Probiotics and the envisaged role in treating human infertility

Abstract Background Considerable attention is being directed nowadays towards using probiotics as an alternative therapy in treating several human diseases including gastrointestinal tract diseases especially colorectal cancers, cardiovascular diseases, hyperlipidemia, and blood pressure cases. However, infertility as affected by the microbiome and the probable role of probiotics in alleviating infertility problems did not receive the deserved attention, especially in IVF patients with male or female factors. Main body In this review, we tried to draw the attention of researchers in the medical settings to the importance of the forthcoming role of probiotics use in elucidating the role of the microbiome in infertile patients. The hope is to attain the best performance of both male and female reproductive systems and to shed some light on infertility problems. Conclusion More in vivo experiments are still needed to address many aspects of probiotics like proper administration, exact functional strains, required dose, application method, duration of treatment, and combination with antibiotics before considering probiotics as an alternative treatment.

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The Extracellular Small Leucine-Rich Proteoglycan Biglycan Is a Key Player in Gastric Cancer Aggressiveness

Cancers ◽

10.3390/cancers13061330 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1330

Author(s):

Filipe Pinto ◽

Liliana Santos-Ferreira ◽

Marta T. Pinto ◽

Catarina Gomes ◽

Celso A. Reis

Keyword(s):

Clinical Value ◽

Knock Out ◽

Angiogenic Potential ◽

In Vivo Experiments ◽

Cancer Aggressiveness ◽

Advanced Stages ◽

Oncogenic Gene

Biglycan (BGN gene), an extracellular proteoglycan, has been described to be associated with cancer aggressiveness. The purpose of this study was to clarify the clinical value of biglycan as a biomarker in multiple independent GC cohorts and determine the in vitro and in vivo role of biglycan in GC malignant features. We found that BGN is commonly over-expressed in all analyzed cohorts, being associated with disease relapse and poor prognosis in patients with advanced stages of disease. In vitro and in vivo experiments demonstrated that biglycan knock-out GC cells display major phenotypic changes with a lower cell survival, migration, and angiogenic potential when compared with biglycan expressing cells. Biglycan KO GC cells present increased levels of PARP1 and caspase-3 cleavage and a decreased expression of mesenchymal markers. Importantly, biglycan deficient GC cells that were supplemented with exogenous biglycan were able to restore biological features, such as survival, clonogenic and migratory capacities. Our in vitro and in vivo findings were validated in human GC samples, where BGN expression was associated with several oncogenic gene signatures that were associated with apoptosis, cell migration, invasion, and angiogenesis. This study provided new insights on biglycan role in GC that should be taken in consideration as a key cellular regulator with major impact in tumor progression and patients’ clinical outcome.

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Paradoxical effect of salbutamol in a model of acute organophosphates intoxication in guinea pigs: role of substance P release

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00253.2005 ◽

2007 ◽

Vol 292 (4) ◽

pp. L915-L923 ◽

Cited By ~ 10

Author(s):

Jaime Chávez ◽

Patricia Segura ◽

Mario H. Vargas ◽

José Luis Arreola ◽

Edgar Flores-Soto ◽

...

Keyword(s):

