Probiotics Supplements Improve the Sarcopenia-Related Quality of Life in Older Adults with Age-Related Muscle Decline.

A pathological increase in intestinal leak is implicated in age-associated muscle loss, termed sarcopenia, and reduced sarcopenia-related quality-of-life (SarQoL). However, the potential therapies remain elusive. We investigated the effects of probiotic supplementation on sarcopenia and SarQoL in geriatric older adults. We randomized sarcopenic men into placebo (age = 71.4 ± 3.9 years, n = 63) and probiotic (age = 73 ± 4.1 years, n = 60) groups for 16 weeks. The probiotic used was one capsule daily of Vivomix 112 billion for 16 weeks. We measured sarcopenia parameters of handgrip strength (HGS) and skeletal mass index (SMI), plasma zonulin (marker of the intestinal leak), and SarQoL using a targeted questionnaire. Probiotics improved the SarQoL scores for locomotion, functionality, and activities of daily living and prevented a decline in cumulative SarQoL observed in the placebo group (all p < 0.05). Probiotic supplementation also reduced plasma zonulin and marker of systemic bacterial load. These changes were accompanied by an increase in HGS and maintenance of gait speed in the probiotic group compared to the placebo group. Correlation analysis revealed significant associations of cumulative SarQoL scores with plasma zonulin and HGS in the probiotic group. Collectively, probiotics improved SarQoL and HGS by repairing pathological intestinal leak. Future studies may further dissect the relation between intestinal leak and SarQoL in older adults taking probiotics.

Metformin Improves Sarcopenia-Related Quality of Life in Geriatric Adults: A Randomized Controlled Trial.

OBJECTIVES: Metformin protects against age-related muscle decline, termed sarcopenia. However, the effects on sarcopenia quality-of-life (SarQoL) are unknown. We investigated the effects of metformin on SarQoL and associated mechanisms in older adults. METHOD: This double-blind randomized, placebo-controlled trial included geriatric adult men, divided into non-sarcopenic controls (age = 72.2 ± 4.3 years, n = 52) and two groups of patients with sarcopenia randomized into placebo (age at baseline = 74.4 ± 5.7 years, n = 54) and metformin (age at baseline = 71.2 ± 3.9 years, n = 47) groups. Patients in the metformin group received 1.7 grams twice daily for four months. We evaluated SarQoL, handgrip strength (HGS), plasma zonulin, c-reactive protein (CRP), and 8-isoprostanes. RESULTS: Patients with sarcopenia had lower HGS and SarQoL than controls (both p <0.05). Metformin improved the HGS and the SarQoL domains related to physical and mental health, locomotion, and leisure activities, as well as cumulative SarQoL scores (all p <0.05). Metformin also prevented the decline in the SarQoL domains for functionality and fear. Among plasma biomarkers, metformin reduced the levels of zonulin, CRP, 8-isoprostanes, and creatine kinase. We also found a significant correlation of plasma zonulin with cumulative SarQoL in patients with sarcopenia taking metformin, suggesting a role for intestinal repair in improving SarQoL. Finally, metformin did not affect body composition and gait speed. CONCLUSION: Overall, metformin improved HGS and SarQoL by repairing intestinal leakage. Our data have clinical relevance for improving the quality of life in older adults with sarcopenia.

Effect of asiatic acid supplementation in tris-extender on post-thaw functional competence, antioxidant enzyme activity and in vivo fertility of bull sperm.

Reactive oxygen species at supra-physiological levels trigger oxidative stress during cryopreservation, which can be neutralised by incorporating suitable antioxidants into the semen extender medium. This study was intended to explore the effect of asiatic acid (AA) as an antioxidant in semen extender on frozen-thawed sperm quality and in vivo fertility of bull sperm. Semen was collected from Holstein Friesian bulls for 10 consecutive weeks (total ejaculates = 60). Semen was cryopreserved with a Tris citric acid egg yolk-based extender supplemented with 0 (control), 20, 40, 60, and 100 µM AA. The supplementation of the extender with 40 and 60 µM AA improved (p < 0.05) post-thaw motility kinematics, plasma membrane integrity, acrosome integrity, sperm viability, and DNA integrity of bull sperm. Mitochondrial membrane potential was high (p < 0.05) with 60 µM of AA concentration in extender media. The catalase activity in seminal plasma was maintained (p < 0.05) when semen was added with 20, 40, and 60 µM of AA. The in vivo fertility was found to be significantly high with the semen extended with 60 µM AA. Conclusively, this study showed that AA supplementation in semen extender significantly improved sperm motility kinematics and cell integrity, conserved antioxidant enzyme activity, and improved in vivo fertility.

