Spermatogenesis is the cellular process by which spermatogonia develop into mature spermatids within seminiferous tubules, the functional unit of the mammalian testis, under the structural and ...nutritional support of Sertoli cells and the precise regulation of endocrine factors. As germ cells develop, they traverse the seminiferous epithelium, a process that involves restructuring of Sertoli-germ cell junctions, as well as Sertoli-Sertoli cell junctions at the blood-testis barrier. The blood-testis barrier, one of the tightest tissue barriers in the mammalian body, divides the seminiferous epithelium into 2 compartments, basal and adluminal. The blood-testis barrier is different from most other tissue barriers in that it is not only comprised of tight junctions. Instead, tight junctions coexist and cofunction with ectoplasmic specializations, desmosomes, and gap junctions to create a unique microenvironment for the completion of meiosis and the subsequent development of spermatids into spermatozoa via spermiogenesis. Studies from the past decade or so have identified the key structural, scaffolding, and signaling proteins of the blood-testis barrier. More recent studies have defined the regulatory mechanisms that underlie blood-testis barrier function. We review here the biology and regulation of the mammalian blood-testis barrier and highlight research areas that should be expanded in future studies.
The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. It divides the seminiferous epithelium into the basal and the apical (adluminal) compartments. ...Meiosis I and II, spermiogenesis, and spermiation all take place in a specialized microenvironment behind the BTB in the apical compartment, but spermatogonial renewal and differentiation and cell cycle progression up to the preleptotene spermatocyte stage take place outside of the BTB in the basal compartment of the epithelium. However, the BTB is not a static ultrastructure. Instead, it undergoes extensive restructuring during the seminiferous epithelial cycle of spermatogenesis at stage VIII to allow the transit of preleptotene spermatocytes at the BTB. Yet the immunological barrier conferred by the BTB cannot be compromised, even transiently, during the epithelial cycle to avoid the production of antibodies against meiotic and postmeiotic germ cells. Studies have demonstrated that some unlikely partners, namely adhesion protein complexes (e.g., occludin-ZO-1, N-cadherin-β-catenin, claudin-5-ZO-1), steroids (e.g., testosterone, estradiol-17β), nonreceptor protein kinases (e.g., focal adhesion kinase, c-Src, c-Yes), polarity proteins (e.g., PAR6, Cdc42, 14-3-3), endocytic vesicle proteins (e.g., clathrin, caveolin, dynamin 2), and actin regulatory proteins (e.g., Eps8, Arp2/3 complex), are working together, apparently under the overall influence of cytokines (e.g., transforming growth factor-β3, tumor necrosis factor-α, interleukin-1α). In short, a "new" BTB is created behind spermatocytes in transit while the "old" BTB above transiting cells undergoes timely degeneration, so that the immunological barrier can be maintained while spermatocytes are traversing the BTB. We also discuss recent findings regarding the molecular mechanisms by which environmental toxicants (e.g., cadmium, bisphenol A) induce testicular injury via their initial actions at the BTB to elicit subsequent damage to germ-cell adhesion, thereby leading to germ-cell loss, reduced sperm count, and male infertility or subfertility. Moreover, we also critically evaluate findings in the field regarding studies on drug transporters in the testis and discuss how these influx and efflux pumps regulate the entry of potential nonhormonal male contraceptives to the apical compartment to exert their effects. Collectively, these findings illustrate multiple potential targets are present at the BTB for innovative contraceptive development and for better delivery of drugs to alleviate toxicant-induced reproductive dysfunction in men.
Spermatogenesis is supported by intricate crosstalk between Sertoli cells and germ cells including spermatogonia, spermatocytes, haploid spermatids, and spermatozoa, which takes place in the ...epithelium of seminiferous tubules. Sertoli cells, also known as ‘mother’ or ‘nurse’ cells, provide nutrients, paracrine factors, cytokines, and other biomolecules to support germ cell development. Sertoli cells facilitate the generation of several biologically active peptides, which include F5-, noncollagenous 1 (NC1)-, and laminin globular (LG)3/4/5-peptide, to modulate cellular events across the epithelium. Here, we critically evaluate the involvement of these peptides in facilitating crosstalk between Sertoli and germ cells to support spermatogenesis and thus fertility. Modulating or mimicking the activity of F5-, NC1-, and LG3/4/5-peptide could be used to enhance the transport across the blood–testis barrier (BTB) of contraceptive drugs or to treat male infertility.
