (MS) imaging, immunofluorescence, electron microscopy, and Western blot. RESULTS: We found that mild central nervous system (CNS) sulfatide losses within myelinating cells are sufficient to activate disease-associated microglia and astrocytes, and to increase the expression of AD risk genes (e.g., Apoe, Trem2, Cd33, and Mmp12), as well as previously established causal regulators of the immune/microglia network in late-onset AD (e.g., Tyrobp, Dock, and Fcerg1), leading to chronic AD-like neuroinflammation and mild cognitive impairment. Notably, neuroinflammation and mild cognitive impairment showed gender differences, being more pronounced in females than males. Subsequent mechanistic studies demonstrated that although CNS sulfatide losses led to ApoE upregulation, genetically-induced myelin sulfatide deficiency led to neuroinflammation independently of ApoE. These results, together with our previous studies (sulfatide deficiency in the context of AD is mediated by ApoE and accelerated by Aß accumulation) placed both Aß and ApoE upstream of sulfatide deficiency-induced neuroinflammation, and suggested a positive feedback loop where sulfatide losses may be amplified by increased ApoE expression. We also demonstrated that CNS sulfatide deficiency-induced astrogliosis and ApoE upregulation are not secondary to microgliosis, and that astrogliosis and microgliosis seem to be driven by activation of STAT3 and PU.1/Spi1 transcription factors, respectively. CONCLUSION: Our results strongly suggest that sulfatide deficiency is an important contributor and driver of neuroinflammation and mild cognitive impairment in AD pathology.

Supplementation of taurine improves ionic homeostasis and mitochondrial function in the rats exhibiting post-traumatic stress disorder-like symptoms.

RATIONALE: Current pharmacotherapy for post-traumatic stress disorder (PTSD) is limited to few antidepressants. Mitochondrial dysfunction is observed in PTSD, along with altered potassium homeostasis. Nutritional supplementation of taurine can improve ionic homeostasis and thereby treat PTSD-like symptoms in rats. AIM: The purpose is to study the pharmacological effect of taurine in stress re-stress-induced PTSD in rats. METHODS: As per protocol, animals were restrained for 2 h then exposed to footshock (FS) (2 mA/10 s) followed by halothane-induced anesthesia. Behavioral assessments such as elevated plus maze (EPM) and Y-maze tests were performed on days 2, 8, and 32 of experimental protocol after re-stress. In addition, daily oral administration of taurine (100, 200, and 300 mg/kg) and paroxetine (PAX) (10 mg/kg) was done from D-8 to D-32 followed by re-stress. The plasma concentration of taurine, corticosterone, and potassium was measured on Day-32 along with mitochondrial function in discrete brain regions. RESULTS: Sub-chronic administration of taurine in high and medium doses significantly ameliorated PTSD-like symptoms such as hyperarousal, anxiety, and improved spatial recognition memory. Taurine in all doses restored the plasma concentration of corticosterone and potassium. SRS-induced alterations in mitochondrial bioenergetics, complex enzyme activities, and reduced mitochondrial membrane potential in different brain regions were ameliorated by taurine. CONCLUSION: Nutritional supplementation of taurine improves potassium ionic homeostasis, mitochondrial function, and attenuated PTSD-like symptoms in SRS subjected rats.

Evaluation of Modulators of cAMP-Response in Terms of Their Impact on Cell Cycle and Mitochondrial Activity of Leishmania donovani.

With the identification of novel cAMP binding effector molecules in Trypanosoma, the role of cAMP in kinetoplastida parasites gained an intriguing breakthrough. Despite earlier demonstrations of the role of cAMP in the survival of Leishmania during macrophage infection, there is essential need to specifically clarify the involvement of cAMP in various cellular processes in the parasite. In this context, we sought to gain a comprehensive understanding of the effect of cAMP analogs and cAMP-cyclic nucleotide phosphodiesterase (PDE) inhibitors on proliferation of log phase parasites. Administration of both hydrolyzable (8-pCPT-cAMP) and nonhydrolyzable analogs (Sp-8-pCPT-cAMPS) of cAMP resulted in a significant decrease of Leishmania proliferation. Among the various PDE inhibitors, etazolate was found to be potently antiproliferative. BrdU cell proliferation and K/N/F-enumeration microscopic study revealed that both cAMP analogs and selective PDE inhibitors resulted in significant cell cycle arrest at G1 phase with reduced S-phase population. Furthermore, careful examination of the flagellar motility patterns revealed significantly reduced coordinated forward flagellar movement of the promastigotes with a concomitant decrease in cellular ATP levels. Alongside, 8-pCPT-cAMP and PDE inhibitors etazolate and trequinsin showed marked reduction in mitochondrial membrane potential. Treatment of etazolate at subcytotoxic concentration to infected macrophages significantly reduced parasite burden, and administration of etazolate to Leishmania-infected BALB/c mice showed reduced liver and spleen parasite burden. Collectively, these results imply involvement of cAMP in various crucial processes paving the avenue for developing potent antileishmanial agent.