Substance P ◽

Guinea Pigs ◽

Smooth Muscle Contraction ◽

In Vivo Experiments ◽

Intracellular Ca ◽

Neurokinin 1 ◽

Substance P Release

Organophosphates induce bronchoobstruction in guinea pigs, and salbutamol only transiently reverses this effect, suggesting that it triggers additional obstructive mechanisms. To further explore this phenomenon, in vivo (barometric plethysmography) and in vitro (organ baths, including ACh and substance P concentration measurement by HPLC and immunoassay, respectively; intracellular Ca2+ measurement in single myocytes) experiments were performed. In in vivo experiments, parathion caused a progressive bronchoobstruction until a plateau was reached. Administration of salbutamol during this plateau decreased bronchoobstruction up to 22% in the first 5 min, but thereafter airway obstruction rose again as to reach the same intensity as before salbutamol. Aminophylline caused a sustained decrement (71%) of the parathion-induced bronchoobstruction. In in vitro studies, paraoxon produced a sustained contraction of tracheal rings, which was fully blocked by atropine but not by TTX, ω-conotoxin (CTX), or epithelium removal. During the paraoxon-induced contraction, salbutamol caused a temporary relaxation of ∼50%, followed by a partial recontraction. This paradoxical recontraction was avoided by the M2- or neurokinin-1 (NK1)-receptor antagonists (methoctramine or AF-DX 116, and L-732138, respectively), accompanied by a long-lasting relaxation. Forskolin caused full relaxation of the paraoxon response. Substance P and, to a lesser extent, ACh released from tracheal rings during 60-min incubation with paraoxon or physostigmine, respectively, were significantly increased when salbutamol was administered in the second half of this period. In myocytes, paraoxon did not produce any change in the intracellular Ca2+ basal levels. Our results suggested that: 1) organophosphates caused smooth muscle contraction by accumulation of ACh released through a TTX- and CTX-resistant mechanism; 2) during such contraction, salbutamol relaxation is functionally antagonized by the stimulation of M2 receptors; and 3) after this transient salbutamol-induced relaxation, a paradoxical contraction ensues due to the subsequent release of substance P.

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Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle

Nature Communications ◽

10.1038/s41467-021-21063-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Maximilian M. Biebl ◽

Abraham Lopez ◽

Alexandra Rehn ◽

Lee Freiburger ◽

Jannis Lawatscheck ◽

...

Keyword(s):

Proximal Region ◽

Tryptophan Residue ◽

Structural Elements ◽

Physiological Importance ◽

In Vivo Experiments ◽

Cellular Context ◽

Catalytic Loop ◽

Hsp90 Chaperone

AbstractThe co-chaperone p23 is a central part of the Hsp90 machinery. It stabilizes the closed conformation of Hsp90, inhibits its ATPase and is important for client maturation. Yet, how this is achieved has remained enigmatic. Here, we show that a tryptophan residue in the proximal region of the tail decelerates the ATPase by allosterically switching the conformation of the catalytic loop in Hsp90. We further show by NMR spectroscopy that the tail interacts with the Hsp90 client binding site via a conserved helix. This helical motif in the p23 tail also binds to the client protein glucocorticoid receptor (GR) in the free and Hsp90-bound form. In vivo experiments confirm the physiological importance of ATPase modulation and the role of the evolutionary conserved helical motif for GR activation in the cellular context.

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Toward heterogeneity in feedforward network with synaptic delays based on FitzHugh–Nagumo model

International Journal of Modern Physics B ◽

10.1142/s0217979217502745 ◽

2018 ◽

Vol 32 (01) ◽

pp. 1750274 ◽

Cited By ~ 4

Author(s):

Ying-Mei Qin ◽

Cong Men ◽

Jia Zhao ◽

Chun-Xiao Han ◽

Yan-Qiu Che

Keyword(s):

Neuronal Excitability ◽

Temporal Coding ◽

Feedforward Network ◽

Firing Patterns ◽

In Vivo Experiments ◽

Connection Probability ◽

Rate Coding

We focus on the role of heterogeneity on the propagation of firing patterns in feedforward network (FFN). Effects of heterogeneities both in parameters of neuronal excitability and synaptic delays are investigated systematically. Neuronal heterogeneity is found to modulate firing rates and spiking regularity by changing the excitability of the network. Synaptic delays are strongly related with desynchronized and synchronized firing patterns of the FFN, which indicate that synaptic delays may play a significant role in bridging rate coding and temporal coding. Furthermore, quasi-coherence resonance (quasi-CR) phenomenon is observed in the parameter domain of connection probability and delay-heterogeneity. All these phenomena above enable a detailed characterization of neuronal heterogeneity in FFN, which may play an indispensable role in reproducing the important properties of in vivo experiments.