The testis produces three endogenous regulatory bioactive peptides known as F5-, NC1-, and LG3/4/5-peptide to modulate blood–testis barrier (BTB) and spermatogenic functions.F5- and NC1-peptide promote BTB remodeling by making the barrier ‘leaky’ and facilitate the degeneration of adhesion sites at the Sertoli–spermatid interface known as the apical ectoplasmic specialization (ES), to support the transport of preleptotene spermatocytes across the immunological barrier and the release of sperm at spermiation.LG3/4/5-peptide, however, promotes BTB function by making the barrier ‘tighter’, and promotes spermatid adhesion in the testis.These three bioactive peptides thus serve as molecular switches that can turn various cellular events ‘on’ or ‘off’ during the epithelial cycle of spermatogenesis.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Graphitic carbon nitride (g-C3N4) and boron-doped g-C3N4 were prepared by heating melamine and the mixture of melamine and boron oxide, respectively. X-ray diffraction, X-ray photoelectron ...spectroscopy, and UV−vis spectra were used to describe the properties of as-prepared samples. The electron paramagnetic resonance was used to detect the active species for the photodegradation reaction over g-C3N4. The photodegradation mechanisms for two typical dyes, rhodamine B (Rh B) and methyl orange (MO), are proposed based on our comparison experiments. In the g-C3N4 photocatalysis system, the photodegradation of Rh B and MO is attributed to the direct hole oxidation and overall reaction, respectively; however, for the MO photodegradation the reduction process initiated by photogenerated electrons is a major photocatalytic process compared with the oxidation process induced by photogenerated holes. Boron doping for g-C3N4 can promote photodegradation of Rh B because the boron doping improves the dye adsorption and light absorption of catalyst.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
The g-C3N4 photocatalyst was synthesized by directly heating the low-cost melamine. The methyl orange dye (MO) was selected as a photodegrading goal to evaluate the photocatalytic activity of ...as-prepared g-C3N4. The comparison experiments indicate that the photocatalytic activity of g-C3N4 can be largely improved by the Ag loading. The strong acid radical ion (SO4 2− or NO3 −) can promote the degrading rate of MO for g-C3N4 photocatalysis system. The MO degradation over the g-C3N4 is mainly attributed to the photoreduction process induced by the photogenerated electrons. Our results clearly indicate that the metal-free g-C3N4 has good performance in photodegradation of organic pollutant.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Plastic film mulching has played an important role in Chinese agriculture due to its soil warming and moisture conservation effects. With the help of plastic film mulch technology, grain and cash ...crop yields have increased by 20-35% and 20-60%, respectively. The area of plastic film coverage in China reached approximately 20 million hectares, and the amount of plastic film used reached 1.25 million tons in 2011. While producing huge benefits, plastic film mulch technology has also brought on a series of pollution hazards. Large amounts of residual plastic film have detrimental effects on soil structure, water and nutrient transport and crop growth, thereby disrupting the agricultural environment and reducing crop production. To control pollution, the Chinese government urgently needs to elevate plastic film standards. Meanwhile, research and development of biodegradable mulch film and multi-functional mulch recovery machinery will help promote effective control and management of residual mulch pollution.
While remdesivir has garnered much hope for its moderate anti-Covid-19 effects, its parent nucleoside, GS-441524, has been overlooked. Pharmacokinetic analysis of remdesivir evidences premature serum ...hydrolysis to GS-441524; GS-441524 is the predominant metabolite reaching the lungs. With its synthetic simplicity and in vivo efficacy in the veterinary setting, we contend that GS-441524 is superior to remdesivir for Covid-19 treatment.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM, UPUK
To evaluate a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and compare it with RT-PCR.