The 25-hydroxyvitamin D level in Kidney Transplant Recipients and Its Association With Renal Function and Other Cardio-Metabolic Risk Markers.

BACKGROUND: Vitamin D is the main hormone that plays a critical role in controlling mineral homeostasis. Transplant recipients frequently have altered levels of 25-hydroxyvitamin D (25[OH] D) and 1, 25-hydroxyvitamin (1, 25[OH] D). OBJECTIVES: To explore the status of vitamin D level in renal allograft recipients and its association with renal function and cardio-metabolic risk markers. METHODS: One hundred two adult kidney transplant recipients (KTRs) were included. Clinical history and information about transplantation and immunosuppression were recorded. Blood and urine samples were collected for relevant laboratory tests, including chronic kidney disease (CKD)-mineral and bone disorder markers (Ca, PO4, and 25[OH] D). RESULTS: The mean age was 35 ± 8 years, with a male/female ratio of 89/11%. The transplant duration was 34 ± 26 (4.5-112) months. All donors involved were living-related: fathers comprised 44%, wives 16%, sisters 13%, mothers 11%, and the others 16% (ie, brothers, sons, daughters, uncles, aunts). The immunosuppression regimen included prednisolone and tacrolimus in all, with mycophenolate mofetil in 96%. The estimated glomerular filtration rate showed CKD distribution from stage 1 to 5 in 6%, 29%, 44%, 15%, and 6%, respectively. Vitamin D level was lower in 22% (<20 ng/mL), insufficient (20-30 ng/mL) in 48%, and adequate (>30 ng/mL) in 30%. We compared different clinical and laboratory variables in 3 different vitamin D groups but found no difference in cardio-renal risk factors (P = Not Significant). Similarly, no correlation was seen between vitamin D levels and other clinical and metabolic factors. CONCLUSION: According to conventional cutoffs, the vitamin D (25[OH] D) level is inadequate in 70% of renal allograft recipients. The hormone level has no apparent association with renal function and major cardio-metabolic risk factors.

The Complexity of Skeletal Transverse Dimension: From Diagnosis, Management, and Treatment Strategies to the Application of Collaborative Cross (CC) Mouse Model.

This study investigates the significance of skeletal transverse dimension (STD) in orthodontic therapy and its impact on occlusal relationships. The primary goal is to enhance understanding and promote the integration of transverse skeletal diagnostics into routine orthodontic assessments. To achieve this aim, the study employs a comprehensive approach, utilizing model analysis, clinical assessments, radiographic measurements, and occlusograms. The initial step involves a meticulous assessment of deficiencies in the maxilla, mainly focusing on transverse dimension issues. Various successful diagnostic methods are employed to ascertain the type and presence of these deficiencies. Furthermore, the study compares surgically assisted maxillary expansion (SARME) and orthopedic maxillary expansion (OME) in addressing skeletal transverse issues. Stability assessments and efficacy analyses are conducted to provide valuable insights into the superiority of SARME over OME. The findings reveal that proper evaluation of STD is crucial in orthodontic diagnosis, as overlooking transverse dimension issues can lead to complications such as increased masticatory muscle activity, occlusal interferences, and an elevated risk of gingival recession. Surgically assisted maxillary expansion emerges as a more stable solution than orthopedic methods. In conclusion, incorporating skeletal transverse diagnostics into routine orthodontic assessments is imperative for achieving optimal occlusal relationships and minimizing negative consequences on dentition, periodontium, and joints. The study emphasizes the significance of accurate three-dimensional assessments and recommends the consideration of SARME over OME for addressing skeletal transverse deficiencies. Finally, the Collaborative Cross (CC) mouse model is also a novel mouse model for studying complex traits. Exploring the Collaborative Cross mouse model opens avenues for future research, promising further insights into transverse skeletal issues in orthodontics.