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Metformin Sensitizes Osteosarcoma Cells to Chemotherapy Through IGF-1R/miR-610/FEN1 Pathway

10.21203/rs.3.rs-147084/v1 ◽

2021 ◽

Author(s):

Suwei Dong ◽

Yanbin Xiao ◽

Ziqiang Zhu ◽

Xiang Ma ◽

Zhuohui Peng ◽

...

Keyword(s):

Underlying Mechanism ◽

Cytotoxic Agents ◽

Luciferase Reporter ◽

Osteosarcoma Cell ◽

Metformin Treatment ◽

Normal Tissues ◽

Qrt Pcr ◽

In Vivo Experiments

Abstract Background: Due to constitutive or acquired non-sensitive to cytotoxic agents, the prognosis of osteosarcoma remains unfavorable. It’s has been proved that metformin could enhance the chemosensitivity of cancer cells to anticancer drugs. A novel finding states that IGF-1R involves in cancer chemoresistance, However, whether IGF-1R play a role in metformin-induced osteosarcoma chemosensitivity is incompletely understood. Hence, the current study aimed to elucidate the role of metformin in OS cell chemosensitivity modulation to identify the underlying mechanism of metformin regulating the IGF-1R/miR-610/FEN1 signaling.Methods: Immunohistochemistry and qRT-PCR were used to evaluate the expression pattern of IGF-1R, miR-610 and FEN1 in osteosarcoma and paired normal tissues. Western blot and qRT-PCR were performed to determine changes in expression of key molecules in the IGF-1R/miR-610/FEN1 signaling pathway after various treatments. The direct modulation between miR-610 and FEN1 was monitored by luciferase reporter assay. Osteosarcoma cell sensitivity to chemotherapy was detected by MTS assay. In vivo experiments were conducted to further verify the role of the metformin in the chemosensitivity modulation of OS cells to ADM.Results: We found that IGF-1R, miR-610 and FEN1 were abberently expressed in osteosarcoma, and participated in apoptosis modulation (p < 0.05). We found that this effect was abated by metformin treatment. Luciferase reporter assays confirmed that FEN1 is a direct target of miR-610. Moreover, we observed that metformin treatment decreased IGF-1R and FEN1, but elevated miR-610 expression. Metformin sensitized OS cells to cytotoxic agents, while overexpression of FEN1 compromised the sensitizing effects of metformin partly. Furthermore, metformin was observed to enforce the ADM treatment effect in nude mice xenograft models.Conclusions: Overall, metformin enhanced the sensitivity of OS cells to cytotoxic agents via the IGF-1R/miR-610/FEN1 signaling axis, highlighting the capacity of metformin as an adjunct to the chemotherapy of OS.

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MiR-125b-5p Inhibited The Progression of Hepatoblastoma As A Shared miRNA of The lncRNA NEAT1 and YES1

10.21203/rs.3.rs-49445/v1 ◽

2020 ◽

Author(s):

Zhu Jin ◽

Yutong Chen ◽

Yuchen Mao ◽

Mingjuan Gao ◽

Zebing Zheng ◽

...

Keyword(s):

Clinicopathological Characteristics ◽

Luciferase Reporter ◽

Tumor Growth Inhibition ◽

Invasion And Migration ◽

In Vivo Experiments ◽

Reporter Assays ◽

And Migration ◽

Relationship Of

Abstract Background: microRNAs have been studied widely in hepatoblastoma. However, the role of miR-125b-5p and its relationship with the lncRNA sNEAT1 and YES1 in hepatoblastoma have not been reported previously. We aimed to reveal the role of NEAT1/miR-125b-5p/YES1 in the progression of hepatoblastoma.Methods: We collected tumor tissues and their adjacent tissues from 12 hepatoblastoma patients. qRT-PCR was applied to detect the expression of miR-125b-5p, and the relationship of miR-125b-5p with clinicopathological characteristics was analyzed. Dual luciferase reporter assays and RNA pull down assays were used to identify the relationships among NEAT1, miR-125b-5p and YES1. CCK8, Transwell assays and wound healing assays were used to examine cell viability, invasion and migration. In vivo experiments were also applied to detect the effect of miR-125b-5p on hepatoblastoma.Results: miR-125b-5p was significantly downregulated in hepatoblastoma tissue and cells. The higher the PRETEXT grade, the lower the miR-125b-5p level. NEAT1 could bind to miR-125b-5p and inhibit its expression. miR-125b-5p could target YES1 and inhibit its expression. Overexpression of miR-125b-5p decreased the proliferation, invasion, and migratory ability of hepatoblastoma cells. YES1 could rescue the above effects. At the same time, overexpression of miR-125b-5p resulted in decreased YES1 and tumor growth inhibition in vivo.Conclusion: miR-125b-5p acted as a shared miRNA of NEAT1 and YES1 in hepatoblastoma. Overexpression of miR-125b-5p could target YES1 and inhibit its expression, therefore inhibiting the progression of hepatoblastoma.