...We designed primers specific to the orf1ab and S genes of SARS-CoV-2. Total viral RNA was extracted using the QIAamp Viral RNA Mini Kit. We optimized the RT-LAMP assay, and evaluated it for its sensitivity and specificity of detection using real-time turbidity monitoring and visual observation.
The primer sets orf1ab-4 and S-123 amplified the genes in the shortest times, the mean (±SD) times were 18 ± 1.32 min and 20 ± 1.80 min, respectively, and 63°C was the optimum reaction temperature. The sensitivities were 2 × 101 copies and 2 × 102 copies per reaction with primer sets orf1ab-4 and S-123, respectively. This assay showed no cross-reactivity with 60 other respiratory pathogens. To describe the availability of this method in clinical diagnosis, we collected 130 specimens from patients with clinically suspected SARS-CoV-2 infection. Among them, 58 were confirmed to be positive and 72 were negative by RT-LAMP. The sensitivity was 100% (95% CI 92.3%–100%), specificity 100% (95% CI 93.7%–100%). This assay detected SARS-CoV-2 in a mean (±SD) time of 26.28 ± 4.48 min and the results can be identified with visual observation.
These results demonstrate that we developed a rapid, simple, specific and sensitive RT-LAMP assay for SARS-CoV-2 detection among clinical samples. It will be a powerful tool for SARS-CoV-2 identification, and for monitoring suspected patients, close contacts and high-risk groups.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The use of adult stem cells is limited by the quality and quantity of host stem cells. It has been demonstrated that Wharton's jelly-derived mesenchymal stem cells (WJMSCs), a primitive stromal ...population, could integrate into ischemic cardiac tissues and significantly improve heart function. In this randomized, controlled trial, our aim was to assess the safety and efficacy of intracoronary WJMSCs in patients with ST-elevation acute myocardial infarction (AMI).
In a multicenter trial, 116 patients with acute ST-elevation MI were randomly assigned to receive an intracoronary infusion of WJMSCs or placebo into the infarct artery at five to seven days after successful reperfusion therapy. The primary endpoint of safety: the incidence of adverse events (AEs) within 18 months, was monitored and quantified. The endpoint of efficacy: the absolute changes in myocardial viability and perfusion of the infarcted region from baseline to four months, global left ventricular ejection fraction (LVEF) from baseline to 18 months were measured using F-18-fluorodeoxyglucose positron emission computed tomography (F-18-FDG-PET) and 99mTc-sestamibi single-photon emission computed tomography (99mTc-SPECT), and two-dimensional echocardiography, respectively.
During 18 months follow-up, AEs rates and laboratory tests including tumor, immune, and hematologic indexes were not different between the two groups. The absolute increase in the myocardial viability (PET) and perfusion within the infarcted territory (SPECT) was significantly greater in the WJMSC group 6.9 ± 0.6 % (95 %CI, 5.7 to 8.2) and 7.1 ± 0.8 % (95 %CI, 5.4 to 8.8) than in the placebo group 3.3 ± 0.7 % (95 %CI, 1.8 to 4.7), P <0.0001 and 3.9 ± 0.6(95 %CI, 2.8 to 5.0), P = 0.002 at four months. The absolute increase in the LVEF at 18 months in the WJMSC group was significantly greater than that in the placebo group 7.8 ± 0.9 (6.0 to approximately 9.7) vs. 2.8 ± 1.2 (0.4 to approximately 5.1), P = 0.001. Concomitantly, the absolute decreases in LV end-systolic volumes and end-diastolic volumes at 18 months in the WJMSC group were significantly greater than those in the placebo group (P = 0.0004, P = 0.004, respectively).
Intracoronary infusion of WJMSCs is safe and effective in patients with AMI, providing clinically relevant therapy within a favorable time window. This study encourages additional clinical trials to determine whether WJMSCs may serve as a novel alternative to BMSCs for cardiac stem cell-based therapy.
Clinical Trials NCT01291329 (02/05/2011).
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