Facile synthesis of manganese-hafnium nanocomposites for multimodal MRI/CT imaging and in vitro photodynamic therapy of colon cancer.

Precise diagnosis of complex and soft tumors is challenging, which limits appropriate treatment options to achieve desired therapeutic outcomes. However, multifunctional nano-sized contrast enhancement agents based on nanoparticles improve the diagnosis accuracy of various diseases such as cancer. Herein, a facile manganese-hafnium nanocomposites (Mn3O4-HfO2 NCs) system was designed for bimodal magnetic resonance imaging (MRI)/computed tomography (CT) contrast enhancement with a complimentary function of photodynamic therapy. The solvothermal method was used to fabricate NCs, and the average size of Mn3O4 NPs and Mn3O4-HfO2 NCs was about 7 nm and 15 nm, respectively, as estimated by TEM. Dynamic light scattering results showed good dispersion and high negative (-33 eV) zeta potential, indicating excellent stability in an aqueous medium. Mn3O4-HfO2 NCs revealed negligible toxic effects on the NCTC clone 929 (L929) and mouse colon cancer cell line (CT26), demonstrating promising biocompatibility. The synthesized Mn3O4-HfO2 NCs exhibit significant enhancement in T1-weighted magnetic resonance imaging (MRI) and X-ray computed tomography (CT), indicating the appropriateness for dual-modal MRI/CT molecular imaging probes. Moreover, ultra-small Mn3O4-HfO2 NCs show good relaxivities for MRI/CT. These nanoprobes Mn3O4-HfO2 NCs further possessed outstanding reactive oxygen species (ROS) generation ability under minute ultraviolet light (6 mW·cm-2) to ablate the colon cancer cells in vitro. Therefore, the designed multifunctional Mn3O4-HfO2 NCs were ideal candidates for cancer diagnosis and photodynamic therapy.

Spike structure of gold nanobranches induces hepatotoxicity in mouse hepatocyte organoid models.

BACKGROUND: Gold nanoparticles (GNPs) have been extensively recognized as an active candidate for a large variety of biomedical applications. However, the clinical conversion of specific types of GNPs has been hindered due to their potential liver toxicity. The origin of their hepatotoxicity and the underlying key factors are still ambiguous. Because the size, shape, and surfactant of GNPs all affect their properties and cytotoxicity. An effective and sensitive platform that can provide deep insights into the cause of GNPs' hepatotoxicity in vitro is therefore highly desired. METHODS: Here, hepatocyte organoid models (Hep-orgs) were constructed to evaluate the shape-dependent hepatotoxicity of GNPs. Two types of GNPs with different nanomorphology, gold nanospheres (GNSs) and spiny gold nanobranches (GNBs), were synthesized as the representative samples. Their shape-dependent effects on mice Hep-orgs' morphology, cellular cytoskeletal structure, mitochondrial structure, oxidative stress, and metabolism were carefully investigated. RESULTS: The results showed that GNBs with higher spikiness and tip curvature exhibited more significant cytotoxicity compared to the rounded GNSs. The spike structure of GNBs leads to a mitochondrial damage, oxidative stress, and metabolic disorder in Hep-orgs. Meanwhile, similar trends can be observed in HepG2 cells and mice models, demonstrating the reliability of the Hep-orgs. CONCLUSIONS: Hep-orgs can serve as an effective platform for exploring the interactions between GNPs and liver cells in a 3D perspective, filling the gap between 2D cell models and animal models. This work further revealed that organoids can be used as an indispensable tool to rapidly screen and explore the toxic mechanism of nanomaterials before considering their biomedical functionalities.

Identifying genetic susceptibility to Aspergillus fumigatus infection using collaborative cross mice and RNA-Seq approach.