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A role for the EphA family in the topographic targeting of vomeronasal axons

Development ◽

10.1242/dev.128.6.895 ◽

2001 ◽

Vol 128 (6) ◽

pp. 895-906

Author(s):

B. Knoll ◽

K. Zarbalis ◽

W. Wurst ◽

U. Drescher

Keyword(s):

Tyrosine Kinases ◽

Expression Patterns ◽

Eph Receptors ◽

Accessory Olfactory Bulb ◽

In Vivo Experiments ◽

Receptor Concentration ◽

High Ligand

We have investigated the role of the Eph family of receptor tyrosine kinases and their ligands in the establishment of the vomeronasal projection in the mouse. Our data show intriguing differential expression patterns of ephrin-A5 on vomeronasal axons and of EphA6 in the accessory olfactory bulb (AOB), such that axons with high ligand concentration project onto regions of the AOB with high receptor concentration and vice versa. These data suggest a mechanism for development of this projection that is the opposite of the repellent interaction between Eph receptors and ligands observed in other systems. In support of this idea, when given the choice of whether to grow on lanes containing EphA-F(c)/laminin or F(c)/laminin protein (in the stripe assay), vomeronasal axons prefer to grow on EphA-F(c)/laminin. Analysis of ephrin-A5 mutant mice revealed a disturbance of the topographic targeting of vomeronasal axons to the AOB. In summary, these data, which are derived from in vitro and in vivo experiments, indicate an important role of the EphA family in setting up the vomeronasal projection.

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Transthyretin (TTR) Suppressed Tumor Progression in Non-Small Cell Lung Cancer by Inactivating MAPK/ERK Pathway

10.21203/rs.3.rs-38779/v1 ◽

2020 ◽

Author(s):

Dong-bin Wang ◽

Xuan Li ◽

Xi-ke Lu ◽

Zhong-yi Sun ◽

Xun Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Carcinoma ◽

Clinical Care ◽

Small Cell ◽

Signal Pathways ◽

Small Cell Lung ◽

Cell Lung Carcinoma ◽

In Vivo Experiments

Abstract Background: Lung cancer is a leading cause of cancer death around the world, while the Transthyretin (TTR) is a specific biomarkers for clinical diagnosis. However, its role in lung cancer remains to be unknown. Methods: In the present study, we made attempt to investigate effect of abnormal expression of TTR on Non-small-cell lung carcinoma (NSCLC) by overexpression or knockdown of TTR.To further investigate the mechanisms underlying the potential role of TTR in NSCLC, we searched and verified several signal pathways . In vivo experiments, to verify the effect of TTR overexpression on tumors.Results: We finded that up-regulated TTR obviously suppressed cell proliferation, migration, invasion and increased apoptosis.Significant suppression of phosphor-MAPK/ERK was observed in TTR-treated NSCLC cells, implying that TTR was important for cellular progress by regulating MAPK/ERK signaling pathway. In vivo experiment, overexpression of TTR promoted cell apoptosis and inhibited tumor growth. Conclusions: Overall, our results suggest that TTR has a potential anti-tumor effect in human NSCLC progression, which provides theoretical basis for the diagnosis and treatment of NSCLC.Above all, further understanding of TTR was useful for clinical care.