Mobilization-based transplantation of young-donor hematopoietic stem cells extends lifespan in mice.

Mammalian aging is associated with reduced tissue regeneration and loss of physiological integrity. With age, stem cells diminish in their ability to regenerate adult tissues, likely contributing to age-related morbidity. Thus, we replaced aged hematopoietic stem cells (HSCs) with young-donor HSCs using a novel mobilization-enabled hematopoietic stem cell transplantation (HSCT) technology as an alternative to the highly toxic conditioning regimens used in conventional HSCT. Using this approach, we are the first to report an increase in median lifespan (12%) and a decrease in overall mortality hazard (HR: 0.42, CI: 0.273-0.638) in aged mice following transplantation of young-donor HSCs. The increase in longevity was accompanied by reductions of frailty measures and increases in food intake and body weight of aged recipients. Young-donor HSCs not only preserved youthful function within the aged bone marrow stroma, but also at least partially ameliorated dysfunctional hematopoietic phenotypes of aged recipients. This compelling evidence that mammalian health and lifespan can be extended through stem cell therapy adds a new category to the very limited list of successful anti-aging/life-extending interventions. Our findings have implications for further development of stem cell therapies for increasing health and lifespan.

Non-toxic HSC Transplantation-Based Macrophage/Microglia-Mediated GDNF Delivery for Parkinson's Disease.

Glial cell-line-derived neurotrophic factor (GDNF) is a potent neuroprotective agent in cellular and animal models of Parkinson's disease (PD). However, CNS delivery of GDNF in clinical trials has proven challenging due to blood-brain barrier (BBB) impermeability, poor diffusion within brain tissue, and large brain size. We report that using non-toxic mobilization-enabled preconditioning, hematopoietic stem cell (HSC) transplantation-based macrophage-mediated gene delivery may provide a solution to overcome these obstacles. Syngeneic bone marrow HSCs were transduced ex vivo with a lentiviral vector expressing macrophage promoter-driven GDNF and transplanted into 14-week-old MitoPark mice exhibiting PD-like impairments. Transplant preconditioning with granulocyte colony-stimulating factor (G-CSF) and AMD3100 was used to vacate bone marrow stem cell niches. Chimerism reached ∼80% after seven transplantation cycles. Transgene-expressing macrophages infiltrated degenerating CNS regions of MitoPark mice (not wild-type littermate controls), resulting in increased GDNF levels in the midbrain. Macrophage GDNF delivery not only markedly improved motor and non-motor dysfunction, but also dramatically mitigated the loss of dopaminergic neurons in both substantia nigra and the ventral tegmental area and preserved axonal terminals in the striatum. Striatal dopamine levels were almost completely restored. Our data support further development of mobilization-enabled HSC transplantation (HSCT)-based macrophage-mediated GDNF gene delivery as a disease-modifying therapy for PD.

Electromagnetically induced transparency with quantum interferometry.

We have shown that electromagnetically induced transparency can be achieved by control-probe interferometry using two delayed phase-locked ultrashort pulses. Two vibrational wavepackets on the excited state, excited by two delayed phase-locked ultrashort pulses, interfere constructively or destructively leading to enhancement or suppression of absorption to a selective set of vibrational levels. Depending on the phase difference and the delay between the pulses with same carrier frequency, one can design different transparency windows between absorption peaks at consecutive even(odd) vibrational levels by eliminating absorption at odd(even) vibrational levels. We have shown that by switching the phase difference of two delayed femtosecond pulses, one can switch to complete elimination of absorption from enhanced absorption to a particular set of vibrational levels in the excited state. Thus, switching of transparency through window between odd vibrational levels to that between even vibrational levels is possible. By properly choosing the temporal width and the carrier frequency of the pulses, lossless transmission of complete or bands of frequencies of the pulses can be achieved through these transparency windows. Hence, designing of single- or multi-mode transparency windows in NaH molecule is feasible by control-probe quantum interferometry.