BACKGROUND: Aspergillus fumigatus (Af) is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic background. The aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus (Af) using an RNAseq approach in CC lines and hepatic gene expression. METHODS: We studied 31 male mice from 25 CC lines at 8 weeks old; the mice were infected with Af. Liver tissues were extracted from these mice 5 days post-infection, and next-generation RNA-sequencing (RNAseq) was performed. The GENE-E analysis platform was used to generate a clustered heat map matrix. RESULTS: Significant variation in body weight changes between CC lines was observed. Hepatic gene expression revealed 12 top prioritized candidate genes differentially expressed in resistant versus susceptible mice based on body weight changes. Interestingly, three candidate genes are located within genomic intervals of the previously mapped quantitative trait loci (QTL), including Gm16270 and Stox1 on chromosome 10 and Gm11033 on chromosome 8. CONCLUSIONS: Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards Af. As a next step, eQTL analysis will be performed for our RNA-Seq data. Suggested candidate genes from our study will be further assessed with a human cohort with aspergillosis.

Dumbbell-shaped bimetallic AuPd nanoenzymes for NIR-II cascade catalysis-photothermal synergistic therapy.

The noble metal NPs that are currently applied to photothermal therapy (PTT) have their photoexcitation location mainly in the NIR-I range, and the low tissue penetration limits their therapeutic effect. The complexity of the tumor microenvironment (TME) makes it difficult to inhibit tumor growth completely with a single therapy. Although TME has a high level of H2O2, the intratumor H2O2 content is still insufficient to catalyze the generation of sufficient hydroxide radicals (‧OH) to achieve satisfactory therapeutic effects. The AuPd-GOx-HA (APGH) was obtained from AuPd bimetallic nanodumbbells modified by glucose oxidase (GOx) and hyaluronic acid (HA) for photothermal enhancement of tumor starvation and cascade catalytic therapy in the NIR-II region. The CAT-like activity of AuPd alleviates tumor hypoxia by catalyzing the decomposition of H2O2 into O2. The GOx-mediated intratumoral glucose oxidation on the one hand can block the supply of energy and nutrients essential for tumor growth, leading to tumor starvation. On the other hand, the generated H2O2 can continuously supply local O2, which also exacerbates glucose depletion. The peroxidase-like activity of bimetallic AuPd can catalyze the production of toxic ‧OH radicals from H2O2, enabling cascade catalytic therapy. In addition, the high photothermal conversion efficiency (η = 50.7 %) of APGH nanosystems offers the possibility of photothermal imaging-guided photothermal therapy. The results of cell and animal experiments verified that APGH has good biosafety, tumor targeting, and anticancer effects, and is a precious metal nanotherapeutic system integrating glucose starvation therapy, nano enzyme cascade catalytic therapy, and PTT therapy. This study provides a strategy for photothermal-cascade catalytic synergistic therapy combining both exogenous and endogenous processes. STATEMENT OF SIGNIFICANCE: AuPd-GOx-HA cascade nanoenzymes were prepared as a potent cascade catalytic therapeutic agent, which enhanced glucose depletion, exacerbated tumor starvation and promoted cancer cell apoptosis by increasing ROS production through APGH-like POD activity. The designed system has promising photothermal conversion ability in the NIR-II region, simultaneously realizing photothermal-enhanced catalysis, PTT, and catalysis/PTT synergistic therapy both in vitro and in vivo. The present work provides an approach for designing and developing catalytic-photothermal therapies based on bimetallic nanoenzymatic cascades.

Investigation of gadolinium doped manganese nano spinel ferrites via magnetic hypothermia therapy effect towards MCF-7 breast cancer.

Magnetic spinel ferrite nanoparticles (MSF-NPs) are potential candidates for biomedical applications, especially in cancer diagnosis and therapy due to their excellent physiochemical and magnetic properties. In the current study, MSF-NPs were fabricated by sol-gel auto combustion method. The crystal structure and surface morphology were confirmed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The magnetic properties were studied by VSM (vibrating sample magnetometer). As increasing Gd3+ concentration, the saturation magnetization values decreased from (17.8-2.3) emu/g, while the coercivity decreased from (499-133) Oe at room temperature. Finally, the fabricated MSF-NPs were tested against anticancer activity by MTT assay. The IC50 = 21.27 µg/mL value was observed, showing the strong antiproliferative activity of these nanoparticles. These results suggested that the obtained MSF-NPs would be useful for remote-controlled hyperthermia therapy for cancer treatment and MRI application due to their excellent magnetic properties. These distinct properties make MSF-NPs most suitable for cancer treatment and bright Contrast Agents (T1-MRI).