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α-Tocomonoenol Is Bioavailable in Mice and May Partly Be Regulated by the Function of the Hepatic α-Tocopherol Transfer Protein

Molecules ◽

10.3390/molecules25204803 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4803

Author(s):

Andrea Irías-Mata ◽

Nadine Sus ◽

Maria-Lena Hug ◽

Marco Müller ◽

Walter Vetter ◽

...

Keyword(s):

Tissue Distribution ◽

Room Temperature ◽

Systemic Circulation ◽

Future Research ◽

Wild Type ◽

Transfer Protein ◽

In Vivo Experiments ◽

And Storage

Tocomonoenols are vitamin E derivatives present in foods with a single double bond at carbon 11’ in the sidechain. The α-tocopherol transfer protein (TTP) is required for the maintenance of normal α-tocopherol (αT) concentrations. Its role in the tissue distribution of α-11′-tocomonoenol (αT1) is unknown. We investigated the tissue distribution of αT1 and αT in wild-type (TTP+/+) and TTP knockout (TTP−/−) mice fed diets with either αT or αT1 for two weeks. αT1 was only found in blood, not tissues. αT concentrations in TTP+/+ mice were in the order of adipose tissue > brain > heart > spleen > lungs > kidneys > small intestine > liver. Loss of TTP function depleted αT in all tissues. αT1, contrary to αT, was still present in the blood of TTP−/− mice (16% of αT1 in TTP+/+). Autoclaving and storage at room temperature reduced αT and αT1 in experimental diets. In conclusion, αT1 is bioavailable, reaches the blood in mice, and may not entirely depend on TTP function for secretion into the systemic circulation. However, due to instability of the test compounds in the experimental diets, further in vivo experiments are required to clarify the role of TTP in αT1 secretion. Future research should consider compound stability during autoclaving of rodent feed.

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Binding of 63Ni(II) to Ultrafiltrable Constituents of Rabbit Serum In Vivo and In Vitro

Clinical Chemistry ◽

10.1093/clinchem/21.4.521 ◽

1975 ◽

Vol 21 (4) ◽

pp. 521-527 ◽

Cited By ~ 16

Author(s):

Noritake Asato ◽

Maria van Soestbergen ◽

F William Sunderman

Keyword(s):

Rabbit Serum ◽

Total Serum ◽

In Vivo Experiments ◽

The Mean ◽

Layer Chromatography ◽

In Vivo Administration ◽

Mean Concentration

Abstract Binding of 63Ni(Il) to ultrafiltrable constituents of rabbit serum was studied (a) after in vitro incubation (2 h, 37 °C) of rabbit serum with 63NiCl2 (10-100 µmol/liter), and (b) at intervals (0.25-2 h) after in vivo administration of 63NiCl2 (40-160 µmol/kg body wt, i.v.). Serum ultrafiltrates were fractionated by thin-layer chromatography, and the separated compounds made visible by autoradiography and by ninhydrin staining. Several (≃5) ultrafiltrable 63Ni-complexes were demonstrable as distinct radiodense 63Ni-bands with chromatographic mobilities corresponding to those of ninhydrin-positive bands. Unbound 63Ni(II) was not detected in serum ultrafiltrates in either the in vitro or in vivo experiments. In sera (n = 10) incubated in vitro with 63Ni(II) (10 µmol/ liter), the mean percentage of ultrafiltrable 63Ni was 36% (range = 33-38) of total serum 63Ni. In contrast, in sera (n = 10) obtained 2 h after i.v. injection of 63Ni(II) (40 µmol/kg), the mean concentration of total serum 63Ni was 10.8 µmol/liter (range = 6-14), and the mean percentage of ultrafiltrable 63Ni was 15% (range = 9-21) of total serum 63Ni. The disparity between the percentages of ultrafiltrable 63Ni obtained in vitro and in vivo was obviated when the in vivo experiments were performed in rabbits bilaterally nephrectomized, with ligated common bile ducts. This investigation confirms the existence of several nickel receptors in serum ultrafiltrates and substantiates the role of ultrafiltrable complexes in the excretion of nickel.

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