Strain uses gap junctions to reverse stimulation of osteoblast proliferation by osteocytes

Identifying mechanisms by which cells of the osteoblastic lineage communicate in vivo is complicated by the mineralised matrix that encases osteocytes, and thus, vital mechanoadaptive processes used to achieve load‐bearing integrity remain unresolved. We have used the coculture of immunomagnetically purified osteocytes and primary osteoblasts from both embryonic chick long bone and calvariae to examine these mechanisms. We exploited the fact that purified osteocytes are postmitotic to examine both their effect on proliferation of primary osteoblasts and the role of gap junctions in such communication. We found that chick long bone osteocytes significantly increased basal proliferation of primary osteoblasts derived from an identical source (tibiotarsi). Using a gap junction inhibitor, 18β‐glycyrrhetinic acid, we also demonstrated that this osteocyte‐related increase in osteoblast proliferation was not reliant on functional gap junctions. In contrast, osteocytes purified from calvarial bone failed to modify basal proliferation of primary osteoblast, but long bone osteocytes preserved their proproliferative action upon calvarial‐derived primary osteoblasts. We also showed that coincubated purified osteocytes exerted a marked inhibitory action on mechanical strain–related increases in proliferation of primary osteoblasts and that this action was abrogated in the presence of a gap junction inhibitor. These data reveal regulatory differences between purified osteocytes derived from functionally distinct bones and provide evidence for 2 mechanisms by which purified osteocytes communicate with primary osteoblasts to coordinate their activity.     

Anther and pollen development:A conserved developmental pathway

Pollen development is a critical step in plant development that is needed for successful breeding and seed formation.Manipulation of male fertility has proved a useful trait for hybrid breeding and increased crop yield.However,although there is a good understanding developing of the molecular mechanisms of anther and pollen anther development in model species,such as Arabidopsis and rice,little is known about the equivalent processes in important crops.Nevertheless the onset of increased genomic information and genetic tools is facilitating translation of information from the models to crops,such as barley and wheat;this will enable increased understanding and manipulation of these pathways for agricultural improvement.     

Biochemical responses as early and reliable biomarkers of organophosphate and carbamate pesticides intoxication: A systematic literature review

Inhibition of cholinesterase (ChE) activity has been long considered as the main diagnostic method of organophosphate (OP) and carbamate pesticides poisoning; however, it has been shown that ChE activity may also be altered due to exposure to other non-organophosphorus toxicants and variety of different medical conditions. Hence, to avoid misdiagnosis, we aimed to systematically review available documents to look for additional biomarkers of OP and carbamate poisoning. The electronic databases in addition to Google scholar were searched for eligible articles on March 2022 using “organophosphate,” “carbamate,” and “biomarker” including all their similar terms. After collecting the relevant documents, the data were extracted and described qualitatively. In total, data of 66 articles from 51 human and 15 animal studies were extracted. Findings demonstrated that enzymes such as β-glucuronidase, neuropathy target esterase, amylase, and lipase, in addition to hematological indicators such as CBC, CRP, lactate dehydrogenase, and CPK have high sensitivity and accuracy in the diagnosis of OP poisoning. Findings suggest that using various markers for diagnosis of OP intoxication is helpful for appropriate management, and early identifying the patients at risk of death. The suggested biomarkers also help to avoid misdiagnosis of OP poisoning with other similar conditions.     

The role of miR-34 in cancer drug resistance

Resistance to conventional chemotherapy remains a major cause of cancer relapse and cancer-related deaths. Therefore, there is an urgent need to overcome resistance barriers. To improve cancer treatment approaches, it is critical to elucidate the basic mechanisms underlying drug resistance. Increasingly, the mechanisms involving micro-RNAs (miRNAs) are studied because miRNAs are also considered practical therapeutic options due to high degrees of specificity, efficacy, and accuracy, as well as their ability to target multiple genes at the same time. Years of research have firmly established miR-34 as a key tumor suppressor miRNA whose target genes are involved in drug resistance mechanisms. Indeed, numerous articles show that low levels of circulating miR-34 or tumor-specific miR-34 expression are associated with poor response to chemotherapy. In addition, elevation of inherently low miR-34 levels in resistant cancer cells effectively restores sensitivity to chemotherapeutic agents. Here, we review this literature, also highlighting some contradictory observations. In addition, we discuss the potential utility of miR-34 expression as a predictive biomarker for chemotherapeutic drug response. Although caution needs to be exercised, miR-34 is emerging as a biomarker that could improve cancer precision medicine.     

The effect of resistance level and stability demands on recruitment patterns and internal loading of spine in dynamic flexion and extension using a simple trunk model

The effects of external resistance on the recruitment of trunk muscles in sagittal movements and the coactivation mechanism to maintain spinal stability were investigated using a simple computational model of iso-resistive spine sagittal movements. Neural excitation of muscles was attained based on inverse dynamics approach along with a stability-based optimisation. The trunk flexion and extension movements between 60° flexion and the upright posture against various resistance levels were simulated. Incorporation of the stability constraint in the optimisation algorithm required higher antagonistic activities for all resistance levels mostly close to the upright position. Extension movements showed higher coactivation with higher resistance, whereas flexion movements demonstrated lower coactivation indicating a greater stability demand in backward extension movements against higher resistance at the neighbourhood of the upright posture. Optimal extension profiles based on minimum jerk, work and power had distinct kinematics profiles which led to recruitment patterns with different timing and amplitude of activation.