Tuning phase separation in DPPDTT/PMMA blend to achieve molecular self-assembly in the conducting polymer for organic field effect transistors.

The semiconductor/insulator blends for organic field-effect transistors are a potential solution to improve the charge transport in the active layer by inducing phase separation in the blends. However, the technique is less investigated for long-chain conducting polymers such as Poly[2,5-(2-octyldodecyl)-3,6-diketopyrrolopyrrole-alt-5,5-(2,5-di(thien-2-yl)thieno [3,2-b]thiophene)] (DPPDTT), and lateral phase separation is generally reported due to the instability during solvent evaporation, which results in degraded device performance. Herein, we report how to tailor the dominant mechanism of phase separation in such blends and the molecular assembly of the polymer. For DPPDTT/PMMA blends, we found that for higher DPPDTT concentrations (more than 75%) where the vertical phase separation mechanism is dominant, PMMA assisted in the self-assembly of DPPDTT to form nanowires and micro-transport channels on top of PMMA. The formation of nanowires yielded 13 times higher mobility as compared to pristine devices. For blend ratios with DPPDTT ≤ 50%, both the competing mechanisms, vertical and lateral phase separation, are taking place. It resulted in somewhat lower charge carrier mobilities. Hence, our results show that by systematic tuning of the blend ratio, PMMA can act as an excellent binding material in long-chain polymers such as DPPDTT and produce vertically stratified and aligned structures to ensure high mobility devices.

Detection of Constitutional Structural Variants by Optical Genome Mapping: A Multisite Study of Postnatal Samples.

Optical genome mapping is a high-resolution technology that can detect all types of structural variations in the genome. This second phase of a multisite study compares the performance of optical genome mapping and current standard-of-care methods for diagnostic testing of individuals with constitutional disorders, including neurodevelopmental impairments and congenital anomalies. Among the 627 analyses in phase 2, 405 were of retrospective samples supplied by five diagnostic centers in the United States and 94 were prospective samples collected over 18 months by two diagnostic centers (June 2021 to October 2022). Additional samples represented a family cohort to determine inheritance (n = 119) and controls (n = 9). Full concordance of results between optical genome mapping and one or more standard-of-care diagnostic tests was 98.6% (618/627), with partial concordance in an additional 1.1% (7/627).

Mapping novel QTL and fine mapping of previously identified QTL associated with glucose tolerance using the collaborative cross mice.

A chronic metabolic illness, type 2 diabetes (T2D) is a polygenic and multifactorial complicated disease. With an estimated 463 million persons aged 20 to 79 having diabetes, the number is expected to rise to 700 million by 2045, creating a significant worldwide health burden. Polygenic variants of diabetes are influenced by environmental variables. T2D is regarded as a silent illness that can advance for years before being diagnosed. Finding genetic markers for T2D and metabolic syndrome in groups with similar environmental exposure is therefore essential to understanding the mechanism of such complex characteristic illnesses. So herein, we demonstrated the exclusive use of the collaborative cross (CC) mouse reference population to identify novel quantitative trait loci (QTL) and, subsequently, suggested genes associated with host glucose tolerance in response to a high-fat diet. In this study, we used 539 mice from 60 different CC lines. The diabetogenic effect in response to high-fat dietary challenge was measured by the three-hour intraperitoneal glucose tolerance test (IPGTT) test after 12 weeks of dietary challenge. Data analysis was performed using a statistical software package IBM SPSS Statistic 23. Afterward, blood glucose concentration at the specific and between different time points during the IPGTT assay and the total area under the curve (AUC0-180) of the glucose clearance was computed and utilized as a marker for the presence and severity of diabetes. The observed AUC0-180 averages for males and females were 51,267.5 and 36,537.5 mg/dL, respectively, representing a 1.4-fold difference in favor of females with lower AUC0-180 indicating adequate glucose clearance. The AUC0-180 mean differences between the sexes within each specific CC line varied widely within the CC population. A total of 46 QTL associated with the different studied phenotypes, designated as T2DSL and its number, for Type 2 Diabetes Specific Locus and its number, were identified during our study, among which 19 QTL were not previously mapped. The genomic interval of the remaining 27 QTL previously reported, were fine mapped in our study. The genomic positions of 40 of the mapped QTL overlapped (clustered) on 11 different peaks or close genomic positions, while the remaining 6 QTL were unique. Further, our study showed a complex pattern of haplotype effects of the founders, with the wild-derived strains (mainly PWK) playing a significant role in the increase of AUC values.

A leaky gut contributes to reduced sarcopenia-related quality of life (SarQoL) in geriatric older adults.

PURPOSE: The sarcopenia quality-of-life (SarQoL) questionnaire is designed to evaluate the quality of life of sarcopenic patients. A pathological increase in intestinal permeability leads to several systemic diseases, but its contribution to SarQoL is unknown. METHODS: We recruited controls (n = 84, age = 74.6 ± 4.9 years) and sarcopenic (n = 55, age = 76.1 ± 4.2 years) men for validating and adapting a Pashto version of SarQoL. We measured the scores for seven domains of SarQoL, body composition, and handgrip strength (HGS). We also measured plasma zonulin as a marker of increased intestinal permeability. RESULTS: The Pashto SarQoL exhibited adequate discriminative ability, construct validity, internal consistency, and test-retest reliability, without exhibiting the floor and ceiling effect. Sarcopenic patients had higher plasma zonulin and lower scores on SarQoL domains for physical and mental health, locomotion, body composition, functionality, activities of daily living, leisure, and fear, and cumulative SarQoL scores than controls. Plasma zonulin exhibited significant coefficients of determination with Pashto SarQoL domains for locomotion (r2 = 0.217), functionality (r2 = 0.101), activities of daily living (r2 = 0.302), and cumulative SarQoL scores (r2 = 0.168). We also found high efficacies of zonulin in diagnosing low scores for functionality (AUC = 0.785, 95% C.I = 0.708-0.863), activities of daily living (AUC = 0.785, 95% C.I = 0.708-0.863), and cumulative SarQoL scores (AUC = 0.821, 95% C.I = 0.751-0.891). CONCLUSION: Altogether, SarQoL appears reliable in measuring the quality of life in sarcopenic patients. A leaky gut has a potential contribution to reduced SarQoL in sarcopenia.

Photosynthetic acclamatory response of Panicum antidotale Retz. populations to root zone desiccation stress / Reação fotossintética aclamatória de Panicum antidotale Retz. populações submetidas ao estresse da dessecação da zona radicular

Abstract Growth of plants is severely reduced due to water stress by affecting photosynthesis including photosystem II (PSII) activity and electron transport. This study emphasised on comparative and priority targeted changes in PSII activity due to progressive drought in seven populations of Panicum antidotale (P. antidotale) collected from Cholistan Desert and non-Cholistan regions. Tillers of equal growth of seven populations of P. antidotale grown in plastic pots filled with soil were subjected progressive drought by withholding water irrigation for three weeks. Progressive drought reduced the soil moisture content, leaf relative water content, photosynthetic pigments and fresh and dry biomass of shoots in all seven populations. Populations from Dingarh Fort, Dingarh Grassland and Haiderwali had higher growth than those of other populations. Cholistani populations especially in Dingarh Grassland and Haiderwali had greater ability of osmotic adjustment as reflected by osmotic potential and greater accumulation of total soluble proteins. Maximum H2O2 under water stress was observed in populations from Muzaffargarh and Khanewal but these were intermediate in MDA content. Under water stress, populations from Muzaffargarh and Dingarh Fort had greater K+ accumulation in their leaves. During progressive drought, non-Cholistani populations showed complete leaf rolling after 23 days of drought, and these populations could not withstand with more water stress condition while Cholistani populations tolerated more water stress condition for 31 days. Moreover, progressive drought caused PSII damages after 19 days and it became severe after 23 days in non-Cholistani populations of P. antidotale than in Cholistani populations.

Resumo O crescimento das plantas é severamente reduzido devido ao estresse hídrico, afetando a fotossíntese, incluindo a atividade do fotossistema II (PSII) e o transporte de elétrons. Este estudo enfatizou as mudanças comparativas e prioritárias na atividade do PSII devido à seca progressiva em sete populações de Panicum antidotale (P. antidotale) coletadas no Deserto do Cholistão e regiões fora do Cholistão. Perfilhos de igual crescimento de sete populações de P. antidotale cultivadas em vasos de plástico cheios de solo foram submetidos à seca progressiva, retendo a irrigação com água por três semanas. A seca progressiva reduziu o teor de umidade do solo, teor de água relativo nas folhas, pigmentos fotossintéticos e biomassa fresca e seca dos brotos em todas as sete populações. Populações de Dingarh Fort, Dingarh Grassland e Haiderwali tiveram maior crescimento do que as de outras populações. As populações de Cholistani, especialmente em Dingarh Grassland e Haiderwali, apresentaram maior capacidade de ajuste osmótico, refletido pelo potencial osmótico e maior acúmulo de proteínas solúveis totais. H2O2 máximo sob estresse hídrico foi observado em populações de Muzaffargarh e Khanewal, mas estas foram intermediárias no conteúdo de MDA. Sob estresse hídrico, as populações de Muzaffargarh e Dingarh Fort tiveram maior acúmulo de K+ em suas folhas. Durante a seca progressiva, as populações não cholistanesas mostraram rolagem completa das folhas após 23 dias de seca, e essas populações não conseguiram suportar mais condições de estresse hídrico, enquanto as populações cholistani toleraram mais condições de estresse hídrico por 31 dias. Além disso, a seca progressiva causou danos ao PSII após 19 dias e tornou-se severa após 23 dias em populações não cholistanesas de P. antidotale do que em populações cholistanesas.

Mutations in the bone morphogenetic protein 15 gene causing defective protein secretion in Cholistani infertile sheep / Mutações no gene da proteína morfogenética óssea 15 causadoras de defeitos na secreção proteica em ovelhas inférteis Cholistani

Naturally occurring mutations in morphogenetic protein 15 (BMP15) are associated with decreased ovulation rate (OR), litter size (LS), and sterility. It is of a great interest to elucidate BMP15 gene in Cholistani sheep breed to uplift socio-economic status and the knowledge of Cholistani sheep breeding in Southern Punjab, Pakistan. In our study, a total of 50 infertile Cholistani sheep aged between 2-6 years and having no blood relation were screened for BMP15 mutations. For this purpose, a high-quality DNA was extracted from the blood of sheep followed by primer designing, Polymerase Chain Reaction (PCR) amplification, DNA sequencing, and in silico analyses. Out of total 50 samples, 9 samples including case 1 (T3), case 2 (T8), case 3 (T17), case 4 (T22), case 5 (T25), case 6 (T33), case 7 (T40), case 8 (T44), and case 9 (T47) were found positive for a variety of already reported and novel BMP15 mutations. Further in silico analyses of the observed mutations have shown the functional impact of these mutations on different characteristics (molecular weight, theoretical PI, estimated half-life, instability index, sub-cellular localization, and 3D confirmation) of the encoded proteins, possibly altering the normal functionality. In a nutshell, findings of this study have confirmed the possible essential role of the BMP15 mutations in the infertility of the Cholistani sheep.

Mutações de ocorrência natural na proteína morfogenética 15 (BMP15) estão associadas à diminuição da taxa de ovulação (TO), tamanho da ninhada (TN) e esterilidade. Estudar a BMP15 na raça Cholistani para elevar o status socioeconômico e o conhecimento da criação de ovinos Cholistani no sul de Punjab, Paquistão. Em nosso estudo, 50 ovelhas Cholistani inférteis sem parentesco sanguíneo foram rastreadas para mutações BMP15. Para tanto, um DNA de alta qualidade foi extraído do sangue dessas ovelhas, seguido de concepção do primer, amplificação da reação em cadeia da polimerase (PCR), sequenciamento de DNA e análises in silico. Do total de 50 amostras, 9, incluindo caso 1 (T3), caso 2 (T8), caso 3 (T17), caso 4 (T22), caso 5 (T25), caso 6 (T33), caso 7 (T40), caso 8 (T44) e caso 9 (T47), foram consideradas positivas para uma variedade de mutações BMP15 novas e já relatadas. Mais análises in silico das mutações observadas mostraram o impacto funcional dessas mutações em diferentes características (peso molecular, PI teórico, meia-vida estimada, índice de instabilidade, localização subcelular e confirmação 3D) das proteínas codificadas, possivelmente alterando a funcionalidade normal. Nossos achados confirmaram o possível papel essencial das mutações BMP15 na infertilidade de ovelhas Cholistani.

Ethnomedicinal uses of plants for various diseases in the remote areas of Changa Manga Forest, Pakistan / Usos etnomedicinais de plantas para várias doenças nas áreas remotas da Floresta Changa Manga, Paquistão

This study aims at reporting the indigenous knowledge of the medicinal flora from the inhabitants of surroundings of the World's largest artificial planted forest "Changa Manga", Pakistan. Data were collected by direct interviews and group meetings from 81 inhabitants including 32 local healers having information regarding the use of indigenous medicinal plants over a period of one year. Different statistical tools were applied to analyze the data including Frequency citation (FC), Relative frequency citation (RFC), Use Value, Factor of informants consensus and fidelity level. This study reported 73 plant species belonging to 37 plant families and 46 genera. The majority of plant species belong to compositae family. The most commonly used medicinal plants were P. hysterophorus L., P. dactylifera L., S. indicum L, P. harmala L., P. emblica L., and A. indica A.Juss. The greatest number of species was used to cure gastrointestinal disorders. The highest fidelity level (68.18%) was of E. helioscopia to cure gastrointestinal disorders. Maximum fresh uses (17) were reported by C. dactylon (L.) Pars. While the highest number of species reporting fresh uses in similar number was 13. In this study, five novel plants are being reported for the first time in Pakistan for their ethnomedicinal worth. Our data reflect unique usage of the medicinal plants in the study area. The statistical tools used in the study proved useful in pointing the most important and disease category specific plants. High use value plant and the new reported medicinal plants might prove an important source of the isolation of pharmacologically active compounds.

Este estudo tem como objetivo relatar o conhecimento indígena sobre a flora medicinal dos habitantes do entorno da maior floresta artificial plantada do mundo, a Changa Manga, no Paquistão. Os dados foram coletados por meio de entrevistas diretas e reuniões em grupo de 81 habitantes, incluindo 32 curandeiros locais, com informações sobre o uso de plantas medicinais indígenas durante o período de um ano. Diferentes ferramentas estatísticas foram aplicadas para analisar os dados, incluindo citação de frequência (FC), citação de frequência relativa (RFC), valor de uso, fator de consenso dos informantes e nível de fidelidade. Este estudo relatou 73 espécies de plantas pertencentes a 37 famílias de plantas e 46 gêneros. A maioria das espécies de plantas pertence à família Compositae. As plantas medicinais mais utilizadas foram P. hysterophorus L., P. dactylifera L., S. indicum L., P. harmala L., P. emblica L. e A. indica A. Juss. O maior número de espécies foi usado para curar distúrbios gastrointestinais. O maior nível de fidelidade (68,18%) foi de E. helioscopia para cura de distúrbios gastrointestinais. Os usos máximos em fresco (17) foram relatados por C. dactylon (L.) Pars. enquanto o maior número de espécies relatando usos frescos em número semelhante foi de 13. Neste estudo, cinco novas plantas estão sendo relatadas pela primeira vez no Paquistão por seu valor etnomedicinal. Nossos dados refletem o uso exclusivo das plantas medicinais na área de estudo. As ferramentas estatísticas utilizadas no estudo mostraram-se úteis para apontar as plantas mais importantes e específicas da categoria de doença. Plantas de alto valor de uso e as novas plantas medicinais relatadas podem ser uma importante fonte de isolamento de compostos farmacologicamente ativos.